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Sample records for 90y 188re 177lu

  1. Monte Carlo Calculation of Radioimmunotherapy with (90)Y-, (177)Lu-, (131)I-, (124)I-, and (188)Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts.

    Science.gov (United States)

    Lucas, S; Feron, O; Gallez, B; Masereel, B; Michiels, C; Vander Borght, T

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like (131)I or (90)Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of (90)Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as (90)Y, (177)Lu, (131)I, (124)I, and (188)Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). (90)Y and (188)Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  2. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    Directory of Open Access Journals (Sweden)

    S. Lucas

    2015-01-01

    Full Text Available Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP and normal tissue complication probability (NTCP curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC. 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  3. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    Science.gov (United States)

    Lucas, S.; Feron, O.; Gallez, B.; Masereel, B.; Michiels, C.; Vander Borght, T.

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases. PMID:26136812

  4. (90) Y/(177) Lu-labelled Cetuximab immunoconjugates: radiochemistry optimization to clinical dose formulation.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Sarma, Haladhar Dev; Nair, K V Vimalnath; Rajeswari, Ardhi; Dash, Ashutosh

    2016-07-01

    Radiolabelled monoclonal antibodies (mAbs) are increasingly being utilized in cancer theranostics, which is a significant move toward tailored treatment for individual patients. Cetuximab is a recombinant, human-mouse chimeric IgG1 mAb that binds to the epidermal growth factor receptor with high affinity. We have optimized a protocol for formulation of clinically relevant doses (~2.22 GBq) of (90) Y-labelled Cetuximab and (177) Lu-labelled Cetuximab by conjugation of the mAb with a suitable bifunctional chelator, N-[(R)-2-amino-3-(paraisothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N″,N″-pentaacetic acid (CHX-A″-DTPA). The radioimmunoconjugates demonstrated reasonably high specific activity (1.26 ± 0.27 GBq/mg for (90) Y-CHX-A″-DTPA-Cetuximab and 1.14 ± 0.15 GBq/mg for (177) Lu-CHX-A″-DTPA-Cetuximab), high radiochemical purity (>95%) and appreciable in vitro stability under physiological conditions. Preliminary biodistribution studies with both (90) Y-CHX-A″-DTPA-Cetuximab and (177) Lu-CHX-A″-DTPA-Cetuximab in Swiss mice bearing fibrosarcoma tumours demonstrated significant tumour uptake at 24-h post-injection (p.i.) (~16%ID/g) with good tumour-to-background contrast. The results of the biodistribution studies were further corroborated by ex vivo Cerenkov luminescence imaging after administration of (90) Y-CHX-A″-DTPA-Cetuximab in tumour-bearing mice. The tumour uptake at 24 h p.i. was significantly reduced with excess unlabelled Cetuximab, suggesting that the uptake was receptor mediated. The results of this study hold promise, and this strategy should be further explored for clinical translation.

  5. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

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    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  6. Somatostatin-based radiopeptide therapy with [{sup 177}Lu-DOTA]-TOC versus [{sup 90}Y-DOTA]-TOC in neuroendocrine tumours

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    Romer, A.; Seiler, D.; Brunner, P.; Ng, Q.K.T.; Mueller-Brand, J. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Marincek, N.; Walter, M.A. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); Koller, M.T. [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); Maecke, H.R. [University Hospital Basel, Division of Radiochemistry, Basel (Switzerland); Rochlitz, C. [University Hospital Basel, Department of Oncology, Basel (Switzerland); Briel, M. [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton (Canada); Schindler, C. [University of Basel, Swiss Tropical and Public Health Institute, Basel (Switzerland)

    2014-02-15

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides {sup 90}Y or {sup 177}Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [{sup 90}Y-DOTA]-TOC or [{sup 177}Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [{sup 90}Y-DOTA]-TOC and 141 patients underwent 259 cycles of [{sup 177}Lu-DOTA]-TOC. The median survival after [{sup 177}Lu-DOTA]-TOC and after [{sup 90}Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [{sup 177}Lu-DOTA]-TOC over [{sup 90}Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [{sup 177}Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [{sup 177}Lu-DOTA]-TOC and [{sup 90}Y-DOTA]-TOC. Furthermore, [{sup 177}Lu-DOTA]-TOC was less haematotoxic than [{sup 90}Y-DOTA]-TOC. (orig.)

  7. Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

    Directory of Open Access Journals (Sweden)

    Johnnie J Orozco

    Full Text Available Radioimmunotherapy (RIT for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11 targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

  8. Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy

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    Seregni, E.; Maccauro, M.; Chiesa, C.; Pascali, C.; Lorenzoni, A.; Bogni, A.; Coliva, A.; Bombardieri, E. [Fondazione IRCCS Istituto Nazionale Tumori, Nuclear Medicine, Milan (Italy); Mariani, L.; Vullo, S.Lo [Fondazione IRCCS Istituto Nazionale Tumori, Statistics and Biometry Unit, Milan (Italy); Mazzaferro, V. [Fondazione IRCCS Istituto Nazionale Tumori, Surgery and Liver Transplantation, Milan (Italy); De Braud, F.; Buzzoni, R. [Fondazione IRCCS Istituto Nazionale Tumori, Medical Oncology, Milan (Italy); Milione, M. [Fondazione IRCCS Istituto Nazionale Tumori, Pathology Department, Milan (Italy)

    2014-02-15

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ({sup 90}Y) and a medium-energy beta/gamma emitter ({sup 177}Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [{sup 177}Lu]DOTA-TATE (5.55 GBq) and [{sup 90}Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [{sup 177}Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment The results of our study indicates that combined [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. (orig.)

  9. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re.

    NARCIS (Netherlands)

    Brouwers, A.H.; Eerd-Vismale, J.E.M. van; Frielink, C.; Oosterwijk, E.; Oyen, W.J.G.; Corstens, F.H.M.; Boerman, O.C.

    2004-01-01

    Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested the stability, biodistribution, and therapeutic efficacy of various radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with

  10. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re.

    NARCIS (Netherlands)

    Brouwers, A.H.; Eerd-Vismale, J.E.M. van; Frielink, C.; Oosterwijk, E.; Oyen, W.J.G.; Corstens, F.H.M.; Boerman, O.C.

    2004-01-01

    Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested the stability, biodistribution, and therapeutic efficacy of various radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with

  11. High clinical and morphologic response using {sup 90}Y-DOTA-octreotate sequenced with {sup 177}Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours

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    Kong, Grace; Callahan, Jason; Pattison, David A.; Akhurst, Tim; Eu, Peter [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); Hofman, Michael S. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Parkville (Australia); Michael, Michael [Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia)

    2017-03-15

    Bulky disease is an adverse prognostic factor for {sup 177}Lu-DOTA-octreotate ({sup 177}Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). {sup 90}Y-DOTA-octreotate ({sup 90}Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than {sup 177}Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of {sup 90}Y-DOTATATE followed by 2-3 cycles of {sup 177}Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq {sup 90}Y-DOTATATE, and 21 GBq {sup 177}Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with {sup 90}Y -DOTATATE followed by {sup 177}Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either

  12. Feasibility and utility of re-treatment with {sup 177}Lu-DOTATATE in GEP-NENs relapsed after treatment with {sup 90}Y-DOTATOC

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    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine Unit, Meldola, FC (Italy); Bodei, Lisa [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Ibrahim, Toni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); D' Errico, Vincenzo [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2015-12-15

    Peptide receptor radionuclide therapy (PRRT) is a valid therapy for grade 1/2 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Although a median progression-free survival (PFS) of more than 20 months is frequently observed, the majority of patients relapse after 2 - 3 years. In the present study, we investigated the use of low dosage re-treatment with {sup 177}Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with {sup 90}Y-DOTATOC (Y-PRRT). Upon tumour progression, 26 patients with a PFS of at least 12 months after Y-PRRT were consecutively enrolled in a phase II study of re-treatment with Lu-PRRT. All patients had preserved kidney and haematological parameters and received 14.8 - 18.5 GBq of Lu-PRRT in four or five cycles. The disease control rate (DCR), toxicity, PFS and prognostic factors were evaluated. Median total activity of Lu-PRRT was 16.5 GBq in five cycles. The DCR was 84.6 %, median PFS was 22 months (95 % CI 16 months - not reached) compared to 28 months (95 % CI 20 - 36 months) after Y-PRRT. Tumour burden and number of liver metastases were important prognostic factors. Toxicity was mild after Lu-PRRT re-treatment in the majority of patients, with only two patients with grade 2 and one with grade 3 bone marrow toxicity; one patient had grade 2 and one grade 3 renal toxicity. Patients with GEP-NEN who have previously responded to Y-PRRT are suitable candidates for Lu-PRRT re-treatment on progression. Although our sample size was limited, low-dosage Lu-PRRT was safe, and led to DCR and PFS rates comparable with those observed when Y-PRRT was used as primary treatment. (orig.)

  13. First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease.

    Science.gov (United States)

    Herrmann, Ken; Schottelius, Margret; Lapa, Constantin; Osl, Theresa; Poschenrieder, Andreas; Hänscheid, Heribert; Lückerath, Katharina; Schreder, Martin; Bluemel, Christina; Knott, Markus; Keller, Ulrich; Schirbel, Andreas; Samnick, Samuel; Lassmann, Michael; Kropf, Saskia; Buck, Andreas K; Einsele, Hermann; Wester, Hans-Juergen; Knop, Stefan

    2016-02-01

    Chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. Based on promising experiences with a radiolabeled CXCR4 ligand ((68)Ga-pentixafor) for diagnostic receptor targeting, (177)Lu- and (90)Y-pentixather were recently developed as endoradiotherapeutic vectors. Here, we summarize the first-in-human experience in 3 heavily pretreated patients with intramedullary and extensive extramedullary manifestations of multiple myeloma undergoing CXCR4-directed endoradiotherapy. CXCR4 target expression was demonstrated by baseline (68)Ga-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic (177)Lu-pentixather dosimetry was performed before (177)Lu-pentixather or (90)Y-pentixather treatment. Subsequently, patients underwent additional chemotherapy and autologous stem cell transplantation for bone marrow rescue. A remarkable therapeutic effect was visualized in 2 patients, who showed a significant reduction in (18)F-FDG uptake. CXCR4-targeted radiotherapy with pentixather appears to be a promising novel treatment option in combination with cytotoxic chemotherapy and autologous stem cell transplantation, especially for patients with advanced multiple myeloma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. Peptide receptor radionuclide therapy with {sup 90}Y/{sup 177}Lu-labelled peptides for inoperable head and neck paragangliomas (glomus tumours)

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    Puranik, Ameya D.; Kulkarni, Harshad R.; Singh, Aviral; Baum, Richard P. [Zentralklinik Bad Berka, THERANOSTICS Centre for Molecular Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Bad Berka (Germany)

    2015-07-15

    Head and neck paragangliomas (HNPGLs) are rare tumours arising from autonomic nervous system ganglia. Although surgery offers the best chance of complete cure, there is associated morbidity due to the crucial location of these tumours. Radiotherapy arrests tumour growth and provides symptomatic improvement, but has long-term consequences. These tumours express somatostatin receptors (SSTR) and hence peptide receptor radionuclide therapy (PRRT) is now a treatment option. We assessed the molecular, morphological and clinical responses of inoperable HNPGLs to PRRT. Nine patients with inoperable HNPGL assessed between June 2006 and June 2014 were included. Four patients had a solitary lesion, four had multifocal involvement and one had distant metastases (bone and lungs). The patients were treated with PRRT using {sup 90}Y/{sup 177}Lu-labelled peptides after positive confirmation of SSTR expression on {sup 68}Ga-DOTATOC PET/CT. All patients received two to four courses of PRRT. Subsequent serial imaging with {sup 68}Ga-DOTATOC PET/CT was carried out every 6 months to assess response to treatment. Clinical (symptomatic) response was also assessed. Based on molecular response (EORTC) criteria, four of the nine patients showed a partial molecular response to treatment seen as significant decreases in SUV{sub max}, accompanied by a reduction in tumour size. Five patients showed stable disease on both molecular and morphological criteria. Six out of nine patients were symptomatic at presentation with manifestations of cranial nerve involvement, bone destruction at the primary site and metastatic bone pain. Molecular responses were correlated with symptomatic improvement in four out of these six patients; while two patients showed small reductions in tumour size and SUV{sub max}. The three asymptomatic patients showed no new lesions or symptomatic worsening. PRRT was effective in all patients, with no disease worsening seen, either in the form of neurological symptoms or

  15. Evaluation of S-values and dose distributions for {sup 90}Y, {sup 131}I, {sup 166}Ho, and {sup 188}Re in seven lobes of the rat liver

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    Xie Tianwu; Liu Qian; Zaidi, Habib [Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074 (China) and Key Laboratory of Biomedical Photonics of Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074 (China); Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074 (China); Key Laboratory of Biomedical Photonics of Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074 (China) and Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland); Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland); Geneva Neuroscience Center, Geneva University, CH-1211 Geneva (Switzerland) and Department of Nuclear Medicine and Molecular Imaging, University Medical Center Gronigen, University of Groningen, 9700 RB Groningen (Netherlands)

    2012-03-15

    Purpose: Rats have been widely used in radionuclide therapy research for the treatment of hepatocellular carcinoma (HCC). This has created the need to assess rat liver absorbed radiation dose. In most dose estimation studies, the rat liver is considered as a homogeneous integrated target organ with a tissue composition assumed to be similar to that of human liver tissue. However, the rat liver is composed of several lobes having different anatomical and chemical characteristics. To assess the overall impact on rat liver dose calculation, the authors use a new voxel-based rat model with identified suborgan regions of the liver. Methods: The liver in the original cryosectional color images was manually segmented into seven individual lobes and subsequently integrated into a voxel-based computational rat model. Photon and electron particle transport was simulated using the MCNPX Monte Carlo code to calculate absorbed fractions and S-values for {sup 90}Y, {sup 131}I, {sup 166}Ho, and {sup 188}Re for the seven liver lobes. The effect of chemical composition on organ-specific absorbed dose was investigated by changing the chemical composition of the voxel filling liver material. Radionuclide-specific absorbed doses at the voxel level were further assessed for a small spherical hepatic tumor. Results: The self-absorbed dose for different liver lobes varied depending on their respective masses. A maximum difference of 3.5% was observed for the liver self-absorbed fraction between rat and human tissues for photon energies below 100 keV. {sup 166}Ho and {sup 188}Re produce a uniformly distributed high dose in the tumor and relatively low absorbed dose for surrounding tissues. Conclusions: The authors evaluated rat liver radiation doses from various radionuclides used in HCC treatments using a realistic computational rat model. This work contributes to a better understanding of all aspects influencing radiation transport in organ-specific radiation dose evaluation for

  16. Compartmental and dosimetric studies of anti-CD20 labelled with {sup 188}Re; Estudo compartimental e dosimetrico do Anti-CD20 marcado com {sup 188}Re

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    Kuramoto, Graciela Barrio

    2016-10-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β{sup -} emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β{sup -} emitters as {sup 131}I, {sup 90}Y, {sup 188}Re {sup 177}Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). {sup 188}Re (E{sub β} = 2.12 MeV; E{sub γ} = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, {sup 188}Re can be obtained from a radionuclide generator of {sup 188}W/{sup 188}Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical {sup 188}Re-Anti-CD20, where the radionuclide can be obtained from a generator system {sup 188}W/{sup 188}Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with {sup 188}Re with the marking of the antibody with {sup 90}Y, {sup 131}I, {sup 177}Lu and {sup 99m}Tc (for their similar chemical characteristics) and {sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for {sup 188}Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of {sup 188}Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β{sup -131}I-labeled anti CD20, {sup 177

  17. Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Erik; Ljungberg, Michael; Martensson, Linda; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik; Joensson, Bo-Anders [Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden)

    2012-07-15

    Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom

  18. Biokinetic study of free {sup 177}Lu in NIH mice

    Energy Technology Data Exchange (ETDEWEB)

    Villarreal Jimenez, V.; Crudo, J., E-mail: josierys@yahoo.com [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Rojo, A.M.; Deluca, G.M. [Autoridad Regulatoria Nuclear (ARN), Buenos Aires (Argentina)

    2008-07-01

    Full text: {sup 177}Lu has been identified, by the scientific community, as a radionuclide with interesting advantages compared with {sup 90}Y and other beta emitters used in nuclear medicine. This paper analyses the free {sup 177}Lu biokinetic behavior in NIH male mice from activity measurements performed by the Radiopharmacy Division of CNEA (Comision Nacional de Energia Atomica) in the frame of an IAEA (International Atomic Energy Agency) Coordinated Research Project. The study of experimental data is a previous condition that allows drawing the activity-time curves for organs and to know the biodistribution of {sup 177}Lu. The cumulated activity in organs of interest in NIH male mice are calculated and critical organs are identified. The organs selected for analysis in this paper are the liver, kidneys, spleen, stomach, intestine, lungs, skeleton and red marrow. The last one is estimated from the activity measured in blood based on a recognized method published by Sgouros (2000). The results has been extrapolated to human assuming the same biokinetic behaviour as mice being the applicability of the different extrapolation methods also discussed. The direct extrapolation from mice data was the method of election from a radiological protection point of view. The measurement procedures, the data processing, the extrapolation techniques and the analysis performed in this study will contribute as a basis for future research of this group in the area of antibodies and other radiopharmaceutical labeled with {sup 177}Lu. The cumulated activity calculated in each organ is relevant because it makes possible to perform the dose assessment through the application of appropriate dose coefficients. It is a necessary step in order to evaluate the toxicity risk that is required in a pre-clinical study. (author)

  19. Preparation and Preliminary Evaluation of 177Lu-EDTMP

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>The study on 177Lu labeled radiopharmaceuticals for cancer therapy is fast emerging as an important part of nuclear medicine. 177Lu-EDTMP is possible to be an effective radiopharmaceutical for pain

  20. Preparation and Biodistribution Evaluation in Mice of ~(177)Lu-DOTA-TOC

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The study of 177Lu labeled radiopharmaceuticals for cancer therapy is fast emerging as an important part of nuclear medicine. 177Lu-labelling of DOTA derivatized peptide DOTA-TOC (Tyr3-Octreotide) was carried out and biodistribution of 177Lu-DOTA-TOC in normal

  1. Primary standardization of a {sup 177}Lu solution; Padronizacao primaria de uma solucao de {sup 177}Lu

    Energy Technology Data Exchange (ETDEWEB)

    Iwahara, Akira; Silva, Carlos Jose da; Tauhata, Luiz; Oliveira, Estela Maria de, E-mail: iwahara@ird.gov.b, E-mail: carlos@ird.gov.b, E-mail: tauhata@ird.gov.b, E-mail: estela@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Rezende, Eduarda Alexandre, E-mail: eduarda@ird.gov.b [Centro Federal de Educacao Tecnologica de Quimica (CEFET), Nilopolis, RJ (Brazil)

    2009-07-01

    For the purpose to make available reliable standards of {sup 177}Lu to the users and producers, a radionuclide solution was standardized using the primary methods of coincidence 4{pi}{beta}(PC)-{gamma}(NaI(Tl)) and of 4{pi}{beta}(LS)-{gamma}(NaI(Tl)). The results presented a convergence in the range of evaluated uncertainties. The standard uncertainties were of the 0.50 and 0.74% for the anticoincidence and coincidence respectively

  2. {sup 188}Re-Labeled Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jae Min [Seoul National University, Seoul (Korea, Republic of)

    2001-10-01

    The search for an ideal radioisotope for radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays with a short physical half-life of 16.9 hr, {sup 188}Re is an excellent candidate for radiotherapy. Its applications include the irradiation of coronary artery to prevent restenosis, treatment of rheumatoid arthritis, treatment of peritoneal effusion. palliation of metastatic bone pain, and treatment of liver cancer.

  3. Production of {sup 177}Lu for targeted radionuclide therapy: Available options

    Energy Technology Data Exchange (ETDEWEB)

    Dah, Ashutosh [Isotope Production and Applications Division, Bhabha Atomic Research Centre (BARC), Mumbai (India); Pillai, Maroor Raghavan Ambikalmajan [Molecular Group of Companies. Kerala (India); Knapp, Furn F. Jr. [Medical Isotopes Program, Isotope Dept. Group, Oak Ridge National Laboratory (ORNL), Oak Ridge (United States)

    2015-06-15

    This review provides a comprehensive summary of the production of {sup 177}Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of {sup 177}Lu having the required quality for preparation of a variety of {sup 177}Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of {sup 177}Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. While both “direct” and “indirect” reactor production routes offer the possibility for sustainable {sup 177}Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. A broad understanding and discussion of the issues associated with {sup 177}Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of {sup 177}Lu-labeled radiopharmaceuticals, but also help future developments.

  4. Production of {sup 186}Re and {sup 188}Re, and synthesis of {sup 188}Re-DTPA

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kazuyuki; Motoishi, Shoji; Kobayashi, Katsutoshi; Izumo, Mishiroku [Department of Radioisotopes, Japan Atomic Energy Research Institute, Tokai, Ibaraki (Japan); Musdja, Muhammad Yanis

    1999-08-01

    Production of radioactive rhenium isotopes {sup 186}Re and {sup 188}Re, and synthesis of {sup 188}Re-DTPA have been studied. For {sup 186}Re, a production method by the {sup 185}Re(n, {gamma}) {sup 186}Re reaction in a reactor has been established. For {sup 188}Re, a production method by the double neuron capture reaction of {sup 186}W, which produces a {sup 188}W/{sup 188}Re generator, has been established. For synthesis of {sup 188}Re-DTPA, the optimum conditions, including pH, the amounts of regents and so on, have been determined. (author)

  5. [{sup 177}Lu]DOTA-anti-CD20: Labeling and pre-clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Audicio, Paola F., E-mail: paudicio@cin.edu.u [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Castellano, Gustavo, E-mail: gcas@famaf.unc.edu.a [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, 5016 Cordoba (Argentina); Tassano, Marcos R.; Rezzano, Maria E.; Fernandez, Marcelo [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Riva, Eloisa [Clinica Hematologica ' Prof. Dra. L. Diaz' , Hospital de Clinicas. Av. Italia. sn, Montevideo (Uruguay); Robles, Ana; Cabral, Pablo; Balter, Henia; Oliver, Patricia [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay)

    2011-07-15

    Anti-CD20 (Rituximab), a specific chimeric monoclonal antibody used in CD20-positive Non-Hodgkin's Lymphoma, was conjugated to a bifunctional quelate (DOTA) and radiolabeled with {sup 177}Lu through a simple method. [{sup 177}Lu]-DOTA-anti-CD20 was obtained with a radiochemical purity higher than 97%, and showed good chemical and biological stability, maintaining its biospecificity to CD20 antigens. Monte Carlo simulation showed high doses deposited on a spheroid tumor mass model. This method seems to be an appropriate alternative for the production of [{sup 177}Lu]-DOTA-anti-CD20 as therapeutic radiopharmaceutical.

  6. Development of 177Lu-phytate Complex for Radiosynovectomy

    Directory of Open Access Journals (Sweden)

    Hassan Yousefnia

    2013-05-01

    Full Text Available Objective(s: In this work a new possible agent for radiosynovectomy has been targeted for articular pain palliation. Materials and Methods: Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 1013 n.cm-2.s-1. The product was converted into chloride form which was further used for labeling of 177Lu-phytate complex and checked using ITLC (MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase. The complex stability and viscosity were checked in the final solution up to seven days. The prepared complex solution (100 µCi/100 µl was injected intra-articularly to male rat knee joint. Leakage of radioactivity from injection site and its distribution in organs were investigated up to seven days. Results: The complex was successfully prepared with high radiochemical purity (>99.9 %. Approximately, the whole injected dose has remained in injection site seven days after injection. Conclusion: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology

  7. Production of {sup 177}Lu at the new research reactor FRM-II: Irradiation yield of {sup 176}Lu(n,{gamma}){sup 177}Lu

    Energy Technology Data Exchange (ETDEWEB)

    Dvorakova, Z. [Institut fuer Radiochemie der Technischen Universitaet Muenchen, D-85748 Garching (Germany)], E-mail: nov@rad.chemie.tu-muenchen.de; Henkelmann, R.; Lin, X.; Tuerler, A. [Institut fuer Radiochemie der Technischen Universitaet Muenchen, D-85748 Garching (Germany); Gerstenberg, H. [ZWE FRM-II der Technischen, Universitaet Muenchen, D-85748 Garching (Germany)

    2008-02-15

    Due to its physical and chemical characteristics, {sup 177}Lu is a very attractive radionuclide for use in nuclear medicine. This paper introduces a method for a precise calculation of the irradiation yield of {sup 177}Lu produced by neutron activation of {sup 176}Lu in a nuclear reactor. The calculation is based on the Westcott convention which requires the knowledge of the neutron flux parameters. In this work, the neutron flux parameters of the new research reactor FRM-II (Garching, Germany) were determined and the stability of thermal neutron flux and thermal neutron flux temperature was monitored. The comparison of theoretically calculated and experimentally determined yield for {sup 176}Lu(n,{gamma}){sup 177}Lu reaction is presented.

  8. Synthesis of {sup 188}Re-DMSA complex using carrier-free {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kazuyuki; Izumo, Mishiroku [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Islam, M.S.

    1997-03-01

    The synthesis of rhenium-DMSA labelled compound using carrier-free {sup 188}Re from the {sup 188}W/{sup 188}Re generator has been carried out. Stannous chloride was used as the reducing agent for reduction of rhenium and ascorbic acid was used as an antioxidant in the reaction media. The dependence of the yield of Re-DMSA complex upon the concentration of reducing agent, pH, reaction time, anti-oxidant, carrier and temperature was investigated. Under optimum conditions, the yield of Re-DMSA complexes were more than 98% for the carrier-free as well as carrier-added {sup 188}Re. The stability of the Re-DMSA complexes at different pH and time were also investigated. It was found that the Re-DMSA complex was very stable and did not undergo any changes or decomposition with the changes of pH from its initial values even after 48 hours of pH change for carrier-free as well as carrier-added complexes. (author)

  9. A potencial theranostic agent for EGF-R expression tumors: (177)Lu-DOTA-nimotuzumab.

    Science.gov (United States)

    Calzada, Victoria; Zhang, Xiuli; Fernandez, Marcelo; Diaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Deutscher, Susan L; Balter, Henia; Quinn, Thomas P; Cabral, Pablo

    2012-10-01

    In this work Nimotuzumab (monoclonal antibody, recognizes the EGF-R) was radiolabeled with (177)Lu as a potential cancer therapy radiopharmaceutical. In-vitro cell binding studies and in-vivo biodistribution and imaging studies were performed to determine the radiochemical stability, targeting specificity and pharmacokinetics of the (177)Lu-labeled antibody. Nimotuzumab was derivatized with DOTA-NHS at room temperature for 2 hours. DOTA-Nimotuzumab was radiolabeled with (177)LuCl3 (15 MBq/mg) at 37°C for 1 h. The radiochemical purity was assessed by ITLC, silica gel and by RP-HPLC. Binding specificity studies were performed with EGF-R positive A431 human epithelial carcinoma and EGF-R negative MDA-MB-435 breast carcinoma cells. Biodistribution studies were performed in healthy female CD-1 mice at 1 h, 4 h, 24 h, and A431 xenografted nude mice at 10 min, 1 h, 4 h, 24 h, 48 h, and 96 h. SPECT-CT imaging studies were performed in A431 xenografted mice at 24 h post injection. DOTA-Nimotuzumab was efficiently labeled with (177) LuCl(3) at 37°C. The in vitro stability of labeled product was optimal over 24 h in buffered saline and mouse serum. Specific recognition of EGF-R by (177)Lu-DOTA-Nimotuzumab was observed in A431 cell binding studies. Biodistribution studies demonstrated increasing tumor uptake of (177)Lu-DOTA-Nimotuzumab over time, with tumor to muscle ratios of 6.26, 10.68, and 18.82 at 4 h, 24 h, and 96 h post injection. Imaging of A431 xenografted mice showed high uptake in the tumor. (177)Lu-DOTA-Nimotuzumab has the potential to be a promising therapy agent, which may be useful in the treatment of patients with EGF-R positive cancer.

  10. Potential therapeutic radiotracers: preparation, biodistribution and metabolic characteristics of 177Lu-labeled cyclic RGDfK dimer.

    Science.gov (United States)

    Shi, Jiyun; Liu, Zhaofei; Jia, Bing; Yu, Zilin; Zhao, Huiyun; Wang, Fan

    2010-06-01

    In this study, we reported the preparation and evaluation of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2 (RGD2 = E[c(RGDfK)](2)) as a potential therapeutic radiotracers for the treatment of integrin alpha(v)beta(3)-positive tumors. The BALB/c nude mice bearing the U87MG human glioma xenografts were used to evaluate the biodistribution characteristics and excretion kinetics of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2. It was found that there were no major differences in their lipophilicity and biodistribution characteristics, particularly at latter time points. A major advantage of using DTPA-Bz as the bifunctional chelator (BFC) was its high radiolabeling efficiency (fast and high yield radiolabeling) at room temperature. Using DOTA and DOTA-Bz as BFCs, the radiolabeling kinetics was slow, and heating at 100 degrees C and higher DOTA-conjugate concentration were needed for successful (177)Lu-labeling. Therefore, DTPA-Bz is an optimal BFC for routine preparation of (177)Lu-labeled cyclic RGDfK peptides, and (177)Lu-DTPA-Bz-RGD2 is worthy of further investigation for targeted radiotherapy of integrin alpha(v)beta(3)-positive tumors.

  11. 188W/188Re Generator System and Its Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    A. Boschi

    2014-01-01

    Full Text Available The 188Re radioisotope represents a useful radioisotope for the preparation of radiopharmaceuticals for therapeutic applications, particularly because of its favorable nuclear properties. The nuclide decay pattern is through the emission of a principle beta particle having 2.12 MeV maximum energy, which is enough to penetrate and destroy abnormal tissues, and principle gamma rays (Eγ=155 keV, which can efficiently be used for imaging and calculations of radiation dose. 188Re may be conveniently produced by 188W/188Re generator systems. The challenges related to the double neutron capture reaction route to provide only modest yield of the parent 188W radionuclide indeed have been one of the major issues about the use of 188Re in nuclear medicine. Since the specific activity of 188W used in the generator is relatively low (<185 GBq/g, the eluted Re188O4- can have a low radioactive concentration, often ineffective for radiopharmaceutical preparation. However, several efficient postelution concentration techniques have been developed, which yield clinically useful Re188O4- solutions. This review summarizes the technologies developed for the preparation of 188W/188Re generators, postelution concentration of the 188Re perrhenate eluate, and a brief discussion of new chemical strategies available for the very high yield preparation of 188Re radiopharmaceuticals.

  12. Toxicity of trastuzumab labeled {sup 177}Lu on MCF7 and SKBr3 cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Rajabi, Hossein, E-mail: hrajabi@modares.ac.i [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Hossein Babaei, Mohammad; Johari Daha, Fariba [Department of Radioisotope, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of)

    2010-10-15

    In this study, we labeled trastuzumab with {sup 177}Lu to synthesize a new radiopharmaceutical for therapy of breast cancer and at the first stage investigated its therapeutic effects on SKBr3 and MCF7 breast cancer cell lines. Trastuzumab-{sup 177}Lu showed very good in-vitro characteristics such as high radiochemical purity (91{+-}0.9%), good stability in PBS buffer (86{+-}2.3%) and blood serum (81{+-}2.7%) up to 96 h, appropriate immunoreactivity (85.4{+-}1.1%) and high cytotoxicity in HER2 expression cells. 5 fold increase in toxicity of trastuzumab-{sup 177}Lu was observed when compared with unlabeled trastuzumab on SKBr3 cells.

  13. Standardization and measurement of gamma-ray probability per decay of 177Lu.

    Science.gov (United States)

    Dias, Mauro S; Silva, Fabrício F V; Koskinas, Marina F

    2010-01-01

    The procedure followed by the Nuclear Metrology Laboratory (LMN), at the Nuclear and Energy Research Institute (IPEN), for the primary standardization of (177)Lu is described. This radionuclide is widely used in radiopharmacy due to its convenient half-life and emitted beta ray energies. The (177)Lu solution was supplied during an international comparison sponsored by BIPM in 2009 and the primary standardization has been accomplished by the 4pibeta-gamma coincidence method using a proportional counter in 4pi geometry coupled with two NaI(Tl) scintillation counters. The beta efficiency was varied by placing Collodion and aluminum absorbers over and under the radioactive source. The (177)Lu calibrated sources were also measured in a previously calibrated HPGe spectrometer, in order to obtain the emission probability per decay for the selected gamma-ray transitions. The experimental extrapolation curves were also compared with Monte Carlo simulations by means of code ESQUEMA developed at the LMN.

  14. [177Lu]Bz-DTPA-EGF: Preclinical characterization of a potential radionuclide targeting agent against glioma.

    Science.gov (United States)

    Sundberg, Asa Liljegren; Gedda, Lars; Orlova, Anna; Bruskin, Alexander; Blomquist, Erik; Carlsson, Jörgen; Tolmachev, Vladimir

    2004-04-01

    Patients with glioblastoma multiforme have a poor prognosis due to recurrences originating from spread cells. The use of radionuclide targeting might increase the chance of inactivating single tumor cells with minimal damage to surrounding healthy tissue. As a target, overexpressed epidermal growth factor receptors (EGFR) may be used. A natural ligand to EGFR, the epidermal growth factor (EGF) is an attractive targeting agent due to its low molecular weight (6 kDa) and high affinity for EGFR. 177Lu (T(1/2) = 6.7 days) is a radionuclide well suited for treatment of small tumor cell clusters, since it emits relatively low-energy beta particles. The goal of this study was to prepare and preclinically evaluate both in vitro and in vivo the [177Lu]Bz-DTPA-EGF conjugate. The conjugate was characterized in vitro for its cell-binding properties, and in vivo for its pharmacokinetics and ability to target EGFR. [177Lu]Bz-DTPA-EGF bound to cultured U343 glioblastoma cells with an affinity of 1.9 nM. Interaction with EGFR led to rapid internalization, and more than 70% of the cell-associated radioactivity was internalized after 30 minutes of incubation. The retention of radioactivity was good, with more than 65% of the 177Lu still cell-associated after 2 days. Biodistribution studies of i.v. injected [177Lu]Bz-DTPA-EGF in NMRI mice demonstrated a rapid blood clearance. Most of the radioactivity was found in the liver and kidneys. The liver uptake was receptor-mediated, since it could be significantly reduced by preinjection of unlabeled EGF. In conclusion, [177Lu]Bz-DTPA-EGF seems to be a promising candidate for locoregional treatment of glioblastoma due to its high binding affinity, low molecular weight, and ability to target EGFR in vivo.

  15. Evaluation of two intraoperative gamma detectors for assessment of (177)Lu activity concentration in vivo.

    Science.gov (United States)

    Sandblom, Viktor; Ståhl, Ingun; Olofsson Bagge, Roger; Forssell-Aronsson, Eva

    2017-12-01

    Patients with somatostatin receptor-expressing neuroendocrine tumours can be treated with intravenously administered (177)Lu-octreotate. Few patients are cured with the present protocol due to the current dose limitation of normal organs at risk, such as the kidneys. By locally administering (177)Lu-octreotate to the liver for the purpose of treating liver metastases, a substantially reduced absorbed dose to organs at risk could be achieved. The development of such a technique requires the capability of measuring the (177)Lu activity concentration in tissues in vivo. The aim of this study was to evaluate different performance parameters of two commercially available intraoperative gamma detectors in order to investigate whether intraoperative gamma detector measurements could be used to determine (177)Lu activity concentration in vivo. Measurements were made using different sources containing (177)Lu. Response linearity, sensitivity, spatial resolution and its depth dependence, organ thickness dependence of the measured count rate and tumour detectability were assessed for two intraoperative gamma detectors. The two detectors (a scintillation and a semiconductor detector) showed differences in technical performance. For example, the sensitivity was higher for the scintillation detector, while the spatial resolution was better for the semiconductor detector. Regarding organ thickness dependence and tumour detectability, similar results were obtained for both detectors, and even relatively small simulated tumours of low tumour-to-background activity concentration ratios could be detected. Acceptable results were obtained for both detectors, although the semiconductor detector proved more advantageous for our purpose. The measurements demonstrated factors that must be corrected for, such as organ thickness or dead-time effects. Altogether, intraoperative gamma detector measurements could be used to determine (177)Lu activity concentration in vivo.

  16. Esthesioneuroblastoma (olfactory neuroblastoma) treated with 111In-octreotide and 177Lu-DOTATATE PRRT.

    Science.gov (United States)

    Makis, William; McCann, Karey; McEwan, Alexander J B

    2015-04-01

    A 51-year-old man with a recurrent metastatic esthesioneuroblastoma (olfactory neuroblastoma) was referred for peptide receptor radionuclide therapy (PRRT). He received 4 treatments of 111In-octreotide over 8 months and 3 treatments of 177Lu-DOTATATE over 4 months, which helped alleviate his symptoms and improved his quality of life; however, the tumor ultimately progressed and he passed away shortly thereafter. PRRT with 111In-octreotide or 177Lu-DOTATATE could play a role in the management of esthesioneuroblastoma.

  17. Predicting the yield of {sup 177}Lu radionuclide produced by the cyclic irradiation technique

    Energy Technology Data Exchange (ETDEWEB)

    Odame Duodu, Godfred, E-mail: jogd14@yahoo.co [Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, P.O. Box LG80, Legon Accra (Ghana); Akaho, Edward H.K.; Serfor-Armah, Yaw [Ghana Atomic Energy Commission, P.O. Box LG80, Legon Accra (Ghana); Nyarko, Benjamin J.B. [National Nuclear Research Institute, Ghana Atomic Energy Commission, P.O. Box LG80, Legon Accra (Ghana); Afi Achoribo, Elom [Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, P.O. Box LG80, Legon Accra (Ghana)

    2011-03-15

    The feasibility study on the production of {sup 177}Lu radioisotope using a low power research reactor has been conducted. A reliable method for predicting the yield of {sup 177}Lu produced using the cyclic activation technique based on the Westcott formalism has been established. A specific activity of 243.24 mCi/g was obtained when a {sup 176}Lu{sub 2}O{sub 3} of natural abundance was irradiated for 4 h and decayed for 20 h for four cycles at GHARR-1 with a neutron flux of 5.0x10{sup 11} ncm{sup -2} s{sup -1}.

  18. Production of non carrier added (n.c.a.) {sup 177}Lu for radiopharmaceutical applications

    Energy Technology Data Exchange (ETDEWEB)

    Barkhausen, Christoph

    2011-09-06

    The goal of this dissertation was the development of a process to produce non carrier added {sup 177}Lu at the FRM II. For this purpose, preparative chromatographic methods were evaluated and applied. The highest quality of the nuclide which could only be achieved through a complex chemical process, has been already been proven by clinical studies to be very advantageous. The process has been built up in a hot cell as a semi-automated process and is now being adapted to the requirements of the 'Arzneimittelgesetz' in order to establish n.c.a. {sup 177}Lu as a pharmaceutical product.

  19. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice.

    NARCIS (Netherlands)

    Schoffelen, R.; Graaf, W.T.A. van der; Franssen, G.M.; Sharkey, R.M.; Goldenberg, D.M.; McBride, W.J.; Rossi, E.A.; Eek, A.; Oyen, W.J.G.; Boerman, O.C.

    2010-01-01

    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies in combination with a radiolabeled peptide reduces the radiation dose to normal tissues, especially the bone marrow. In this study, the optimization, therapeutic efficacy, and toxicity of PRIT of colon cancer with a (177)Lu-labeled pep

  20. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Kwekkeboom, D.J.; Bakker, W.H.; Kam, B.L.; Teunissen, J.J.M.; Kooij, P.P.M.; Jong, M. de [Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam (Netherlands); Herder, W.W. de; Feelders, R.A. [Department of Internal Medicine, Erasmus Medical Center, Rotterdam (Netherlands); Eijck, C.H.J. van [Department of Surgery, Erasmus Medical Center, Rotterdam (Netherlands); Srinivasan, A.; Erion, J.L. [Mallinckrodt Medical, St. Louis, Missouri (United States); Krenning, E.P. [Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam (Netherlands); Department of Internal Medicine, Erasmus Medical Center, Rotterdam (Netherlands)

    2003-03-01

    Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [{sup 90}Y-DOTA{sup 0},Tyr{sup 3}]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA{sup 0},Tyr{sup 3}]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA{sup 0},Tyr{sup 3}]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide {sup 177}Lu, it has proved very successful in achieving tumour regression in animal models. The effects of {sup 177}Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi {sup 177}Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours

  1. Skin dose saving of the staff in 90Y/177Lu peptide receptor radionuclide therapy with the automatic dose dispenser.

    Science.gov (United States)

    Fioroni, Federica; Grassi, Elisa; Giorgia, Cavatorta; Sara, Rubagotti; Piccagli, Vando; Filice, Angelina; Mostacci, Domiziano; Versari, Annibale; Iori, Mauro

    2016-10-01

    When handling Y-labelled and Lu-labelled radiopharmaceuticals, skin exposure is mainly due to β-particles. This study aimed to investigate the equivalent dose saving of the staff when changing from an essentially manual radiolabelling procedure to an automatic dose dispenser (ADD). The chemist and physician were asked to wear thermoluminescence dosimeters on their fingertips to evaluate the quantity of Hp(0.07) on the skin. Data collected were divided into two groups: before introducing ADD (no ADD) and after introducing ADD. For the chemist, the mean values (95th percentile) of Hp(0.07) for no ADD and ADD are 0.030 (0.099) and 0.019 (0.076) mSv/GBq, respectively, for Y, and 0.022 (0.037) and 0.007 (0.023) mSv/GBq, respectively, for Lu. The reduction for ADD was significant (t-test with Pisotopes. The relative differences before and after ADD collected for every finger were treated using the Wilcoxon test, proving a significantly higher reduction in extremity dose to each fingertip for Lu than for Y (Pmedical staff, the mean values of Hp(0.07) (95th percentile) for no ADD and ADD are 0.021 (0.0762) and 0.0143 (0.0565) mSv/GBq, respectively, for Y, and 0.0011 (0.00196) and 0.0009 (0.00263) mSv/GBq, respectively, for Lu. The t-test provided a P-value less than 0.05 for both isotopes, making the difference between ADD and no ADD significant. ADD positively affects the dose saving of the chemist in handling both isotopes. For the medical staff not directly involved with the introduction of the ADD system, the analysis shows a learning curve of the workers over a 5-year period. Specific devices and procedures allow staff skin dose to be limited.

  2. Preparation and Characterization of {sup 177}Lu Labeled Antibody against Tyrosine Kinase Receptor Her2

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Young; Hong, Young-Don; Choi, Sun-Ju [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-05-15

    The tyrosine kinase receptor Her2, also known in humans as erbB2, is a member of the epidermal growth factor receptor (EGFR or erbB1) family. The Her2 is highly expressed in many cancer types and over expressed in approximately 30% of all primary breast cancer. Overexpression of Her2 is associated with a poor prognosis. Her2 is a suitable target because it involves an extracellular domain that can be targeted by antibodies produced by B cells. Based on these advantages, we tried to prepare the {sup 177}Lu labeled Her2 antibody. This radioimmunoconjugate could act by not only blocking the Her2 signalling pathway using antibody but also killing the tumour cell using {beta} energy of {sup 177}Lu.

  3. Quantitative (177)Lu SPECT imaging using advanced correction algorithms in non-reference geometry.

    Science.gov (United States)

    D'Arienzo, M; Cozzella, M L; Fazio, A; De Felice, P; Iaccarino, G; D'Andrea, M; Ungania, S; Cazzato, M; Schmidt, K; Kimiaei, S; Strigari, L

    2016-12-01

    Peptide receptor therapy with (177)Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of (177)Lu in complex anthropomorphic geometry using advanced correction algorithms. Acquisitions were performed on the higher (177)Lu photopeak (208keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using μ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software. The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1). For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions. In conclusion, accurate activity quantification of (177)Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208keV photopeak using medium-energy collimators.

  4. In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate

    Directory of Open Access Journals (Sweden)

    Dale Bailey

    2016-01-01

    Full Text Available Objective(s:Lutetium-177 can be made with high specific activity and with no other isotopes of lutetium present, referred to as “No Carrier Added” (NCA 177Lu. We have radiolabelled DOTA-conjugated peptide DOTA‐(Tyr3‐octreotate with NCA 177Lu (“NCA-LuTATE” and used it in nearly 40 therapeutic administrations for subjects with neuroendocrine tumours or meningiomas. In this paper, we report on our initial studies on aspects of the biodistribution and dosimetry of NCA-LuTATE from gamma camera 2D whole body (WB and quantitative 3D SPECT (qSPECT 177Lu imaging. Methods: Thirteen patients received 39 NCA-LuTATE injections. Extensive WB planar and qSPECT imaging was acquired at approximately 0.5, 4, 24 and 96 h to permit estimates of clearance and radiation dose estimation using MIRD-based methodology (OLINDA-EXM. Results:The average amount of NCA-Lutate administered per cycle was 7839±520 MBq. Bi-exponential modelling of whole body clearance showed half lives for the fast & slow components of t½=2.1±0.6 h and t½=58.1±6.6 h respectively. The average effective dose to kidneys was 3.1±1.0 Gy per cycle. In eight patients completing all treatment cycles the average total dose to kidneys was 11.7±3.6 Gy. Conclusions: We have shown that NCA-LuTATE has an acceptable radiation safety profile and is a suitable alternative to Carrier-Added 177Lu formulations. The fast component of the radiopharmaceutical clearance was closely correlated with baseline renal glomerular filtration rate, and this had an impact on radiation dose to the kidneys. In addition, it has less radioactive waste issues and requires less peptide per treatment.

  5. {sup 177}Lu-DOTA-lanreotide: a novel tracer as a targeted agent for tumor therapy

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Sharmila; Das, Tapas; Chakraborty, Sudipta; Samuel, Grace; Korde, Aruna; Srivastava, Sudha; Venkatesh, Meera E-mail: meerav@apsara.barc.ernet.in; Pillai, M.R.A

    2004-08-01

    {sup 177}Lu of specific activity {approx}100-110 TBq/g and radionuclidic purity of {approx}100% was obtained by irradiation of enriched Lu{sub 2}O{sub 3} (60.6% {sup 176}Lu) target for 7 days at a thermal neutron flux of 3x10{sup 13}n/cm{sup 2}/sec. The {sup 177}Lu labeling of a macrocyclic bifunctional chelating agent viz. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has been extensively studied. Lanreotide, [{beta}-naphthyl-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH{sub 2}] a disulfide-linked cyclic octapeptide and a somatostatin analog, reported to bind with a wide variety of tumors expressing somatostatin receptors, was conjugated with DOTA. The peptide-BFCA conjugate was characterized with the help of high-resolution two-dimensional proton NMR spectroscopy. The {sup 177}Lu labeling of the DOTA-lanreotide conjugate has been standardized to give a radiolabeling yield of 85%. The tracer showed specific binding with A-431 human epidermoid carcinoma and IMR-32 human brain neuroblastoma cells.

  6. Subacute haematotoxicity after PRRT with {sup 177}Lu-DOTA-octreotate: prognostic factors, incidence and course

    Energy Technology Data Exchange (ETDEWEB)

    Bergsma, Hendrik; Konijnenberg, Mark W.; Kam, Boen L.R.; Teunissen, Jaap J.M.; Kooij, Peter P.; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus University Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, Wouter W. de [Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Franssen, Gaston J.H.; Eijck, Casper H.J. van [Erasmus Medical Center, Department of Surgery, Rotterdam (Netherlands)

    2016-03-15

    In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from {sup 131}I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with {sup 177}Lu-DOTA{sup 0}-Tyr{sup 3}-octreotate ({sup 177}Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit. The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined. Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0 x 10{sup 9}/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67 ± 7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq {sup 177}Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients. The incidence of subacute haematological toxicity after PRRT with {sup 177}Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from {sup 131}I, seems not to be valid for PRRT with {sup 177}Lu-DOTATATE. (orig.)

  7. Gamma camera calibration and validation for quantitative SPECT imaging with (177)Lu.

    Science.gov (United States)

    D'Arienzo, M; Cazzato, M; Cozzella, M L; Cox, M; D'Andrea, M; Fazio, A; Fenwick, A; Iaccarino, G; Johansson, L; Strigari, L; Ungania, S; De Felice, P

    2016-06-01

    Over the last years (177)Lu has received considerable attention from the clinical nuclear medicine community thanks to its wide range of applications in molecular radiotherapy, especially in peptide-receptor radionuclide therapy (PRRT). In addition to short-range beta particles, (177)Lu emits low energy gamma radiation of 113keV and 208keV that allows gamma camera quantitative imaging. Despite quantitative cancer imaging in molecular radiotherapy having been proven to be a key instrument for the assessment of therapeutic response, at present no general clinically accepted quantitative imaging protocol exists and absolute quantification studies are usually based on individual initiatives. The aim of this work was to develop and evaluate an approach to gamma camera calibration for absolute quantification in tomographic imaging with (177)Lu. We assessed the gamma camera calibration factors for a Philips IRIX and Philips AXIS gamma camera system using various reference geometries, both in air and in water. Images were corrected for the major effects that contribute to image degradation, i.e. attenuation, scatter and dead- time. We validated our method in non-reference geometry using an anthropomorphic torso phantom provided with the liver cavity uniformly filled with (177)LuCl3. Our results showed that calibration factors depend on the particular reference condition. In general, acquisitions performed with the IRIX gamma camera provided good results at 208keV, with agreement within 5% for all geometries. The use of a Jaszczak 16mL hollow sphere in water provided calibration factors capable of recovering the activity in anthropomorphic geometry within 1% for the 208keV peak, for both gamma cameras. The point source provided the poorest results, most likely because scatter and attenuation correction are not incorporated in the calibration factor. However, for both gamma cameras all geometries provided calibration factors capable of recovering the activity in

  8. [beta-Radiation exposure with (188)Re-labelled pharmaceuticals].

    Science.gov (United States)

    Andreeff, M; Wunderlich, G; Behge, K; Schönmuth, Th; Kotzerke, J

    2005-01-01

    The number of therapies with radiopharmaceuticals labelled with (188)Re is increasing requiring the documentation of the beta radiation exposure Hp(0.07) of the staff at all working and production sites and during the application and follow-up of the patient according to the new German Radiation Protection Law (StrlSchV). However, data for beta-radiation exposure are rare. Therefore, we determined the personal dose Hp(0.07) of the skin of the hands handling (188)Re radiopharmaceuticals to identify steps of high radiation exposure and to optimize working conditions. Thermoluminescence dosimeters (TLD 100) were fixed to the fingertips of the radiochemist, the physician and the nurse and compared to official ring dosimeters. In addition, to monitor radiation exposure continuously readable electronic beta- and gamma dosimeters EPD (Siemens) were used. At eight days in which therapies were performed these readings were evaluated. Considering one therapy with a (188)Re-labelled radiopharmaceutical the middle finger of the radiochemist (production) and the physician (application) showed a radiation burden of 894 and 664 muSv/GBq, respectively. The cumulative dose of the fingertips after eight days of therapy was 249 and 110 mSv for the radiochemist and physician, respectively. A cumulative finger dose after eight days of therapy of 17 and 38 muSv/GBq was found for physician and nurse leading to a Hp(0.07) of 3 and 6 mSv, respectively. Preparing the radiopharmaceutical labelled with 20GBq of (188)Re the reading of the personal electronic dosimeter of the radiochemist showed a gamma-dose rate Hp(10) of 55 muSv/h and a beta-dose rate Hp(0.07) of 663 muSv/h which are obviously not representative for the true radiation dose to the skin of the fingertips. During therapy with (188)Re-labelled radiopharmaceuticals the true radiation dose to the skin of the finger tips exceeds by far the readings of the official ring dosimeters as well as the continuously readable beta- and gamma

  9. DNA damage in blood lymphocytes in patients after {sup 177}Lu peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Eberlein, Uta; Bluemel, Christina; Buck, Andreas Konrad; Werner, Rudolf Alexander; Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nowak, Carina; Scherthan, Harry [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany)

    2015-10-15

    The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with {sup 177}Lu-labelled DOTATATE/DOTATOC. The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time-activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with {sup 131}I and {sup 177}Lu. The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair. Measurements of RIF and the absorbed dose to the blood after systemic administration of {sup 177}Lu may be used to obtain data on the individual dose-response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair. (orig.)

  10. {sup 177}Lu-DOTMP: a viable agent for palliative radiotherapy of painful bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Das, T.; Chakraborty, S.; Banerjee, S. [Radiopharmaceuticals Div., Bhabha Atomic Research Centre, Mumbai (India); Sarma, H.D. [Radiation Biology and Health Sciences Div., Bhabha Atomic Research Centre, Mumbai (India)

    2008-07-01

    The suitable nuclear decay characteristics [T{sub 1/2} = 6.73 d, E{sub {beta}}{sub (max)} = 497 keV, E{sub {gamma}} = 113 keV (6.4%), 208 keV (11%)] as well as the feasibility of large-scale production with adequate specific activity and radionuclidic purity using a moderate flux reactor are important attributes towards {sup 177}Lu to be considered as a promising radionuclide for palliative care in painful bone metastasis. The present study describes the preparation of {sup 177}Lu complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) and its preliminary biological evaluation in animal models with an aim to proposing it as a viable radiopharmaceutical for bone pain palliation. The choice DOTMP as the polyaminophosphonic acid carrier ligand is based on the enhanced thermodynamic stability and kinetic inertness of the metal-ligand complexes with macrocyclic chelators. {sup 177}Lu was produced with a specific activity of {proportional_to} 12 GBq/mg ({proportional_to} 324 mCi/mg) and radionuclidic purity of 99.98% by irradiation of natural Lu{sub 2}O{sub 3} target at a thermal neutron flux of {proportional_to} 6 x 10{sup 13} n/cm{sup 2} s for 21 d. {sup 177}Lu-DOTMP complex was prepared in high yield and excellent radiochemical purity (> 99%) using DOTMP synthesized and characterized in-house. The complex exhibited excellent in-vitro stability at room temperature. Biodistribution studies in Wistar rats showed rapid skeletal accumulation of the injected activity [(1.60{+-}0.19)% per gram in femur at 3 h post-injection] with fast clearance from blood and minimal uptake in any of the major organs. Scintigraphic studies carried out in normal Wistar rats and New Zealand white rabbits also demonstrated significant accumulation of the agent in skeleton and almost no retention in any other vital organs. (orig.)

  11. A study on indirect radiolabeling of IgG with carrier free 188Re

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    188Re labeled monoclonal antibodies are potential candidates for use in radioimmunotherapy. S-Bz-MAG3 as a bifunctional chelating agent was used for labeling of IgG with carrier free 188Re by pre-radiolabeling of the chelating approach. The conjugation conditions were optimized. The stability of 188Re-MAG3-IgG in vitro was high. The results may be useful to the studies of 188Re labeled MAbs for radioimmunotherapy.

  12. 177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice

    Science.gov (United States)

    Repetto-Llamazares, Ada H. V.; Larsen, Roy H.; Giusti, Anna Maria; Riccardi, Elena; Bruland, Øyvind S.; Selbo, Pål Kristian; Dahle, Jostein

    2014-01-01

    Background CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia cells (CLL). The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC) 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin). The present toxicity study was performed prior to initiation of clinical studieswith 177Lu-HH1. Methodology/Principal Findings Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group. Conclusions/Significance 177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients. PMID:25068508

  13. 177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL and chronic lymphocytic leukemia cells (CLL. The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin. The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group.177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

  14. Preparation and biological evaluation of {sup 177}Lu conjugated PR81 for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Salouti, Mojtaba, E-mail: saloutim@yahoo.com [Department of Biology, Faculty of Sciences, Zanjan Branch, Islamic Azad University, Zanjan 45156-58145 (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Biomolecule Laboratory, Radioisotope Department, Nuclear Science and Technology Research Institute, Tehran 14144-1339 (Iran, Islamic Republic of); Rajabi, Hossein [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of); Rasaee, Mohammad javad [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of)

    2011-08-15

    Aim: PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer. Materials and Methods: The radiochemical purity and in vitro stability of {sup 177}Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor. Results: The radiochemical purity was 91.2{+-}3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1{+-}3.4% and 76.2{+-}3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4{+-}2.4%. The cell toxicity study showed that the complex inhibited 85.2{+-}3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity. Conclusion: The results showed that one may consider {sup 177}Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations.

  15. Realistic multi-cellular dosimetry for (177)Lu-labelled antibodies: model and application.

    Science.gov (United States)

    Marcatili, S; Pichard, A; Courteau, A; Ladjohounlou, R; Navarro-Teulon, I; Repetto-Llamazares, A; Heyerdahl, H; Dahle, J; Pouget, J P; Bardiès, M

    2016-10-07

    Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin(®), a novel (177)Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of (177)Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

  16. Realistic multi-cellular dosimetry for 177Lu-labelled antibodies: model and application

    Science.gov (United States)

    Marcatili, S.; Pichard, A.; Courteau, A.; Ladjohounlou, R.; Navarro-Teulon, I.; Repetto-Llamazares, A.; Heyerdahl, H.; Dahle, J.; Pouget, J. P.; Bardiès, M.

    2016-10-01

    Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin®, a novel 177Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of 177Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

  17. Reducing Renal Uptake of {sup 177}Lu Labeled CCK Derivative using Basic Amino Acids

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soyoung; Lim, Jaecheong; Joh, Eunha [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    Radiolabeled peptides have been designed to target the relative receptors overespressed in tumor cells, such as integrin αvβ3, gastrin-releasing peptide receptor (GRPR), melanocortin-1 receptor (MC1-R), glucagon-like peptide-a receptor (GLP-1R), and cholecystokinin (CCK) receptor. Most of these peptides are eliminated from the body via the kidney and are partly reabsorbed in the proximal tubular cells. However, the high renal uptake of the radiolabeled peptides may lead to renal toxicity. In this study we investigated various amino acid solutions to reduce the renal uptake of {sup 177}Lu-DOTA-CCK derivative. Renal uptake of {sup 177}Lu-DOTA-CCK derivative is effectively reduced by the administration of positively charged amino acids. The administration of 12 mg of L-lysine was as effective in reducing the renal uptake as 6 mg of lysine and 6 mg of arginine combinations. Further studies will be performed to identify the most potent inhibitor of renal reuptake of radiolabeled peptides and minimize the chance of unwanted side effects.

  18. Evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapy agent targeting VEGF expressing cancers.

    Science.gov (United States)

    Kameswaran, Mythili; Pandey, Usha; Gamre, Naresh; Vimalnath, K V; Sarma, Haladhar Dev; Dash, Ashutosh

    2016-08-01

    This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0±0.6%. In vitro stability was retained upto 4 days at 37°C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of {sup 177}Lu-EDTMP, a potential bone pain palliation agent

    Energy Technology Data Exchange (ETDEWEB)

    Mathe, Domokos [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)], E-mail: mdomokos@hp.osski.hu; Balogh, Lajos; Polyak, Andras; Kiraly, Reka [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary); Marian, Terez [Institute of Nuclear Medicine, Debrecen University, Debrecen (Hungary); Pawlak, Dariusz [Institute of Atomic Energy, Radioisotope Centre POLATOM, Swierk-Otwock (Poland); Zaknun, John J.; Pillai, Maroor R.A. [International Atomic Energy Agency (IAEA), Vienna (Austria); Janoki, Gyozo A. [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)

    2010-02-15

    Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low {beta}- energy, {sup 177}Lu [T{sub 1/2}=6.73 days, E{sub {beta}}{sub max}=497 keV, E{sub {gamma}}=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of {sup 177}Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: {sup 177}Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of {sup 177}Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: {sup 177}Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of {sup 177}Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing {sup 177}Lu does not alter its biological behaviour as a specific bone

  20. Hypocalcaemia after treatment with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Vliet, Esther I. van; Kam, Boen L.R.; Teunissen, Jaap J.M.; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus MC, University Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Zillikens, M.C.; Peeters, Robin P. [Erasmus MC, University Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Rijke, Yolanda B. de [Erasmus MC, University Medical Center, Department of Clinical Chemistry, Rotterdam (Netherlands)

    2013-12-15

    The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D{sub 3}, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 {+-} 0.01 to 2.26 {+-} 0.02 mmol/l, p = 0.02). Eight patients (17 %) showed a marked decrease in serum calcium levels with a nadir of {<=}2.10 mmol/l. In five patients (11 %), calcium substitution therapy was prescribed. PTH increased significantly (5.9 {+-} 0.6 to 6.7 {+-} 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 {+-} 3 to 77 {+-} 3 {mu}mol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 {+-} 0.01 at baseline to a nadir of 2.24 {+-} 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22 %) showed a serum calcium nadir of {<=}2.10 mmol/l, and 11

  1. Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity.C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys. At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a global transcriptional variations in kidney tissues, (b morphological changes in the kidneys, (c changes in white and red blood cell count as well as blood levels of urea, and (d changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy.In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months.Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm applicability of these

  2. A systematic study on the utility of CHX-A''-DTPA-NCS and NOTA-NCS as bifunctional chelators for (177)Lu radiopharmaceuticals.

    Science.gov (United States)

    Pandey, Usha; Gamre, Naresh; Lohar, Sharad Pandurang; Dash, Ashutosh

    2017-09-01

    This paper describes the evaluation of [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA-NCS) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) as bifunctional chelators for (177)Lu. While (177)Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of (177)Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of (177)Lu-NOTA-NCS significantly as compared to (177)Lu-CHX-A''-DTPA-NCS. In vitro stability of (177)Lu-CHX-A''-DTPA-NCS was also superior to (177)Lu-NOTA-NCS. It could be concluded from this study that among the two chelators evaluated, CHX-A''-DTPA-NCS is more appropriate for preparation of (177)Lu radiopharmaceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Improving quantitative dosimetry in (177)Lu-DOTATATE SPECT by energy window-based scatter corrections

    DEFF Research Database (Denmark)

    de Nijs, Robin; Lagerburg, Vera; Klausen, Thomas L

    2014-01-01

    and the activity, which depends on the collimator type, the utilized energy windows and the applied scatter correction techniques. In this study, energy window subtraction-based scatter correction methods are compared experimentally and quantitatively. MATERIALS AND METHODS: (177)Lu SPECT images of a phantom...... with known activity concentration ratio between the uniform background and filled hollow spheres were acquired for three different collimators: low-energy high resolution (LEHR), low-energy general purpose (LEGP) and medium-energy general purpose (MEGP). Counts were collected in several energy windows......, and scatter correction was performed by applying different methods such as effective scatter source estimation (ESSE), triple-energy and dual-energy window, double-photopeak window and downscatter correction. The intensity ratio between the spheres and the background was measured and corrected for the partial...

  4. Effect of amplified spontaneous emission on selectivity of laser photoionisation of the 177Lu radioisotope

    Science.gov (United States)

    D'yachkov, A. B.; Gorkunov, A. A.; Labozin, A. V.; Mironov, S. M.; Panchenko, V. Ya; Firsov, V. A.; Tsvetkov, G. O.

    2016-06-01

    A significant deselecting effect of amplified spontaneous emission has been observed in the experiments on selective laser photoionisation of the 177Lu radioisotope according to the scheme 5d6s2 2D3/2 → 5d6s6p 4Fo5/2 (18505 cm-1) → 5d6s7s 4D3/2(37194 cm-1) → autoionisation state (53375 cm-1). The effect is conditioned by involvement of non-target isotopes from the lower metastable level 5d6s2 2D5/2(1994 cm-1) into the ionisation process. Spectral filtering of spontaneous emission has allowed us to significantly increase the selectivity of the photoionisation process of the radioisotope and to attain a selectivity value of 105 when using saturating light intensities.

  5. Photon strength functions in 177Lu: Study of scissors resonance in high-spin region

    Directory of Open Access Journals (Sweden)

    Bečvář F.

    2015-01-01

    Full Text Available The nucleus 177Lu is characteristic by an unusually high value of the thermal-neutron capturing state spin, J = 13/2, and by distinct low-energy rotational bands built on the 7/2+ ground state and the 9/2− level at 150 keV. The γ cascades connecting the capturing state with the members of these bands carry unique information about the role of identical M1 scissors-mode resonances, built according to Brink hypothesis assumingly on each energy level, even in conditions of fast nuclear rotation. With this motivation we measured a set of spectra of two-step γ cascades following the thermal neutron capture in 176Lu. The measurement was performed at neutron beam of the LWR-15 Reactor in Řež. From the analysis of these spectra the common parameters of the scissors resonances were deduced. The obtained results are discussed.

  6. Anti-EGFRvIII monoclonal antibody armed with {sup 177}Lu: in vivo comparison of macrocyclic and acyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hens, Marc; Vaidyanathan, Ganesan; Zhao Xiaoguang [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R., E-mail: zalut001@mc.duke.ed [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)

    2010-10-15

    Introduction: Monoclonal antibody (mAb) L8A4 binds specifically to the epidermal growth factor receptor variant III (EGFRvIII) that is present on gliomas but not on normal tissues, and is internalized rapidly after receptor binding. Because of the short range of its {beta}-emissions, labeling this mAb with {sup 177}Lu would be an attractive approach for the treatment of residual tumor margins remaining after surgical debulking of brain tumors. Materials and Methods: L8A4 mAb was labeled with {sup 177}Lu using the acyclic ligands [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1, 2-diamine-pentaacetic acid (CHX-A''-DTPA) and 2-(4-isothiocyanatobenzyl)-6-methyldiethylene-triaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and {alpha}-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (MeO-DOTA). Paired-label tissue distribution experiments were performed in athymic mice bearing subcutaneous EGFRvIII-expressing U87.{Delta}EGFR glioma xenografts over a period of 1 to 8 days to directly compare {sup 177}Lu-labeled L8A4 to L8A4 labeled with {sup 125}I using N-succinimidyl 4-guanidinomethyl-3-[{sup 125}I]iodobenzoate ([{sup 125}I]SGMIB). Results: Except with C-DOTA, tumor uptake for the {sup 177}Lu-labeled mAb was significantly higher than the co-administered radioiodinated preparation; however, this was also the case for spleen, liver, bone and kidneys. Tumor/normal tissue ratios for {sup 177}Lu-1B4M-DTPA-L8A4 and, to an even greater extent, {sup 177}Lu-MeO-DOTA-L8A4 were higher than those for [{sup 125}I]SGMIB-L8A4 in most other tissues. Conclusions: Tumor and normal tissue distribution patterns for this anti-EGFRvIII mAb were dependent on the nature of the bifunctional chelate used for {sup 177}Lu labeling. Optimal results were obtained with 1B4M-DTPA and MeO-DOTA, suggesting no clear advantage

  7. Preparation and bioevaluation of {sup 177}Lu-labelled anti-CD44 for radioimmunotherapy of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Young; Hong, Young Don; Jung, Sung Hee; Choi, Sun Ju [Radioisotope Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-12-15

    CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the {sup 177}Lu-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based dtPA-ncS and radioimmunoconjugated with {sup 177}Lu at room temperature within 15 minutes. the stability was tested in human serum. An in vitro study was carried out in Ht-29 human colon cancer cell lines. For the biodistribution study {sup 177}Lu-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteinebased dtPA-ncS and purified by a centricon filter system having a molecular cut-off of 50 kda. radioimmunoconjugation with {sup 177}Lu was reacted for 15 min at room temperature. the radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. the anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with {sup 177}Lu. the in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. this radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

  8. Preparation and Biological Evaluation of 188Re Labeled Monoclonal Antibody TGLA

    Institute of Scientific and Technical Information of China (English)

    WEN; Kai; ZHANG; Jun-li; CHEN; Bao-jun; CUI; Hai-ping

    2012-01-01

    <正>Monoclonal antibody TGLA is a specific targeting CD20 chimeric antibody. It can kill tumor cells and inhibit tumor cells’ growth effectively, which has been applied to clinical therapy of lymphoma cell B. 188 Re is easy to get, and emits both β and γ rays. 188Re labeled monoclonal antibody TGLA can be used for the study of lymphoma therapy and imaging. This work got the product 188Re-TGLA by direct labeling

  9. Development of [{sup 90}Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan)], E-mail: kogawa@med.kanazawa-u.ac.jp; Kawashima, Hidekazu [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Shiba, Kazuhiro [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Washiyama, Kohshin; Yoshimoto, Mitsuyoshi [Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0942 (Japan); Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun 910-1193 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Ueda, Masashi [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Mori, Hirofumi [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Saji, Hideo [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2009-02-15

    Introduction: Based on the concept of bifunctional radiopharmaceuticals, we have previously developed {sup 186}Re-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed {sup 90}Y-labeled radiopharmaceutical could be developed. Methods: In this study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [{sup 90}Y]DOTA-complex-conjugated bisphosphonate ([{sup 90}Y]DOTA-HBP) was prepared by coordination with {sup 90}Y, and its biodistribution was studied in comparison to [{sup 90}Y]citrate. Results: In biodistribution experiments, [{sup 90}Y]DOTA-HBP and [{sup 90}Y]citrate rapidly accumulated and resided in the bone. Although [{sup 90}Y]citrate showed a higher level of accumulation in the bone than [{sup 90}Y]DOTA-HBP, the clearances of [{sup 90}Y]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [{sup 90}Y]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [{sup 90}Y]DOTA-HBP were lower than those of [{sup 90}Y]citrate. Conclusions: [{sup 90}Y]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [{sup 90}Y]citrate. Since the DOTA ligand forms a stable complex not only with {sup 90}Y but also with lutetium ({sup 177}Lu), indium ({sup 111}In), gallium ({sup 67/68}Ga), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging.

  10. Preparation and primary biological evaluation of novel nitrido-188Re complexes/lipiodol

    Institute of Scientific and Technical Information of China (English)

    WANG Guanquan; WEI Hongyuan; LUO Shunzhong; HE Jiaheng; YANG Yuqing; WANG Wenjin; XIONG Xiaoling

    2008-01-01

    Two new nitrido-188Re complexes were prepared by a modified method in high yield.These complexes were stable in vitro.The biodistribution in normal mice showed that these nitrido-188Re complexes could accumulate in liver and dissipate quickly from almost all organs.TAE was performed with the use of lipiodol solutions of two complexes to rabbit VX2 liver tumor models.SPECT images showed that the two lipiodol solutions could remain in tumor for about 9 h (188ReN-NEPTDD/lipiodol) and 12 h (188ReN-NEMMPTDD/Iipiodol),respectively.

  11. Preparation and bio-distribution of bone tumor therapeutic agent 188Re-TCTMP

    Institute of Scientific and Technical Information of China (English)

    JIANG Shu-Bin; LUO Shun-Zhong; DENG Hou-Fu; BIN Wen-Zeng; WANG Wen-Jin; WEI Hong-Yuan; LIU Guo-Ping

    2004-01-01

    TCTMP ( 1,4,8,11-tetraaza cyclotetradecyl- 1,4,8,11-tetramethylene phosphonate) was synthesized and coupled with 188Re. The 188Re-TCTMP's coupling condition, stability and bio-distribution in mice were investigated.The results showed that satisfactory yield of 188Re could be obtained under the conditions of media pH=2.0, 0.8~1.6 mg of SnCl2 and 50 mg of ligand. 188Re-TCTMP was stable (complexation yield >95%) in 8 d without protection of N2. The result of bio-distribution indicated that 188Re-TCTMP had a strong affinity to skeleton and very low non-target tissue's uptake, and the amount of 188Re-TCTMP in blood was (0.06±0.02)%ID/g 6 h after injection,whereas the concentration of 188Re-HEDP (1-hydroxy-ethylidene diphosphonate) in blood was (0.28±0.05)%ID/g 6 hafter injection. Compared with 188Re-HEDP, 188Re-TCTMP exhibits better potential for the treatment of metastases.

  12. Levels of 188Re nucleus populated in thermal neutron capture reaction

    Science.gov (United States)

    Běrziņš, J.; Krasta, T.; Simonova, L.; Balodis, M.; Bondarenko, V.; Jentschel, M.; Urban, W.; Tomandl, I.

    2016-03-01

    Levels of 188Re populated in thermal neutron capture reaction with enriched 187Re targets have been studied. Single γ-ray spectrum of 188Re, measured with the high-resolution crystal diffraction spectrometer GAMS5, as well as γγ-coincidence experiments performed with high efficiency Ge detectors, allowed to develop model-independent level scheme of the doubly-odd 188Re nucleus up to ˜ 1.5 MeV excitation energy. Analysis of the established 188Re level scheme in terms of the quasiparticle-plus-rotor model indicates coexistence of axially-deformed and triaxial structures in the energy range above 400 keV.

  13. Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Keizer, Bart de; Kam, Boen L.R.; Essen, Martijn van; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam, P.O. Box 2040 (Netherlands); Aken, Maarten O. van; Feelders, Richard A.; Herder, Wouter W. de [Erasmus Medical Center, Section of Endocrinology, Department of Internal Medicine, Rotterdam (Netherlands)

    2008-04-15

    Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate). All {sup 177}Lu-octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included for analysis. Four hundred seventy-nine patients received a total of 1,693 administrations of {sup 177}Lu-octreotate. Six of 479 patients (1%) developed severe symptoms because of massive release of bioactive substances after the first cycle of {sup 177}Lu-octreotate. One patient had a metastatic hormone-producing small intestinal carcinoid; two patients had metastatic, hormone-producing bronchial carcinoids; two patients had vasoactive intestinal polypeptide-producing pancreatic endocrine tumors (VIPomas); and one patient had a metastatic pheochromocytoma. With adequate treatment, all patients eventually recovered. Hormonal crises after {sup 177}Lu-octreotate therapy occur in 1% of patients. Generally, {sup 177}Lu-octreotate therapy is well tolerated. (orig.)

  14. Exploitation of nano alumina for the chromatographic separation of clinical grade 188Re from 188W: a renaissance of the 188W/188Re generator technology.

    Science.gov (United States)

    Chakravarty, Rubel; Shukla, Rakesh; Ram, Ramu; Venkatesh, Meera; Tyagi, Avesh Kumar; Dash, Ashutosh

    2011-08-15

    The (188)W/(188)Re generator using an acidic alumina column for chromatographic separation of (188)Re has remained the most popular procedure world over. The capacity of bulk alumina for taking up tungstate ions is limited (∼50 mg W/g) necessitating the use of very high specific activity (188)W (185-370 GBq/g), which can be produced only in very few high flux reactors available in the world. In this context, the use of high-capacity sorbents would not only mitigate the requirement of high specific activity (188)W but also facilitate easy access to (188)Re. A solid state mechanochemical approach to synthesize nanocrystalline γ-Al(2)O(3) possessing very high W-sorption capacity (500 mg W/g) was developed. The structural and other investigations of the material were carried out using X-ray diffraction (XRD), transmission electron microscopy (TEM), Brunauer Emmett Teller (BET) surface area analysis, thermogravimetric-differential thermal analysis (TG-DTA), and dynamic light scattering (DLS) techniques. The synthesized material had an average crystallite size of ∼5 nm and surface area of 252 ± 10 m(2)/g. Sorption characteristics such as distribution ratios (K(d)), capacity, breakthrough profile, and elution behavior were investigated to ensure quantitative uptake of (188)W and selective elution of (188)Re. A 11.1 GBq (300 mCi) (188)W/(188)Re generator was developed using nanocrystalline γ-Al(2)O(3), and its performance was evaluated for a period of 6 months. The overall yield of (188)Re was >80%, with >99.999% radionuclidic purity and >99% radiochemical purity. The eluted (188)Re possessed appreciably high radioactive concentration and was compatible for the preparation of (188)Re labeled radiopharmaceuticals.

  15. Tumoral fibrosis effect on the radiation absorbed dose of {sup 177}Lu-Tyr{sup 3}-octreotate-gold nanoparticles and {sup 177}Lu-Tyr{sup 3}-octreotate radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Zambrano R, O. D.

    2015-07-01

    In this work was comparatively evaluated the effect of tumoral fibrosis in the radiation absorbed dose of the radiopharmaceutical {sup 177}Lu-Tyr{sup 3}-octreotate with and without gold nanoparticles. For this, was used an experimental array of tumoral fibrosis and computer models based on Monte Carlo calculations to simulate tumoral micro environments without fibrosis and with fibrosis. The computer simulation code Penelope (Penetration Energy Loss of Positron and Electrons) and MCNP (Monte Carlo N-particle Transport Code System) which are based on the Monte Carlo methodology were used to create the computer models for the simulation of the transport of particles (emitted by {sup 177}Lu) in the micro environments (without fibrosis and with fibrosis) with the purpose of calculating the radiation absorbed dose in the interstitial space and in the nucleus of cancer cells. The first computational model consisted of multiple concentric spheres (as onion shells) with the radioactive source homogeneously distributed in the shell between 5 and 10 μm in diameter which represents the internalization of the radioactive source into the cell cytoplasm as it occurs in target specific radiotherapy. The concentric spheres were useful to calculate the radiation absorbed dose in depth in the models without fibrosis and with fibrosis. Furthermore, there were constructed other computer models using two different codes that simulate the transport of radiation (Penelope and MCNP). These models consist of seven spheres that represent cancer cells (HeLa cells) of 10 μm in diameter and each one of them contain another smaller sphere in the center that represents the cell nucleus. A comparison was done of the radiation absorbed dose in the nucleus of the cells, calculated with both codes, Penelope and MCNP. The radioactive source ({sup 177}Lu) used for the simulations was given to the codes by means of a convoluted spectrum of the most important beta particles (high percentage emission

  16. Formulation of an inhibitor radiopharmaceutical of prostatic antigen of {sup 177}Lu-Glu-Nh-CO-Nh-Lys membrane; Formulacion de un radiofarmaco inhibidor del antigeno prostatico de membrana {sup 177}Lu-Glu-NH-CO-NH-Lys

    Energy Technology Data Exchange (ETDEWEB)

    Ortega S, D.

    2015-07-01

    The prostate specific membrane antigen (PSMA) is a zinc metalloenzyme that is expressed on the cell membrane and highly expressed in prostate cancer. Recently, it has been demonstrated that the peptide sequence Glu-Nh-CO-Nh-Lys inhibit PSMA activity through an electrostatic interaction with the Zn. Several theragnostic radiopharmaceuticals with base in {sup 177}Lu have been developed for radiotherapy of specific molecular targets because gamma and beta emissions of the radionuclide (β = 0.498 MeV and γ= 0.133 MeV). However, there is currently no label a formulation for preparing a radiopharmaceutical of {sup 177}Lu-Glu-Nh-CO-Nh-Lys useful treatment of prostate cancer. The aim of this research was to optimize and document the process of production of the radiopharmaceutical {sup 177}Lu-Glu-Nh-CO-Nh-Lys for sanitary registration application before the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). The optimization of the production process was assessed a factorial design of three variables with mixed levels (3 x 3 x 2) where the dependent variable is the radiochemical purity, the analytical method was validated by UV-Vis spectrophotometry. Next, process validation was carried out by labeling 3 lots of the optimized formulation of the radiopharmaceutical (5.55 GBq (2.16 μg) of {sup 177}LuCl{sub 3}, 90 mg peptide PSMA, 50 mg ascorbic acid and 150 μL of acetate buffer 1 M ph 5), long-term stability was performed by high resolution liquid chromatography) to determine its useful shelf life. 3 validation batches were prepared under protocols of Good Manufacturing Practice (GMP) in the Production Plant of Radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ), meet specifications preset by obtaining a sterile and free development of bacterial endotoxin yields of labeled 100% and which retains its quality characteristics radiochemical purity greater than 90% for at least 15 days. (Author)

  17. 177Lu-DTPA-BIS-BIOTIN的制备及正常鼠体内生物分布%Preparation of 177Lu-DTPA-BIS-BIOTIN and Biodistribution Evaluation in Normal Mice

    Institute of Scientific and Technical Information of China (English)

    邓新荣; 杜进; 罗志福

    2010-01-01

    研究了DTPA-BIS-BIOTIN的177Lu标记方法,优化了标记条件,并进行了标记物在正常小鼠体内分布实验.在最佳标记条件下(DTPA-BIS-BIOTIN 25 μg,标记介质pH=4.5,80℃反应20 min),177Lu-DTPA-BIS-BIOTIN标记率大于99.0%,室温下放置96 h,标记物体外稳定性良好.正常小鼠体内分布实验结果表明,177Lu-DTPA-BIS-BIOTIN在血液中清除快,主要浓集于肝、脾和肾,经肾脏排泄.本研究为进一步采用177Lu-DTPA-BIS-BIOTIN进行肿瘤预定位显像及治疗研究提供了实验基础.

  18. Therapeutic Efficacy with Treatment-related Toxicities of {sup 177}Lu-labeled Bombesin Derivative for the Peptide Receptor Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Cheong; Cho, Eun Ha; Lee, So Young [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    The gastrin-releasing peptide receptor (GRPR) has been shown to be overexpressed in many human tumours, including breast cancer, prostate cancer, small cell lung cancer, ovarian cancers, endometrial cancers, and gastrointestinal stromal tumors. In particular, GRPR expression is high in 83 % of invasive primary prostatic carcinomas. These results suggest that {sup 177}Lu-labeled bombesin derivative has promising characteristics as a novel nuclear medicine, especially for the treatment of GRPR over-expressing prostate tumors.

  19. 177Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical

    Directory of Open Access Journals (Sweden)

    Héctor Mendoza-Nava

    2016-01-01

    Full Text Available 177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4-folate-bombesin with gold nanoparticles (AuNPs in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs and gastrin-releasing peptide receptors (GRPRs overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys1Lys3(DOTA-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS, particle size distribution (DLS, TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%. Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15±2.72%. 177Lu-dendrimer(AuNP-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.

  20. Long-term toxicity of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Bijster, Magda; Jong, Marion de [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Visser, Theo J. [Erasmus MC Rotterdam, Department of Internal Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC Rotterdam, Department of Pathology, Rotterdam (Netherlands); Lindemans, Jan [Erasmus MC Rotterdam, Department of Clinical Chemistry, Rotterdam (Netherlands)

    2007-02-15

    Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney, which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models. Significant renal toxicity was detected beyond 100 days after start of treatment as shown by elevated serum creatinine and proteinuria. Microscopically, tubules were strongly dilated with flat epithelium, containing protein cylinders. Creatinine levels rose significantly after 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, but were significantly lower after 278 MBq (single injection) or two weekly doses of 278 MBq. Renal damage scores were maximal after 555 MBq and significantly lower in the 278 and 2 x 278 MBq groups. Three doses of 185 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469{+-}18, 134{+-}70 and 65{+-}15 {mu}mol/l, respectively; p<0.001). Renal histological damage scores were not significantly influenced by dose fractionation. Lysine co-administration with three weekly treatments of 185 MBq significantly lowered serum creatinine and proteinuria. Injection of high doses of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage. (orig.)

  1. Distinct microRNA expression profiles in mouse renal cortical tissue after 177Lu-octreotate administration.

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available The aim of this study was to investigate the variation of the miRNA expression levels in normal renal cortical tissue after 177Lu-octreotate administration, a radiopharmaceutical used for treatment of neuroendocrine cancers.Female BALB/c nude mice were i.v. injected with 1.3, 3.6, 14, 45, or 140 MBq 177Lu-octreotate, while control animals received saline. The animals were killed at 24 h after injection and total RNA, including miRNA, was extracted from the renal cortical tissue and hybridized to the Mouse miRNA Oligo chip 4plex to identify differentially regulated miRNAs between exposed and control samples.In total, 57 specific miRNAs were differentially regulated in the exposed renal cortical tissues with 1, 29, 21, 27, and 31 miRNAs identified per dose-level (0.13, 0.34, 1.3, 4.3, and 13 Gy, respectively. No miRNAs were commonly regulated at all dose levels. miR-194, miR-107, miR-3090, and miR-3077 were commonly regulated at 0.34, 1.3, 4.3, and 13 Gy. Strong effects on cellular mechanisms ranging from immune response to p53 signaling and cancer-related pathways were observed at the highest absorbed dose. Thirty-nine of the 57 differentially regulated miRNAs identified in the present study have previously been associated with response to ionizing radiation, indicating common radiation responsive pathways.In conclusion, the 177Lu-octreotate associated miRNA signatures were generally dose-specific, thereby illustrating transcriptional regulation of radiation responsive miRNAs. Taken together, these results imply the importance of miRNAs in early immunological responses in the kidneys following 177Lu-octreotate administration.

  2. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez C, J.; Murphy, C.A. de; Pedraza L, M. [Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, 14000 Mexico D.F. (Mexico); Ferro F, G. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, 06000 Mexico D.F. (Mexico)

    2006-07-01

    Malignant pancreas tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses after administration of {sup 177}Lu-DOTA-TATE in mice as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (n=18) to obtain the {sup 177}Lu-DOTA-TATE biokinetics and dosimetry. To estimate its therapeutic efficacy 87 MBq were injected in a tail vein of 3 mice and 19 days p.i. there were a partial relapse. There was an epithelial and sarcoma mixed tumour in the kidneys of mouse III. The absorbed dose to tumour, kidney and pancreas was 50.5 {+-} 7.2 Gy, 17.5 {+-} 2.5 Gy and 12.6 {+-} 2.3 Gy respectively. These studies justify further therapeutic and dosimetry estimations to ensure that {sup 177}Lu-DOTA-TATE will act as expected in man considering its kidney radiotoxicity. (Author)

  3. {sup 177}Lu-immunotherapy of experimental peritoneal carcinomatosis shows comparable effectiveness to {sup 213}Bi-immunotherapy, but causes toxicity not observed with {sup 213}Bi

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, Christof; Zoeckler, Christine; Beck, Roswitha; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Quintanilla-Martinez, Leticia [Universitaetsklinikum Tuebingen, Institute for Pathology, Tuebingen (Germany); Bruchertseifer, Frank [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2011-02-15

    {sup 213}Bi-d9MAb-immunoconjugates targeting gastric cancer cells have effectively cured peritoneal carcinomatosis in a nude mouse model following intraperitoneal injection. Because the {beta}-emitter {sup 177}Lu has proven to be beneficial in targeted therapy, {sup 177}Lu-d9MAb was investigated in this study in order to compare its therapeutic efficacy and toxicity with those of {sup 213}Bi-d9MAb. Nude mice were inoculated intraperitoneally with HSC45-M2 gastric cancer cells expressing d9-E-cadherin and were treated intraperitoneally 1 or 8 days later with different activities of specific {sup 177}Lu-d9MAb immunoconjugates targeting d9-E-cadherin or with nonspecific {sup 177}Lu-d8MAb. Therapeutic efficacy was evaluated by monitoring survival for up to 250 days. For evaluation of toxicity, both biodistribution of {sup 177}Lu-d9MAb and blood cell counts were determined at different time points and organs were examined histopathologically. Treatment with {sup 177}Lu-immunoconjugates (1.85, 7.4, 14.8 MBq) significantly prolonged survival. As expected, treatment on day 1 after tumour cell inoculation was more effective than treatment on day 8, and specific {sup 177}Lu-d9MAb conjugates were superior to nonspecific {sup 177}Lu-d8MAb. Treatment with 7.4 MBq of {sup 177}Lu-d9MAb was most successful, with 90% of the animals surviving longer than 250 days. However, treatment with therapeutically effective activities of {sup 177}Lu-d9MAb was not free of toxic side effects. In some animals lymphoblastic lymphoma, proliferative glomerulonephritis and hepatocarcinoma were seen but were not observed after treatment with {sup 213}Bi-d9MAb at comparable therapeutic efficacy. The therapeutic efficacy of {sup 177}Lu-d9MAb conjugates in peritoneal carcinomatosis is impaired by toxic side effects. Because previous therapy with {sup 213}Bi-d9MAb revealed comparable therapeutic efficacy without toxicity it should be preferred for the treatment of peritoneal carcinomatosis. (orig.)

  4. {sup 177}Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India

    Energy Technology Data Exchange (ETDEWEB)

    Danthala, Madhav; Raghavendra Rao, M. [HCG Oncology Hospitals, Bangalore, Karnataka (India); Kallur, K.G.; Prashant, G.R.; Rajkumar, K. [HCG Oncology Hospitals, Department of Nuclear Medicine, Bangalore, Karnataka (India)

    2014-07-15

    The choice of an appropriate treatment option in patients with inoperable or metastatic neuroendocrine tumours (NETs) is limited, and approximately 50 % of patients have advanced NET at diagnosis, and 65 % die within 5 years. Treatment with {sup 177}Lu-DOTATATE ({sup 177}Lu-[DOTA{sup 0},Tyr{sup 3}] octreotate) is a promising new option in the treatment of metastatic NETs. Patients with metastatic NET who underwent {sup 177}Lu-DOTATATE during the period 2009 to 2013 were included in this retrospective study. Follow-up imaging studies including a {sup 68}Ga-DOTANOC PET/CT scan and a posttherapy {sup 177}Lu-DOTATATE scan were compared with baseline imaging to determine response to treatment. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and Cox regression analysis was also done. Ten patients (25 %) had a minimal response, 13 (32.5 %) had a partial response and 9 (22.5 %) had stable disease. Progressive disease was seen in 8 patients (20 %), including 6 patients who died during or after the treatment period. The estimated mean PFS in those who received one or two cycles of {sup 177}Lu-DOTATATE was 8.3 months (95 % CI 6.2 to 10.3 months) compared to an estimated mean PFS of 45.6 months (95 % CI 40.9 to 50.2 months) in those who received more than two cycles of {sup 177}Lu-DOTATATE (log-rank Mantel-Cox Χ {sup 2} = 8.01, p = 0.005). Our study showed that treatment with {sup 177}Lu-DOTATATE should be considered in the management of NETs, considering the limited success of alternative treatment modalities. Treatment response and PFS is determined primarily by the dose delivered and best results are obtained when more than two cycles of {sup 177}Lu-DOTATATE are given, with careful monitoring for possible side effects. (orig.)

  5. Dosimetry for {sup 177}Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Delker, Andreas; Fendler, Wolfgang Peter; Brunegraf, Anika; Gosewisch, Astrid; Gildehaus, Franz Josef; Bartenstein, Peter; Boening, Guido [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Kratochwil, Clemens; Haberkorn, Uwe [Heidelberg University Hospital, Department for Nuclear Medicine, Heidelberg (Germany); Tritschler, Stefan; Stief, Christian Georg [Ludwig-Maximilians-University of Munich, Department of Urology, Munich (Germany); Kopka, Klaus [German Cancer Research Center (dkfz), Division of Radiopharmaceutical Chemistry, Heidelberg (Germany)

    2016-01-15

    Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand {sup 177}Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) {sup 177}Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with {sup 177}Lu-DKFZ-PSMA-617. We suggest that {sup 177}Lu-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour

  6. The challenges of treating paraganglioma patients with {sup 177}Lu-DOTATATE PRRT: Catecholamine crises, tumor lysis syndrome and the need for modification of treatment protocols

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William; Mccann, Karey; Mcewan, Alexander J. B. [Dept. of Diagnostic Imaging, Cross Cancer Institute, Alberta (China)

    2015-09-15

    A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted radioisotope therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with {sup 177}Lu-[DOTA0,Tyr3]octreotate (DOTATATE) radioisotope therapy using established protocols. Three paraganglioma patients were treated with 4–5 cycles of {sup 177}Lu-DOTATATE and were evaluated for side effects and response to therapy. Two of the three patients developed severe adverse reactions following their first {sup 177}Lu-DOTATATE treatment. One patient developed a catecholamine crisis and tumor lysis syndrome within hours of treatment, requiring intensive care unit (ICU) support, and another developed a catecholamine crisis 3 days after treatment, requiring hospitalization. The treatment protocols at our institution were subsequently modified by increasing the radioisotope infusion time from 15 to 30 min, as recommended in the literature, to 2–4 h and by reducing the administered dose of {sup 177}Lu-DOTATATE. Subsequent {sup 177}Lu-DOTATATE treatments utilizing the modified protocols were well tolerated, and response to therapy was achieved in all three patients, resulting in significantly improved quality of life. {sup 177}Lu-DOTATATE is an exciting new therapeutic option in the management of paragangliomas; however, current treatment protocols described in the literature may need to be modified by lengthening the infusion time and/or lowering the initial treatment dose to prevent or reduce the severity of adverse reactions.

  7. Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs in vivo

    Directory of Open Access Journals (Sweden)

    Tang QS

    2011-11-01

    Full Text Available Qiu-Sha Tang1,*, Dao-Zhen Chen2,*, Wen-Qun Xue2, Jing-Ying Xiang2, Yong-Chi Gong1, Li Zhang2, Cai-Qin Guo21Department of Pathology and Pathophysiology, Medical College, Southeast University, Nanjing, Jiangsu; 2Central Laboratory, Wuxi Hospital for Maternal and Child Health Care, Affiliated Medical School of Nanjin, Wuxi, Jiangsu, China *Authors contributed equally to this workBackground: The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide 188Re-labeled folic acid ligand (188Re-folate-CDDP/HSA.Methods: Human serum albumin was labeled with 188Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g was measured in vital organs. The biodistribution of 188Re-folate-CDDP/HAS magnetic nanoparticles was assessed.Results: Optimal conditions for 188Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L, 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL, 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L, 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and 188ReO4 eluent (0.1 mL. The rate of 188Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the 188Re-folate-CDDP/HSA magnetic nanoparticles

  8. Rhenium-188: Availability from the W-188/Re-188 Generator and Status of Current Applications

    Energy Technology Data Exchange (ETDEWEB)

    Pillai, M R A [Bhabha Atomic Research Centre, Mumbai, India; Dash, A [Bhabha Atomic Research Centre, Mumbai, India; Knapp Jr, Russ F [ORNL

    2012-01-01

    Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting - particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 KeV, 15.1%). The 188W/188Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) 188Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent 188W radionuclide have been a major impediment in the progress of application of 188Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade 188W/188Re generator. Since the specific activity of 188W used in the generator is relatively low (<5 Ci/g), the eluted 188ReO4- can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful 188ReO4-. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on 188Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability, and use of188Re including a discussion of why broader use of 188Re has not progressed as ecpected as a popular radionuclide for therapy.

  9. Evaluation of the therapeutic efficacy and radiotoxicity of the conjugates {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} and {sup 177}Lu-DOTA-GGC-AuNP-c[RGDfk(C)] in a murine model and their relationship with the inhibition of the angiogenic factors VEGF and HIF-1α; Evaluacion de la eficacia terapeutica y radiotoxicidad de los conjugados {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} y {sup 177}Lu-DOTA-GGC-AuNP-c[RGDfK(C)] en un modelo murino y su relacion con la inhibicion de los factores angiogenicos VEGF y HIF-1α

    Energy Technology Data Exchange (ETDEWEB)

    Vilchis J, A.

    2013-07-01

    Molecular targeting therapy has become a relevant therapeutic strategy for cancer. The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been proven, and radiolabeled peptides have been demonstrated to be effective in patients with malignant tumors. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of α(v)β(3) integrin, thereby inhibiting angio genesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable m ultimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of {sup 177}Lu-AuNP-RGD in athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas and compare with that of {sup 177}Lu-AuNP or {sup 177}Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-micro PET/CT), renal radiotoxicity, renal and tumoral histological characteristics as well as tumoral VEGF and HIF-1? gene expression (by realtime polymerase chain reaction) following treatment with {sup 177}Lu-AuNP-RGD, {sup 177}Lu-AuNP or {sup 177}Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, {sup 177}Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 ± 7.9 Gy) vs other treatments. These results correlated with the observed therapeutic response, in which {sup 177}Lu-AuNP-RGD significantly (p<0.05) reduced tumor progression, tumor metabolic activity, intratumoral vessels and VEGF gene expression compared to the other radiopharmaceuticals. This was consequence of high tumor retention and a combination of molecular targeting therapy (m ultimeric RGD system) and radiotherapy ({sup 177}Lu). There was a low uptake in non-target organs and no induction of renal toxicity. {sup 177}Lu-AuNP-RGD demonstrates properties suitable for use as an agent for molecular targeting radiotherapy. (Author)

  10. Peptide Receptor Radionuclide Therapy with (90)Y-DOTATOC and (177)Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this t...

  11. Nanocrystalline zirconia: a novel sorbent for the preparation of (188)W/(188)Re generator.

    Science.gov (United States)

    Chakravarty, Rubel; Shukla, Rakesh; Tyagi, A K; Dash, Ashutosh; Venkatesh, Meera

    2010-02-01

    Nanocrystalline zirconia, a novel high capacity sorbent material was synthesized and tested for its utility in the preparation of (188)W/(188)Re generators. The structural investigation of the material was carried out using X-ray diffraction, surface area determination, FTIR and TEM micrograph analysis. Various experimental parameters were optimized to separate (188)Re from (188)W. The capacity of the material was found to be approximately 325mgW/g at the optimum pH. A chromatographic (188)W/(188)Re generator was developed using this material from which >80% of (188)Re generated could be eluted with 0.9% saline solution, with high radionuclidic, radiochemical and chemical purity and appreciably high radioactive concentration suitable for radiopharmaceutical applications.

  12. External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Chang CH

    2015-05-01

    Full Text Available Chih-Hsien Chang,1,2 Shin-Yi Liu,3 Chih-Wen Chi,3 Hsiang-Lin Yu,1 Tsui-Jung Chang,1 Tung-Hu Tsai,4 Te-Wei Lee,1 Yu-Jen Chen3–5 1Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan; 2Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 3Department of Medical Research MacKay Memorial Hospital, 4Institute of Traditional Medicine, National Yang-Ming University, 5Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan Abstract: External beam radiotherapy (EBRT treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 (188Re-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma and CE81T/VGH (squamous cell carcinoma were implanted and compared. The radiochemical purity of 188Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the 188Re-liposome. The combination of EBRT and 188Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with 188Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of 188Re-liposome into feces and urine. In conclusion, the combination of EBRT with 188Re-liposome might be a potential treatment modality for esophageal cancer. Keywords: Radionuclide

  13. Application of analytic methodologies for image quantification in neuroendocrine tumor therapy with {sup 177}Lu-DOTA

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, T.T.A.; Oliveira, S.M.V. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Marco, L.; Mamede, M., E-mail: tadeukubo@gmail.com [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil)

    2012-07-01

    Neuroendocrine tumors have annual incidence of 1 to 2 cases per one hundred thousand inhabitants. The {sup 177}Lu-DOTA-octreotate treatments in 3 or 4 cycles has been effective in controlling disease progression and, in some cases, promote tumor remission. To estimate radiation side effects in healthy organs, image quantification techniques have been broadcast for individualized patient dosimetry. In this paper, image data processing methods are presented to allowing comparisons between different image conjugate views, combined with attenuation correction and system sensitivity. Images were acquired 24, 72 and 192 h after administration of 74 GBq of {sup 177}Lu-DOTA using a dual-head gamma camera detection system and they were evaluated with ImageJ software. 4 female patients underwent to two cycles of treatment. The kidneys, liver and whole-body regions of interest were separately assessed by 4 techniques for counts method and 12 techniques for pixel intensity method, considering the main photopeak separately and aided by the attenuation correction map and adjacent windows to photopeak energy. The pixel intensity method was combined with mathematical correction for pixels with null value. The results obtained by the two methods were strongly correlated (r>0.9) (p<0.001). The paired t-test accepted the null hypothesis of compatibility between the two methods (with and without attenuation correction map) (p<0.05), but rejected it when the adjacent windows were combined. No significant tumor reduction (p>0.05) was found between the treatment cycles. In conclusion, the pixel intensity method is faster and allows macros, minimizing operator error, and may optimize dosimetry in tumor therapies with {sup 177}Lu-DOTA-octreotate. (author)

  14. In vivo quantification of {sup 177}Lu with planar whole-body and SPECT/CT gamma camera imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, Dale L. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Faculty of Health Sciences, University of Sydney, Cumberland, NSW (Australia); Sydney Medical School, University of Sydney, Camperdown, NSW (Australia); NETwork, Sydney Vital, St Leonards, Sydney, NSW (Australia); Hennessy, Thomas M.; Willowson, Kathy P.; Henry, E. Courtney [Institute of Medical Physics, University of Sydney, Camperdown, NSW (Australia); Chan, David L.H. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); NETwork, Sydney Vital, St Leonards, Sydney, NSW (Australia); Aslani, Alireza [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Roach, Paul J. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Sydney Medical School, University of Sydney, Camperdown, NSW (Australia)

    2015-09-17

    Advances in gamma camera technology and the emergence of a number of new theranostic radiopharmaceutical pairings have re-awakened interest in in vivo quantification with single-photon-emitting radionuclides. We have implemented and validated methodology to provide quantitative imaging of {sup 177}Lu for 2D whole-body planar studies and for 3D tomographic imaging with single-photon emission computed tomography (SPECT)/CT. Whole-body planar scans were performed on subjects to whom a known amount of [{sup 177}Lu]-DOTA-octreotate had been administered for therapy. The total radioactivity estimated from the images was compared with the known amount of the radionuclide therapy administered. In separate studies, venous blood samples were withdrawn from subjects after administration of [{sup 177}Lu]-DOTA-octreotate while a SPECT acquisition was in progress and the concentration of the radionuclide in the venous blood sample compared with that estimated from large blood pool structures in the SPECT reconstruction. The total radioactivity contained within an internal SPECT calibration standard was also assessed. In the whole-body planar scans (n = 28), the estimated total body radioactivity was accurate to within +4.6 ± 5.9 % (range −17.1 to +11.2 %) of the correct value. In the SPECT reconstructions (n = 12), the radioactivity concentration in the cardiac blood pool was accurate to within −4.0 ± 7.8 % (range −16.1 to +7.5 %) of the true value and the internal standard measurements (n = 89) were within 2.0 ± 8.5 % (range −16.3 to +24.2 %) of the known amount of radioactivity contained. In our hands, state-of-the-art hybrid SPECT/CT gamma cameras were able to provide accurate estimates of in vivo radioactivity to better than, on average, ±10 % for use in biodistribution and radionuclide dosimetry calculations.

  15. Safety of multiple repeated cycles of {sup 177}Lu-octreotate in patients with recurrent neuroendocrine tumour

    Energy Technology Data Exchange (ETDEWEB)

    Yordanova, Anna; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin; Brossart, Peter [University Hospital Bonn, Department of Internal Medicine 3, Bonn (Germany); Gonzalez-Carmona, Maria A.; Strassburg, Christian P. [University Hospital Bonn, Department of Internal Medicine 1, Bonn (Germany)

    2017-07-15

    Peptide receptor radionuclide therapy (PRRT) is an effective therapy in patients with a somatostatin receptor-positive neuroendocrine tumour (NET). Still unclear is how many cycles of {sup 177}Lu-octreotate can be repeated while maintaining an acceptable toxicity profile. The purpose of this study was to assess the safety of repeated PRRT in patients with recurrent NET. We retrospectively evaluated data from 15 patients treated with repeated PRRT between 2004 and 2015. The median administered activity was 63.8 GBq (range 52-96.6 GBq) in a median of 9 cycles (range 8-13 cycles). Nonhaematological and haematological toxicities were assessed from clinical reports and laboratory data. The rates of adverse events in three therapy groups were compared: during cycles 1 to 4, cycles 5 to 8, and cycles 9 to 13. Baseline laboratory assessments were also compared with data obtained at the end of treatment. The overall survival in the study patients was compared with survival data in patients who received only a baseline PRRT of three or four cycles. We observed no life-threatening adverse events (CTC-4) during {sup 177}Lu-octreotate treatment. Reversible haematological toxicity (CTC-3) occurred in two patients (13%). No CTC-3/4 nephrotoxicity was recorded. More CTC-3 adverse events were recorded in the first therapy group than in the other two groups. Furthermore, there were no significant changes in the mean values of thrombocytes, leucocytes and serum creatinine before and after therapy. However, the mean haemoglobin levels fell from 14 g/dL to 11 g/dL. Finally, compared with those patients who received three or four cycles, there was a survival benefit in patients treated with repeated PRRT (censored overall survival 85.6 vs. 69.7 months, p < 0.001). Therapy with eight or more cycles of {sup 177}Lu-octreotate was well tolerated and led to a survival benefit in patients with recurrent NET. (orig.)

  16. Report on short-term side effects of treatments with {sup 177}Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Essen, Martijn van; Kam, Boen L.; Kwekkeboom, Dik J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Aken, Maarten O. van [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2008-04-15

    Treatment with the radiolabelled somatostatin analogue {sup 177}Lu-octreotate results in tumour remission in 47% of patients with gastroenteropancreatic neuroendocrine tumours. Adding capecitabine to {sup 177}Lu-octreotate, as a radio-sensitiser, may enhance these anti-tumour effects. We now present the short-term toxicity profile of this novel combination. Seven patients were treated with 7.4 GBq {sup 177}Lu-octreotate and capecitabine (1650 mg/m{sup 2} per day) for 2 weeks with an intended number of four cycles. Toxicity, and especially haematological and renal parameters, were monitored on a weekly basis for the first two cycles and 4 and 6 weeks after subsequent cycles. None of the patients had hand-foot syndrome. One patient had grade 1 stomatitis occurring after one of four cycles. Grade 3 or 4 leukopenia or neutropenia did not occur. One patient had grade 3 anaemia, but none had grade 4 anaemia. One patient had grade 2 thrombocytopenia after the fourth cycle, and one had grade 3 thrombocytopenia. Grade 4 thrombocytopenia did not occur. No significant changes in serum creatinine levels were observed. None of the patients had symptoms of cardiac ischaemia. Treatment with the combination of {sup 177}Lu-octreotate and capecitabine was feasible and safe considering acute and subacute side effects. We therefore started a randomised, controlled clinical trial to compare this combination with {sup 177}Lu-octreotate as single agent with regard to anti-tumour effects and side effects. (orig.)

  17. 188Re-LABELED HYPERBRANCHED POLYSULFONAMINE AS A ROBUST TOOL FOR TARGETED CANCER DIAGNOSIS AND RADIOIMMUNOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    Nan Li; Yue Jin; Li-zhe Xue; Pei-yong Li; De-yue Yan; Xin-yuan Zhu

    2013-01-01

    Hyperbranched polysulfonamine (HPSA) is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation.To realize the functionalization of HPSA,both N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) for tethering the human-mouse chimeric monoclonal antibody CH12 and N-hydroxy succinimidyl S-acetylmercaptoacetyltriglycinate (NHS-MAG3) for labeling 188Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages,attaining the SPDP-HPSA-MAG3 intermediate.In order to reserve the structural integrity of CH12,the fragment crystallizable (Fc) region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with N-(κ-maleimidoundecanoic acid) hydrazide (KMUH).After chelating 188Re with MAG3 group,the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region.As a result,both the epidermal growth factor receptor vIII (EGFRvIII) targeted monoclonal antibody CH12 and the radionuclide 188Re were conjugated to the HPSA-based vehicles,forming the 188Re-labeled and CH12-tethered HPSA (CH12-HPSA-188Re).The molecular weight and in vitro stability of CH12-HPSA-l88Re were evaluated by gel electrophoresis and paper chromatography.On one hand,the CH12-HPSA-188Re could specifically bind to the EGFRvIII-positive human hepatocarcinoma cells in vitro.On the other hand,it could also target at the tumor tissue of nude mice in vivo.Hence,the CH12-HPSA-188Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.

  18. Evaluation of 188Re-DTPA-deoxyglucose as a potential cancer radiopharmaceutical.

    Science.gov (United States)

    Chen, Yue; Xiong, Qing-Feng; Yang, Xi-Qun; He, Ling; Huang, Zhan-Wen

    2010-03-01

    We aimed to synthesize diethylenetriamine pentaacetic acid-deoxyglucose (DTPA-DG) radiolabeled with (188)Re and to evaluate its biologic characteristics using mammary tumor-bearing mice. The biodistribution of the radiolabeled compound was determined by tissue counting at 3, 12, and 24 hours after injection in experimental animals. Scintigraphic examinations of nude mice bearing breast cancer (MCF-7 cells) were performed after (188)Re-DTPA-DG (18.5 MBq) was injected in the tail vein. For the tumor inhibitory portion of this work, tumor volumes were measured and recorded every 3 days until the 21st day after injection. The radiochemical purity of (188)Re-DTPA-DG was 95.0%. Based on biodistribution measurements, (188)Re-DTPA-DG was taken up at high levels by the tumor. The mean tumoral percent injected dosages per gram (% ID/g) were 1.98 +/- 0.29 (SD), 2.89 +/- 0.43, and 0.42 +/- 0.06 % ID/g at 3, 12, and 24 hours, respectively, after injection. In the (188)Re-DTPA-DG scintigraphic examinations, the tumors were clearly delineated on the images recorded 2, 4, 8, 12, and 24 hours after injection. In the tumor inhibitory evaluations, the tumor volume of the (188)Re-DTPA-DG-treated group increased more slowly than that of the control groups, which were treated with (188)Re-perrhenate or saline (p DTPA-DG showed excellent tumor targeting and tumor growth suppression properties on MCF-7 tumor cells. Rhenium-188-DTPA-DG may be a potential agent for the diagnosis and radiotherapy of tumors.

  19. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, M. A de; Pedraza L, M. [Department of Nuclear Medicine, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Rodriguez C, J. [Faculty of Medicine, UAEM, Toluca, Estado de Mexico (Mexico); Ferro F, G. [ININ, 52045 Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, Mexico D.F. (Mexico)

    2006-07-01

    Malignant pancreas tumours induced in athymic mice are a good model for targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses and to evaluate {sup 177}Lu-DOTA-TATE as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells, which over-express somatostatin receptors, were injected in athymic mice and 20 days later the mean tumour size was 3.08 square cm (n=3). A mean of 86.3 MBq {sup 177}Lu-DOTA-TATE, was injected in a tail vein and 19 days after therapy the size of the tumours was 0.81 square cm. There was a partial relapse and after 16 days, when sacrificed, the mean tumour size was 8.28 cubic cm. An epithelial and sarcoma mixed tumour in the kidney of one treated mouse was found. The tumour of the control mouse was 8.61 cubic cm when sacrificed 14 days after tumour induction. Radiotherapy estimates to the tumours was 35.9-39.7 Gy and the tumours might have been completely reduced with a second therapy dose. These preliminary studies justify further therapeutic and dosimetry estimations to ensure that Lu-{sup 177}-DOTA-TATE will act as expected in man, considering kidney radiation. (Author)

  20. Preparation and preliminary studies on {sup 177}Lu-labeled hydroxyapatite particles for possible use in the therapy of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sudipta; Das, Tapas [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Sarma, Haladhar D. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Venkatesh, Meera [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Banerjee, Sharmila [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)], E-mail: sharmila@barc.gov.in

    2008-07-15

    Introduction: Intra-arterial administration of particulates labeled with suitable {beta}{sup -}-emitting radionuclides has emerged as one of the most successful modality for the treatment of primary and metastatic liver cancer. {sup 177}Lu [T{sub 1/2}=6.73 d, E{sub {beta}}(max)=0.49 MeV, E{sub {gamma}}=208 keV (11%)] could be envisaged as a viable radionuclide for use in liver cancer therapy with wider acceptability owing to its feasibility of production in large-scale and relatively longer half-life providing logistic advantages. Hydroxyapatite (HA) particles of 20-60 {mu}m size range are chosen as the particulate carrier due to its excellent biocompatibility and ease of labeling with lanthanides. Methods: {sup 177}Lu was produced by thermal neutron bombardment on enriched Lu target. HA particles of desired size range were synthesized and characterized. Radiolabeling of HA particles was achieved at room temperatures within 30 min. The biological behavior of {sup 177}Lu-labeled HA particles prepared under optimized conditions was tested in Wistar rats. Results: {sup 177}Lu was produced with a specific activity of 444.2{+-}41.8 GBq/mg and radionuclidic purity of 99.98%. {sup 177}Lu-HA was prepared with high radiochemical purity of >99%, and the radiolabeled agent showed excellent in vitro stability. The agent exhibited {approx}73% retention of injected activity in liver after 14 days postadministration with insignificant uptake in any other major organ/tissue except skeleton in biodistribution and imaging studies. Conclusion: {sup 177}Lu-HA exhibited promising features in radiochemical studies. However, preliminary biodistribution studies in normal Wistar rats exhibited suboptimum liver retention and an undesirable skeletal uptake.

  1. Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kwon Joong Yong

    2016-05-01

    Full Text Available Radiolabeled antibodies (mAbs provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day a suitable radionuclide for radioimmunotherapy (RIT of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB, caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease.

  2. Labeling internalizing anti-epidermal growth factor receptor variant III monoclonal antibody with {sup 177}Lu: in vitro comparison of acyclic and macrocyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hens, Marc; Vaidyanathan, Ganesan; Welsh, Phil [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)], E-mail: zalut001@mc.duke.edu

    2009-02-15

    Introduction: The monoclonal antibody (mAb) L8A4, reactive with the epidermal growth factor receptor variant III (EGFRvIII), internalizes rapidly in glioma cells after receptor binding. Combining this tumor-specific mAb with the low-energy {beta}-emitter {sup 177}Lu would be an attractive approach for brain tumor radioimmunotherapy, provided that trapping of the radionuclide in tumor cells after mAb intracellular processing could be maximized. Materials and Methods: L8A4 mAb was labeled with {sup 177}Lu using the acyclic ligands [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S) -cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA), 2-(4-isothiocyanatobenzyl)-diethylenetriaminepenta-acetic acid (pSCN-Bz-DTPA) and 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and {alpha}-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (MeO-DOTA). Paired-label internalization and cellular processing assays were performed on EGFRvIII-expressing U87.{delta}EGFR glioma cells over 24 h to directly compare {sup 177}Lu-labeled L8A4 to L8A4 labeled with {sup 125}I using either iodogen or N-succinimidyl 4-guanidinomethyl-3-[{sup 125}I]iodobenzoate ([{sup 125}I]SGMIB). In order to facilitate comparison of labeling methods, the primary parameter evaluated was the ratio of {sup 177}Lu to {sup 125}I activity retained in U87.{delta}EGFR cells. Results: All chelates demonstrated higher retention of internalized activity compared with mAb labeled using iodogen, with {sup 177}Lu/{sup 125}I ratios of >20 observed for the three DTPA chelates at 24 h. When compared to L8A4 labeled using SGMIB, except for MeO-DOTA, internalized activity for {sup 125}I was higher than {sup 177}Lu from 1-8 h with the opposite behavior observed thereafter. At 24 h, {sup 177}Lu/{sup 125}I ratios were between 1

  3. High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

    2016-03-15

    Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

  4. Renal function affects absorbed dose to the kidneys and haematological toxicity during {sup 177}Lu-DOTATATE treatment

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Johanna; Berg, Gertrud [Sahlgrenska University Hospital, Department of Oncology, Goeteborg (Sweden); Waengberg, Bo [Sahlgrenska University Hospital, Department of Surgery, Goeteborg (Sweden); Larsson, Maria [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Forssell-Aronsson, Eva; Bernhardt, Peter [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengineering, Goeteborg (Sweden)

    2015-05-01

    Peptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment. The study included 51 patients with an advanced neuroendocrine tumour who received {sup 177}Lu-DOTATATE treatment during 2006 - 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 - 8.2 GBq) was given at intervals of 6 - 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated. A significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of {sup 177}Lu in the whole body (range 0.89 - 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53). Patients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during {sup 177}Lu-DOTATATE treatment. The study confirms the

  5. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with {sup 177}Lu-octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [Charite, University Medicine Berlin, Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Berlin (Germany); Nagarajah, James [University Hospital, Department of Nuclear Medicine, Essen (Germany)

    2014-03-15

    Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine - allowing only approximate estimates of GFR - the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with {sup 177}Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by {sup 99m}Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m{sup 2} per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m{sup 2} per year) and 16 patients (22 %) a significant (>10 ml/min/m{sup 2} per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m{sup 2} per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of

  6. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE: the IEO phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M.; Baio, Silvia M.; Lombardo, Dario; Chinol, Marco; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta; Ferrari, Mahila E. [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Fazio, Nicola [European Institute of Oncology, Division of Medical Oncology, Milan (Italy); Iodice, Simona [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Bartolomei, Mirco [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); M. Bufalini Hospital, Division of Nuclear Medicine, Cesena, FC (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Unit of Radiometabolic Medicine, Meldola, FC (Italy)

    2011-12-15

    Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst{sub 2}), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of {sup 177}Lu-DOTATATE in multiple cycles. Fifty-one consecutive patients with unresectable/metastatic sst{sub 2}-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of {sup 177}Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. {sup 177}Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. (orig.)

  7. Preparation of {sup 188}Re-lanreotide peptide and its quality control

    Energy Technology Data Exchange (ETDEWEB)

    Mushtaq, A.; Pervez, S.; Haider, I. [Pakistan Inst. of Nuclear Science and Technology, Islamabad (Pakistan). Nuclear Chemistry Div.

    2000-07-01

    A simple method is described for the preparation of {sup 188}Re-Lanreotide, a radiolabeled synthetic peptide derived from an analogue of somatostatin, using Lanreotide (50 {mu}g) and stannous tartrate to which is added carrier-free {sup 188}Re. The radiolabeling has been carried out with {proportional_to}555 MBq (15 mCi) with a > 95% labeling efficiency and no need for subsequent purification. ITLC and HPLC techniques were employed for monitoring the stability and labeling yield. Radiolabeling results in one major peak when analyzed by reverse-phase (RP) HPLC. (orig.)

  8. Effects of therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate on endocrine function

    Energy Technology Data Exchange (ETDEWEB)

    Teunissen, Jaap J.M.; Kwekkeboom, Dik J. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Jong, Frank H. de; Feelders, Richard A.; Aken, Maarten O. van; Herder, Wouter W. de [Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Rijke, Yolanda B. de [Erasmus Medical Center, Department of Clinical Chemistry, Rotterdam (Netherlands)

    2009-11-15

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 {+-} 16 to 25 {+-} 4 ng/l, p < 0.05) and follicle-stimulating hormone (FSH) levels increased (5.9 {+-} 0.5 to 22.7 {+-} 1.4 IU/l, p < 0.05). These levels returned to near baseline levels. Total testosterone and sex hormone binding globulin (SHBG) levels decreased (15.0 {+-} 0.9 to 10.6 {+-} 1.0 nmol/l, p < 0.05 and 61.8 {+-} 8.7 to 33.2 {+-} 3.7 nmol, p < 0.05), respectively, whereas non-SHBG-bound T did not change. An increase (5.2 {+-} 0.6 to 7.7 {+-} 0.7 IU/l, p < 0.05) of luteinizing hormone (LH) levels was found at 3 months of follow-up returning to baseline levels thereafter. In 21 postmenopausal women, a decrease in levels of FSH (74.4 {+-} 5.6 to 62.4 {+-} 7.7 IU/l, p < 0.05) and LH (26.8 {+-} 2.1 to 21.1 {+-} 3.0 IU/l, p < 0.05) was found. Of 66 patients, 2 developed persistent primary hypothyroidism. Free thyroxine (FT{sub 4}) levels decreased (17.7 {+-} 0.4 to 15.6 {+-} 0.6 pmol/l, p < 0.05), whereas thyroid-stimulating hormone (TSH) and triiodothyronine (T{sub 3}) levels did not change. Reverse triiodothyronine (rT{sub 3}) levels decreased (0.38 {+-} 0.03 to 0.30 {+-} 0.01 nmol/l, p < 0.05). Before and after therapy adrenocorticotropic hormone (ACTH) stimulation tests showed an adequate response of serum cortisol (> 550 nmol/l, n = 18). Five patients developed elevated HbA{sub 1c} levels (> 6.5%). In men {sup 177}Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non

  9. {sup 177}Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Rajabi, Hossein, E-mail: hrajabi@modares.ac.i [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Babaei, Mohammad Hossein; Daha, Fariba Johari [Department of Radioisotope, Nuclear Science and Technology Research Institute, 14115-331 Tehran (Iran, Islamic Republic of)

    2010-11-15

    Introduction: In the present study, Herceptin was labeled with lutetium-177 via DOTA, and the necessary preclinical quality control tests (in vitro and in vivo) were performed to evaluate its use as a radioimmunotherapy agent. Material and Methods: Herceptin was conjugated to DOTA as a chelator in three different conjugation buffers (ammonium acetate, carbonate and HEPES buffer); each of the resulting conjugates was compared with respect to in vitro characteristics such as number of chelates per antibody, incorporated activity, immunoreactivity and in vitro stability in PBS buffer and blood serum. The biodistribution study and gamma camera imaging were performed in mice bearing breast tumors. To assess the therapeutic effects of {sup 177}Lu-Herceptin, cytotoxicity was investigated for 7 days in a SKBr3 breast cancer cell line. Results: Carbonate buffer was the best conjugation buffer (number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81%, after 4 days). The efficient tumor uptake observed in the biodistribution studies was consistent with the gamma camera image results. At a concentration of 4 {mu}g ml{sup -1}, {sup 177}Lu-Herceptin (surviving cells: 5{+-}0.6% of the total cells) of the total cells corresponded to an approximately eightfold increase in cytotoxicity in comparison to unmodified Herceptin (surviving cells: 43{+-}3.9%). Conclusion: The new complex described herein could be considered for further evaluation in animals and potentially in humans as a radiopharmaceutical for use in the radioimmunotherapy of breast cancer. These results may be important for patients who cannot tolerate the therapeutic dosage of Herceptin currently used because of heart problems.

  10. Outcome and toxicity of salvage therapy with {sup 177}Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Haslerud, Torjan; Sabet, Amin; Ahmadzadehfar, Hojjat; Guhlke, Stefan; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [University Medicine Berlin, Department of Hepatology and Gastroenterology, Charite, Campus Virchow Clinic, Berlin (Germany); Gruenwald, Frank [University Hospital, Department of Nuclear Medicine, Frankfurt (Germany)

    2014-02-15

    We assessed the outcome and toxicity of salvage therapy (repeat treatment) with {sup 177}Lu-octreotate and high cumulative activities in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET). We retrospectively analysed a consecutive cohort of 33 patients with metastatic GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our institution. All patients had progressive NET prior to salvage treatment and had shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq (30.0-83.7 GBq). Radiographic response was assessed using CT and/or MRI according to modified SWOG criteria. Toxicity was evaluated using laboratory data, including complete blood counts and renal function tests using CTCAE 3.0. Survival analysis was performed with the Kaplan-Meier curve method and a significance level at p < 0.05. Radiographic responses consisted of complete response in 1 patient (3.0 %), partial response in 6 patients (18.2 %), minor response in 1 patient (3.0 %), stable disease in 14 patients (42.4 %), and progressive disease in 11 patients (33.3 %). Median progression-free survival (PFS) from the start of salvage therapy was 13 months (95 % CI 9-18) and patients with a history of a durable PFS after initial PRRT tended to have long-lasting PFS after salvage treatment (p = 0.04). None of the patients developed severe nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up. Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients (21.2 %). The cumulative administered activity was not associated with an increased incidence of haematotoxicity. PRRT with {sup 177}Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET. (orig.)

  11. An approach for conjugation of 177 Lu- DOTA-SCN- Rituximab (BioSim & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients

    Directory of Open Access Journals (Sweden)

    Parul Thakral

    2014-01-01

    Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim in patients of relapsed and refractory non Hodgkin′s lymphoma can be considered.

  12. Preliminary study of metabolic radiotherapy with {sup 188}Re via small animal imaging

    Energy Technology Data Exchange (ETDEWEB)

    Antoccia, A. [Dept. of Biology, Univ. Roma3, V.le G. Marconi, I-00146 Rome (Italy); INFN, Sezione Roma3, Via della Vasca Navale 84, I-00146 Rome (Italy); Baldazzi, G. [Dept. of Physics, Univ. Bologna, V.le C. Berti-Pichat 6/2, I-40127 Bologna (Italy); INFN, Sezione Bologna, V.le C. Berti-Pichat 6/2, I-40127 Bologna (Italy); Bello, M. [Dept. of Physics, Univ. Padova, Via F. Marzolo 8, I-35131 Padova (Italy); INFN - LNL, V.le dell' Universita 2, I-35020 Legnaro(Italy)

    2006-01-15

    {sup 188}Re is a {beta}{sup -} (Emax=2.12 MeV) and {gamma} (155 keV) emitter. Since its chemistry is similar to that of the largely employed tracer, {sup 99m}Tc, molecules of hyaluronic acid (HA) have been labelled with {sup 188}Re to produce a target specific radiopharmaceutical. The radiolabeled compound, i.v. injected in healthy mice, is able to accumulate into the liver after a few minutes. To study the effect of metabolic radiotherapy in mice, we have built a small gamma camera based on a matrix of YAP:Ce crystals, with 0.6x0.6x10 mm{sup 3} pixels, read out by a R2486 Hamamatsu PSPMT. A high-sensitivity 20 mm thick lead parallel-hole collimator, with hole diameter 1.5 mm and septa of 0.18 mm, is placed in front of the YAP matrix. Preliminary results obtained with various phantoms containing a solution of {sup 188}Re and with C57 black mice injected with the {sup 188}Re-HA solution are presented. To increase the space resolution and to obtain two orthogonal projections simultaneously we are building in parallel two new cameras to be positioned at 90 degrees. They use a CsI(Tl) matrix with 1x1x5 mm{sup 3} pixels read out by H8500 Hamamatsu Flat panel PMT.

  13. Preliminary study of metabolic radiotherapy with 188Re via small animal imaging

    CERN Document Server

    Baldazzi, G; Muciaccio, A; Navarria, Francesco Luigi; Pancaldi, G; Perrotta, A; Zuffa, M; Boccaccio, P; Uzunov, N; Bello, M; Bernardini, D; Mazzi, U; Moschini, G; Riondato, M; Rosato, A; Garibaldi, F; Pani, R; Antoccia, A; De Notaristefani, F; Hull, G; Cencelli, V O; Sgura, A; Tanzarella, C

    2006-01-01

    188Re is a beta- (Emax = 2.12 MeV) and gamma (155 keV) emitter. Since its chemistry is similar to that of the largely employed tracer, 99mTc, molecules of hyaluronic acid (HA) have been labelled with 188Re to produce a target specific radiopharmaceutical. The radiolabeled compound, i.v. injected in healthy mice, is able to accumulate into the liver after a few minutes. To study the effect of metabolic radiotherapy in mice, we have built a small gamma camera based on a matrix of YAP:Ce crystals, with 0.6x0.6x10 mm**3 pixels, read out by a R2486 Hamamatsu PSPMT. A high-sensitivity 20 mm thick lead parallel-hole collimator, with hole diameter 1.5 mm and septa of 0.18 mm, is placed in front of the YAP matrix. Preliminary results obtained with various phantoms containing a solution of 188Re and with C57 black mice injected with the 188Re-HA solution are presented. To increase the space resolution and to obtain two orthogonal projections simultaneously we are building in parallel two new cameras to be positioned at...

  14. Formulation, radiopharmaceutical kinetics and dosimetry of the {sup 188}Re(V)-DMSA complex; Formulacion, radiofarmacocinetica y dosimetria del complejo {sup 188}Re(V)-DMSA

    Energy Technology Data Exchange (ETDEWEB)

    Garcia S, L.; Ferro F, G. [Departamento de Materiales Radiactivos. Instituto Nacional de Investigaciones Nucleares, C.P. 52045 Salazar, Estado de Mexico (Mexico); Murphy, C.A. de; Pedraza L, M. [Departamento de Medicina Nuclear, Instituto Nacional de la Nutricion, Salvador Zubiran, Mexico D.F. (Mexico); Azorin N, J. [Departamento de Fisica, Universidad Autonoma Metropolitana Iztapalapa, Mexico D.F. (Mexico)

    1999-07-01

    It was developed through experimental design (ANOVA), a formulation to prepare the {sup 188} Re(V)-Dmsa complex. Likewise, there were realized studies of radiopharmaceutical kinetics and internal dosimetry in animals, its normal and with induced tumors, considering an open bi compartmental model using the MIRD methodology. The {sup 188} Re(V)-Dmsa complex was obtained with a radiochemical purity greater than 95% incubating 30 min at 90 Centigrade under the following formulation: [SnCl{sub 2}] = 1.4 mg/ml, [ascorbic acid] = 0.5 mg/ml, p H = 2.0 - 3.0. The stability test of the formulation, shows that after 48 h of its preparation, does not produce radiolytic degradation neither chemical decomposition. The radiopharmaceutical kinetics data show an average residence time 7.2h, velocity constant {alpha} = 0.6508h{sup -1} and {beta} = 0.1046 h{sup -1} with an apparent distribution volume 6.9 l. The main elimination via was renal and it was observed osseous caption with an accumulated activity 522.049 {+-} 62 MBq h (residence time 14.1094 {+-} 1.69h). In according with the dosimetric calculations, by each 37 MBq injected, the equivalent dose at the tumor was 9.67{+-} 0.33 Sv/g, for an effective dose 0.292 {+-} 0.0017 mSv/MBq. The images obtained in the gamma camera of the mice with induced tumors, show that do not have significant accumulation in the metabolic organs. The caption in bone and in tumors induced of the {sup 188} Re(V)-Dmsa complex, show its potential for be used as a palliative agent for pain in patients with osseous metastasis and in the treatment of tumors of soft tissue. (Author)

  15. Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with {sup 177}Lu for tumors therapy that expressing αβ integrin s; Sistema monomerico, dimerico y multimerico de peptidos de RGD radiomarcados con {sup 177}Lu para terapia de tumores que expresan integrinas αβ

    Energy Technology Data Exchange (ETDEWEB)

    Luna G, M. A.

    2014-07-01

    The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high affinity agents for the α(v)β(3) and α(v)β(5) integrin. The aim of this research was to prepare a multimeric system of {sup 177}Lu-labeled gold nanoparticles conjugated to c[RGDfK(C)] [cyclo(Arg-Gly-Asp-Phe-Lys(Cys)] peptides and to compare the radiation absorbed dose with that of {sup 177}Lu-labeled monomeric and dimeric RGD peptides to α(v)β(3) integrin-positive U87MG tumors in mice, as well as, evaluate the in vitro potential {sup 177}Lu-AuNP-c[RGDfK(C)] as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. DOTA-GGC (1,4,7,10-tetraaza cyclododecane-N,N,N-tetraacetic-Gly-Gly-Cys) and c[RGDfK(C)] peptides were synthesized and conjugated to AuNPs by the spontaneous reaction of the thiol groups. Tem, UV-Vis, XP S, Raman and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. To obtain {sup 177}Lu-AuNP-c[RGDfK(C)], the {sup 177}Lu-DOTA-GGC radio peptide was first prepared and added to a solution of AuNPs followed by c[RGDfK(C)] (25 μL, 5 μM) at 18 grades C for 15 min. {sup 177}Lu-DOTA-GGC, {sup 177}Lu- DOTA-cRGDfK and {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} were prepared by adding {sup 177}LuCl{sub 3} (370 MBq) to 5 μL (1 mg/ml) of the DOTA derivative diluted with 50 μL of 1 M acetate buffer at ph 5. The mixture was incubated at 90 grades C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 grades C, compared to 40.3 grades C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with {sup 177}Lu

  16. Labeling of MDP with {sup 188}Re for bone tumour therapy

    Energy Technology Data Exchange (ETDEWEB)

    Barbezan, Angelica B.; Osso Junior, Joao A., E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    {sup 188}Re is one of the most attractive radioisotopes for a variety of therapeutic applications in nuclear medicine, due to its physical decay properties, such as {beta}{sup -} emission of 2.12 MeV, {gamma} emission of 155 keV and half life of 16.9 hours. Biphosphonates are potent inhibitors of osteoclastic bone resorption and are effective in several diseases that cause bone fragility and bone metastases. Because of these characteristics, labeled biphosphonates have been studied for bone pathologies, also acting as palliation of bone pain in case of metastasis.The aim of this study was to optimize the labeling of a phosphonate-MDP (Sodium Methylene Diphosphonate) with {sup 188}Re for use in bone pain palliation. {sup 188}Re was obtained by eluting a {sup 188}W-{sup 188}Re generator from POLATOM. The labeling was performed at room temperature using MDP, SnCl{sub 2} as reducing agent and ascorbic acid. The variables studied were: Mass of ligand (3, 6 and 10 mg), reducing agent mass (5, 7, 10 and 11 mg), ascorbic acid mass (1, 3, 5 and 6 mg), pH (1 and 2) and time of reaction (15, 60, 120, 360 and 4320 minutes), that also reflected the stability of the radiopharmaceutical. The radiochemical control, that also measures the labeling efficiency was evaluated by paper chromatography using Whatman 3MM paper and the solvents acetone and 0.9%NaCl. The best formulation was the following: Mass of ligand MDP: 10 mg, mass of SnCl{sub 2}: 5 mg, ascorbic acid mass: 3 mg, time of reaction: 30 minutes, pH: 1. Under optimum conditions, {sup 188}Re MDP radiolabeling yield was 98,07% and the radiopharmaceutical was stable up to 72 h. (author)

  17. Dosimetric evaluation of anti-CD20 labelled with {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, Graciela; Osso Junior, Joao A., E-mail: gracielabarrio@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Radioimmunotherapy has the potential to deliver lethal radiation energy directly to malignant cells via targeting of radioisotope-conjugated monoclonal antibodies (MAbs) to specific antigens. B-cell lymphoma is a particularly good candidate for radioimmunotherapy because the disease is inherently radiosensitive, malignant cells in the blood, bone marrow, spleen and lymphonodes are accessible, and MAbs have been developed to B-cell surface antigens that do not shed or modulate. Rituximab (RTX), the human IgG1-type chimeric form of the parent murine antibody ibritumomab, is specifically targeted against CD20, a surface antigen expressed by pre-B and mature human B lymphocytes. The use of rhenium-188 from a {sup 188}W/{sup 188}Re generator system represents an attractive alternative radionuclide for therapy. {sup 188}Re is produced from beta decay of the {sup 188}W parent. In addition to the emission of high-energy electrons (E{beta}= 2118 keV), {sup 188}Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of {sup 188}Re, the emission of gamma photon is an added advantage since the biodistribution of {sup 188}Re-labeled antibodies can be evaluated in vivo with a gamma camera. Also, rhenium has chemical properties similar to technetium. Thus, both can be conjugated to antibodies using similar chemistry methods. The objective of this work is to prove the usefulness of this radiopharmaceutical based on dosimetric studies, that are also required by the Brazilian Regulatory Agency (ANVISA). (author)

  18. Assessment of 188Re marked anti MHC class Ⅱ antibody by peripheral blood mononuclear cells stimulated by donor alloantigen

    Institute of Scientific and Technical Information of China (English)

    DING Guo-ping; CAO Li-ping; LIU Jie; LIU Da-ren; QUE Ri-sheng; ZHU Lin-hua; ZHOU Yi-ming; MAO Ke-jie; HU Jun-an

    2011-01-01

    Background Previous studies showed that anti MHC-Ⅱ monoclone antibody (MAb) only had partial inhibiting effect of alloreactive mixed lymphocyte reaction (MLR) in vitro and it was unsteady and non-persistent. The aim of this research was to determine whether radioactive isotope 188Re marked MHC-Ⅱ antibody could benefit the allograft acceptance in transplantation as compared to normal MHC-Ⅱ antibody.Methods 188Re was incorporated to 2E9/13F(ab')2 which is against swine MHC class Ⅱ antigen (MAb-188Re). Porcine peripheral blood mononuclear (PBMC) cells were examined for proliferation and cytokine mRNA expression after stimulation with MHC-Ⅱ MAb or MAb-188Re.Results The proliferative response of recipient PBMCs in mixed lymphocyte reaction (MLR) to donor alloantigen showed that the stimulation index of MAb-188Re group was significantly lower than the MHC-Ⅱ MAb group and control (P<0.05). mRNA expression of interleukin 2, interferon Y and tumor necrosis factor α (type 1 cytokines) was lower in MAb-188Re group than the MHC-Ⅱ MAb group, while interleukin 10 (type 2 cytokines) was higher in MAb-188Re group in the first 24 hours.Conclusion MAb-188Re could help the graft acceptance by inhibiting T cell proliferation, lowering the expression of type 1 cytokines and elevating the type 2 cytokines produced by PBMC.

  19. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC, Department of Pathology, Rotterdam (Netherlands)

    2007-05-15

    In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Male Lewis rats were injected with 278 or 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of {sup 99m}Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of {sup 99m}Tc-DMSA SPECT scintigrams at 130 days after [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate therapy correlated well with 1/creatinine (r {sup 2} = 0.772, p < 0.001). Amifostine and lysine effectively decreased functional renal damage caused by high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well

  20. DOTA conjugate with an albumin-binding entity enables the first folic acid-targeted 177Lu-radionuclide tumor therapy in mice.

    Science.gov (United States)

    Müller, Cristina; Struthers, Harriet; Winiger, Christian; Zhernosekov, Konstantin; Schibli, Roger

    2013-01-01

    The folate receptor (FR) has proven a valuable target for nuclear imaging using folic acid radioconjugates. However, using folate-based radiopharmaceuticals for therapy has long been regarded as an unattainable goal because of their considerable renal accumulation. Herein, we present a novel strategy in which a DOTA-folate conjugate with an albumin-binding entity (cm09) was designed with the aim of prolonging circulation in the blood and therewith potentially improving tumor-to-kidney ratios. The folate conjugate cm09 was radiolabeled with (177)LuCl(3), and stability experiments were performed in plasma. Cell uptake studies were performed on FR-positive KB tumor cells, and an ultrafiltration assay was used to determine the plasma protein-binding properties of (177)Lu-cm09. In vivo, (177)Lu-cm09 was tested in KB tumor-bearing mice using SPECT/CT. The therapeutic anticancer effect of (177)Lu-cm09 (20 MBq) applied as a single injection or as fractionated injections was investigated in different groups of mice (n = 5) by monitoring tumor size and the survival time of treated mice, compared with untreated controls. Compound cm09 was radiolabeled at a specific activity of 40 MBq/nmol, a radiochemical yield of more than 98%, and a stability of more than 99% over 5 d in plasma. Ultrafiltration revealed significant binding of (177)Lu-cm09 to serum proteins (∼91%) in plasma, compared with folate radioconjugate without an albumin-binding entity. Cell uptake and internalization of (177)Lu-cm09 was FR-specific and comparable to other folate radioconjugates. In vivo studies resulted in high tumor uptake (17.56 percentage injected dose per gram [%ID/g] at 4 h after injection), which was almost completely retained for at least 72 h. Renal accumulation was significantly reduced (28 %ID/g at 4 h after injection), compared with folate conjugates that lack an albumin-binding entity (∼70 %ID/g at 4 h after injection). These circumstances enabled SPECT imaging of excellent quality

  1. Preparation and quality control of clinic scale {sup 188}W-{sup 188}Re generator

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Duanzhi; Zhou, Wei [Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Applied Physics; Hu, Weiqing; He, Weiyu; Zhang, Lei; Min, Xiafeng; Shi, Xichang; Cao, Benhong [Amersham Kexin Pharmaceutical Co. Ltd, Shanghai (China); Wang, Yongxian [Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Applied Physics; Amersham Kexin Pharmaceutical Co. Ltd, Shanghai (China)

    2004-07-01

    {sup 188}Re is an excellent candidate for the radionuclide therapy, since it is easily obtained as a ''no-carrier-added'' radioisotope from a {sup 188}W-{sup 188}Re generator. The half-life of 16.9 hours is suitable for tumor treatment and of benefit to minimize toxicity to whole body; Beta emissions with energies of 2.12 MeV (71.6%) and 1.97 MeV (25.1%) are suitable for therapy and the gamma emission of 155 keV (15%) allows imaging and dosimetry. The drug for tumor therapy has been a highlight of the new drug development in recent years. The radionuclide therapy has shown significant effectiveness in the treatment of various cancers. {sup 188}W-{sup 188}Re generator could conveniently provide high levels of carrier-free rhenium-188 at low cost for the treatment of a variety of cancers, cardiovascular diseases as well as the marrow transplantation. (orig.)

  2. In vivo examination of {sup 188}Re(I)-tricarbonyl-labeled trastuzumab to target HER2-overexpressing breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, K.-T. [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Longtan 32546, Taiwan (China); Lo, Jem-Mau [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China)], E-mail: jmlo@mx.nthu.edu.tw

    2009-05-15

    Introduction: Trastuzumab (Herceptin), a humanized IgG1 monoclonal antibody directed against the extracellular domain of the HER2 protein, acts as an immunotherapeutic agent for HER2-overexpressing human breast cancers. Radiolabeled trastuzumab with {beta}- or {alpha} emitters can be used as radioimmunotherapeutic agent for the similar purpose but with additional radiation effect. Methods: In this study, trastuzumab was labeled with {sup 188}Re for radioimmunotherapy of HER2/neu-positive breast cancer. {sup 188}Re(I)-tricarbonyl ion, [{sup 188}Re(OH{sub 2}){sub 3}(CO){sub 3}]{sup +}, was employed as a precursor for directly labeling the monoclonal antibody with {sup 188}Re. The immunoreactivity of {sup 188}Re(I)-trastuzumab was estimated by competition receptor-binding assay using HER2/neu-overexpressive BT-474 human breast cancer cells. The localization properties of {sup 188}Re(I)-trastuzumab within both tumor and normal tissues of athymic mice bearing BT-474 human breast cancer xenografts (HER2/neu-overexpressive) and similar mice bearing MCF-7 human breast cancer xenografts (HER2/neu-low expressive) were investigated. Results: When incubated with human serum albumin and histidine at 25{sup o}C, {sup 188}Re(I)-trastuzumab was found to be stable within 24 h. The IC{sub 50} of {sup 188}Re(I)-trastuzumab was found to be 22.63{+-}4.57 nM. {sup 188}Re(I)-trastuzumab was shown to accumulate specifically in BT-474 tumor tissue in in vivo biodistribution studies. By microSPECT/CT, the image of {sup 188}Re localized BT-474 tumor was clearly visualized within 24 h. In contrast, {sup 188}Re(I)-trastuzumab uptake in HER2-low-expressing MCF-7 tumor was minimal, and the {sup 188}Re image at the localization of the tumor was dim. Conclusion: These results reveal that {sup 188}Re(I)-trastuzumab could be an appropriate radioimmunotherapeutic agent for the treatment of HER2/neu-overexpressing cancers.

  3. Preparation and Preliminary Biological Evaluation of {sup 177}Lu-DOTA folate as Potential Folate Receptor Targeting Therapeutic Agent

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kang-Hyuk; Hong, Young-Don; Pyun, Mi-Sun; Lee, So-Young; Felipe, Fenelope; Yoon, Sun-Ha; Choi, Sun-Ju [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-10-15

    Folic Acid (FA) and FA derivatives are overexpressed on several tumor cells. The cell-membrane folic acid receptors are known to be responsible for the cellular accumulation of FA and FA analogs, such as methotrexate and folic acid. Folate has been characterized to have high affinity for the folate-receptor positive cells and tissues and considered to be useful as diagnostic imaging and therapeutic agent. In 1940s, Folate analogue, aminopterin, was first used for treatment of leukemia and recently, many folate derivatives were tried for cancer-treatment agent as well as visualization of folate receptor. Many researchers tried to conjugate folic acid with macromolecules or low molecular weight chelators through its alpha or gamma carboxylate. However, despite the reduced binding affinity, FAs are still recognized by the folate receptor. Therefore, we focused to develop folate-based radiopharmaceutical that has the potential to be used as a therapeutic agent. We report here the synthesis and the radiolabeling of {sup 177}Lu-DOTA as well as the biodistribution data of our developed compound.

  4. Direct in vitro and in vivo comparison of {sup 161}Tb and {sup 177}Lu using a tumour-targeting folate conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Cristina; Reber, Josefine; Haller, Stephanie [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger; Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry, Bern (Switzerland); Bernhardt, Peter [The Sahlgrenska Academy, University of Gothenburg, Department of Radiation Physics, Gothenburg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengeneering, Gothenburg (Sweden); Zhernosekov, Konstantin [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2014-03-15

    The radiolanthanide {sup 161}Tb (T{sub 1/2} = 6.90 days, Eβ{sup -}{sub av} = 154 keV) was recently proposed as a potential alternative to {sup 177}Lu (T{sub 1/2} = 6.71 days, Eβ{sup -}{sub av} = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare {sup 161}Tb and {sup 177}Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09). {sup 161}Tb-cm09 and {sup 177}Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. In vivo {sup 161}Tb-cm09 and {sup 177}Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse models with regard to the biodistribution, the possibility for single photon emission computed tomography (SPECT) imaging and the antitumour efficacy. Potentially undesired side effects were monitored over 6 months by determination of plasma parameters and examination of kidney function with quantitative SPECT using {sup 99m}Tc-dimercaptosuccinic acid (DMSA). To obtain half-maximal inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower radioactivity concentration was required for {sup 161}Tb-cm09 (IC{sub 50} ∝0.014 MBq/ml and ∝2.53 MBq/ml) compared to {sup 177}Lu-cm09 (IC{sub 50} ∝0.063 MBq/ml and ∝4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies {sup 161}Tb-cm09 reduced tumour growth more efficiently than {sup 177}Lu-cm09. These findings were in line with the higher absorbed tumour dose for {sup 161}Tb-cm09 (3.3 Gy/MBq) compared to {sup 177}Lu-cm09 (2.4 Gy/MBq). None of the monitored parameters indicated signs of impaired kidney function over the whole time period of investigation after injection of the radiofolates. Compared to {sup 177}Lu-cm09 we demonstrated equal imaging

  5. Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model

    DEFF Research Database (Denmark)

    Eriksson, Sophie E; Elgström, Erika; Bäck, Tom

    2014-01-01

    for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later. METHODS: Rats bearing solid colon...... carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96....... Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. RESULTS: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with 211At-labeled antibodies did not reduce the proportion of animals developing metastases...

  6. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2012-09-01

    al., “The effects of induced hypogonadism on arterial stiffness , body composi- tion, and metabolic parameters in males with prostate cancer ,” The...Phase 2 Trial of 177Lu Radiolabeled Monoclonal Antibody J591in Patients with High-Risk Castrate Biochemically Relapsed Prostate Cancer PRINCIPAL...NUMBER in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer 5b. GRANT NUMBER W81XWH-09-1-0596 5c. PROGRAM ELEMENT NUMBER

  7. Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with {sup 177}Lu and evaluation in vitro and in vivo stability; Radiomarcado del peptido c-DOTA-RGD y c-DOTA-RGDf con {sup 177}Lu y evaluacion de su estabilidad in vitro e in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Vilchis J, A.

    2010-07-01

    Integrin {alpha}v{beta}3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the {alpha}v{beta}3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with {sup 177}Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of {sup 177}LuCl{sub 3} with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90{sup o} C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive {alpha}v{beta}3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. {sup 177}Lu-DOTA-RGD and {sup 177}Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to {open_square}{sub v}{open_square}{sub 3} receptors. (Author)

  8. 奥曲肽-葡聚糖-亲和素的偶联及其与177Lu-DTPA-BIS-BIOTIN的体外结合%177Lu-DTPA-BIS-BIOTIN Binding of Octreotide-dextran-avidinated PANC-1 Cell Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    邓新荣; 杜进; 翟士桢; 沈亦佳; 罗志福

    2011-01-01

    以葡聚糖为载体,奥曲肽为导向分子合成了生长抑素配体化合物奥曲肽-葡聚糖-亲和素(Tyr3-oct-reotide-dxtran 40-avidin,TOC-Dx40-Av);在体外模拟肿瘤预定位二步法以177Lu-DTPA-BIS-BIOTIN对TOC-Dx40-Av培养的PANC-1细胞的结合特性进行了研究.将长满人源胰腺癌细胞PANC-1的24孔板置于含有TOC-Dx40-Av的缓冲液中培养,2h后洗去上清液,再用含不同浓度177Lu- DTPA-BIS-BIOTIN(177Lu-DT-PA-BIS-BIOTIN的摩尔质量范围为48.8~391 pmol)的缓冲液继续培养细胞,使177Lu-DTPA-BIS-BIOTIN 与细胞上的亲和素结合,测定细胞上结合的放射性计数,考察TOC-Dx40-Av与177 Lu-DTPA-BIS-BIOTIN的结合特性以评价合成的大分子亲和素连接物的活性.实验结果显示,奥曲肽-葡聚糖-亲和素的化学纯度>99%,其中亲和素的含量为6.46 g/L.体外细胞结合实验结果表明,177Lu-DTPA-BIS-BIOTIN能快速与细胞上连接的亲和素结合,生物素与亲和素的摩尔比约为1∶1达到平衡.%Tyr3-octreotide, dextran-40 and avidin were used to prepare octreotide-dextran-avidin (TOC-Dx40-Av). DTPA-BIS-BIOTIN was labelled with 177Lu. The in vitro soma-tostatin receptor binding study was carried out by pretargeted method using TOC-Dx40-Av and 177Lu-DTPA-BIS-BIOTIN. The 24 well cell culture plates were prepared with PANC-1 cell monolayer and then incubated with TOC-Dx40-Av. After two washed with PBS, the cells were incubated with different concentration of 177 Lu-DTPA-BIS-BIOTIN (48. 8~ 391 pmol). Cells uptake was evaluated with y counter. The results showed that the chemi- cal purity of TOC-Dx40-Av was over 99%. The results also showed that TOC-Dx40-Av remained high receptor binding affinity to somatostatin receptor which indicated that TOC-Dx40-Av could bind to 177 Lu-DTPA-BIS-BIOTIN with the molar ratio of 1 ? 1 on the cell surface.

  9. {sup 177}Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity {sup 111}In-octreotide

    Energy Technology Data Exchange (ETDEWEB)

    Hubble, Daniel; Kong, Grace; Michael, Michael; Johnson, Val; Ramdave, Shakher; Hicks, Rodney John [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, East Melbourne, VIC (Australia)

    2010-10-15

    The aim of this retrospective study was to determine whether patients with previous peptide receptor radionuclide therapy using high-activity {sup 111}In-pentetreotide can be safely treated with {sup 177}Lu-octreotate and whether addition of radiosensitising chemotherapy increases the toxicity of this agent. Records of 27 patients (aged 17-75) who received 69 (median 3 per patient) {sup 177}Lu-octreotate administrations, including 29 in conjunction with radiosensitising infusional 5-fluorouracil (5-FU) (n = 27), or capecitabine (n = 2), between October 2005 and July 2007 subsequent to 1-8 prior cycles of {sup 111}In-pentetreotide therapy were analysed. Toxicity was assessed during and at 8-12 weeks post-treatment, with further long-term assessments including survival status reviewed till death or study close-out date of 1 November 2009. Reduction in blood counts was most marked following the first dose of {sup 177}Lu-octreotate but at early follow-up the only major haematological toxicity was a single case of grade 4 lymphopaenia. Both the presence of bone metastases and the administration of chemotherapy tended to result in greater reduction in blood counts, but these differences did not reach statistical significance. On long-term follow-up, 16 patients (59%) are alive with median overall survival of 36 months (32-44 months from first {sup 177}Lu-octreotate therapy). None of the recorded deaths was directly related to treatment toxicity. One patient had late grade 4 anaemia and thrombocytopaenia secondary to bone marrow failure from progressive infiltration by tumour. No other significant long-term haematological toxicities were recorded and no leukaemia was observed. No renal toxicity was observed on serial serum creatinine or radionuclide glomerular filtration rate (GFR) determination on initial or long-term follow-up. {sup 177}Lu-octreotate is a safe and well-tolerated therapy for patients who have previously been treated with {sup 111}In-pentetreotide and can

  10. {sup 177}Lu-EDTMP for palliation of pain from bone metastases in patients with prostate and breast cancer: a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Krishan Kant; Singla, Suhas; Arora, Geetanjali; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India)

    2015-01-15

    The purpose of this study was to evaluate the efficacy and safety of {sup 177}Lu-EDTMP for pain palliation in patients with bone metastases from castration-resistant prostate and breast cancer. The secondary objective was to compare low-dose and high-dose {sup 177}Lu-EDTMP in bone pain palliation. Included in the study were 44 patients with documented breast carcinoma (12 patients; age 47 ± 13 years) or castration-resistant prostate carcinoma (32 patients; age 66 ± 9 years) and skeletal metastases. Patients were randomized into two equal groups treated with {sup 177}Lu-EDTMP intravenously at a dose of 1,295 MBq (group A) or 2,590 MBq (group B). Pain palliation was evaluated using a visual analogue score (VAS), analgesic score (AS) and Karnofsky performance score (KPS) up to 16 weeks. Toxicity was assessed in terms of haematological and renal parameters. The overall response rate (in all 44 patients) was 86 %. Complete, partial and minimal responses were seen in 6 patients (13 %), 21 patients (48 %) and 11 patients (25 %), respectively. A favourable response was seen in 27 patients (84 %) with prostate cancer and in 11 patients (92 %) with breast cancer. There was a progressive decrease in the VAS from baseline up to 4 weeks (p < 0.05). Also, AS decreased significantly from 1.8 ± 0.7 to 1.2 ± 0.9 (p < 0.0001). There was an improvement in quality of life of the patients as reflected by an increase in mean KPS from 56 ± 5 to 75 ± 7 (p < 0.0001). The overall response rate in group A was 77 % compared to 95 % in group B (p = 0.188). There was a significant decrease in VAS and AS accompanied by an increase in KPS in both groups. Nonserious haematological toxicity (grade I/II) was observed in 15 patients (34 %) and serious toxicity (grade III/IV) occurred in 10 patients (23 %). There was no statistically significant difference in haematological toxicity between the groups. {sup 177}Lu-EDTMP was found to be a safe and effective radiopharmaceutical for bone pain

  11. Nanocrystalline zirconia: A novel sorbent for the preparation of {sup 188}W/{sup 188}Re generator

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarty, Rubel [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Shukla, Rakesh; Tyagi, A.K. [Chemistry Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Dash, Ashutosh [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai-400085 (India)], E-mail: adash@barc.gov.in; Venkatesh, Meera [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai-400085 (India)

    2010-02-15

    Nanocrystalline zirconia, a novel high capacity sorbent material was synthesized and tested for its utility in the preparation of {sup 188}W/{sup 188}Re generators. The structural investigation of the material was carried out using X-ray diffraction, surface area determination, FTIR and TEM micrograph analysis. Various experimental parameters were optimized to separate {sup 188}Re from {sup 188}W. The capacity of the material was found to be {approx}325 mg W/g at the optimum pH. A chromatographic {sup 188}W/{sup 188}Re generator was developed using this material from which >80% of {sup 188}Re generated could be eluted with 0.9% saline solution, with high radionuclidic, radiochemical and chemical purity and appreciably high radioactive concentration suitable for radiopharmaceutical applications.

  12. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, Giovanni; Sansovini, Maddalena; Ambrosetti, Alice; Severi, Stefano; Ianniello, Annarita; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola, FC (Italy); Monti, Manuela; Scarpi, Emanuela [IRST IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Donati, Caterina [IRST IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Amadori, Dino [IRST IRCCS, Department of Medical Oncology, Meldola (Italy)

    2014-10-15

    We evaluated the activity and safety profile of {sup 177}Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs). Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan registered completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8 GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve. Twenty-five (58 %) patients were treated with a ''standard'' Lu-PRRT full dosage (FD) of 25.7 GBq (range 22.2-27.8), while the remaining 18 patients (42 %) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4 GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7 %) cases and stable disease (SD) in 33 (77 %), with a disease control rate (DCR) of 84 %. Median response duration was 25 months (range 7-50). Median progression-free survival (PFS) was 36 months (95 % CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT. Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84 % DCR (95 % CI 73-95) that lasted for 25 months and a PFS of 36 months. Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity. (orig.)

  13. Automation of labelling of Lipiodol with high-activity generator-produced 188Re.

    Science.gov (United States)

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Boucher, Eveline; Raoul, Jean-Luc; Clément, Bruno; Garin, Etienne

    2011-02-01

    This work describes optimisation of the kit formulation for labelling of Lipiodol with high-activity generator-produced rhenium-188. Radiochemical purity (RCP) was 92.52±2.3% and extraction yield was 98.56±1.2%. The synthesis has been automated with a TADDEO module (Comecer) giving a mean final yield of 52.68±9.6%, and reducing radiation burden to the radiochemist by 80%. Radiolabelled Lipiodol ((188)Re-SSS/Lipiodol) is stable for at least 7 days (RCP=91.07±0.9%).

  14. Automation of labelling of Lipiodol with high-activity generator-produced {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Lepareur, Nicolas, E-mail: n.lepareur@rennes.fnclcc.f [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Ardisson, Valerie [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Noiret, Nicolas [Universite Europeenne de Bretagne, Rennes (France); Ecole Nationale Superieure de Chimie de Rennes, UMR CNRS 6226, Chimie Organique et Supramoleculaire, Avenue du General Leclerc, CS 50837, 35708 Rennes Cedex 7 (France); Boucher, Eveline; Raoul, Jean-Luc [INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Service d' Oncologie Digestive, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); Clement, Bruno [INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Garin, Etienne [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France)

    2011-02-15

    This work describes optimisation of the kit formulation for labelling of Lipiodol with high-activity generator-produced rhenium-188. Radiochemical purity (RCP) was 92.52{+-}2.3% and extraction yield was 98.56{+-}1.2%. The synthesis has been automated with a TADDEO module (Comecer) giving a mean final yield of 52.68{+-}9.6%, and reducing radiation burden to the radiochemist by 80%. Radiolabelled Lipiodol ({sup 188}Re-SSS/Lipiodol) is stable for at least 7 days (RCP=91.07{+-}0.9%).

  15. Design and optimization of the production process of radiopharmaceutical {sup 177}Lu-DOTA-Nal{sup 3}-Octreotide for the treatment of gastro-entero-pancreatic tumors; Diseno y optimizacion del proceso de produccion del radiofarmaco {sup 177}Lu-DOTA-Nal{sup 3}-Octreotido para el tratamiento de tumores gastroenteropancreaticos

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez G, M. F.

    2013-07-01

    The radiolabel peptides are molecules of interest in nuclear medicine for their therapeutic and diagnostic application in cancer. Among an impressing group of relevant peptides, those similar of the somatostatin, as the Nal{sup 3}-Octreotide (NOC), have established as potential radiopharmaceuticals when presenting significant affinity for the receptors of this peptide hormone that are over expressed and broadly distributed in tumors of neuroendocrine origin, as the gastro-entero-pancreatic tumors. On the other hand, the Lutetium-177 ({sup 177}Lu) is an ideal candidate for the peptides radiolabel and has favorable characteristics to be used in radionuclide therapy. The objective of this work was designing, optimizing and to document the production process of the radiopharmaceutical {sup 177}Lu-DOTA-Nal{sup 3}-Octreotide ({sup 177}Lu-DOTANOC) for the solicitude of its sanitary registration before the Comision Federal contra Riesgos Sanitarios (COFEPRIS). For the optimization of the production process a factorial design of three variables was evaluated with mixed levels (18 combinations), where the dependent variable is the radiochemical purity and the analytic method used to determine this parameter (High Performance Liquid Chromatography) was validated. Later on, by means of the production of 3 lots of the optimized formula of the radiopharmaceutical {sup 177}Lu-DOTANOC the production process was validated and the stability long term study to determine the period of useful life was carried out. The following pharmaceutical formulation was adopted as good: 1.85 GBq (0.5μg) of {sup 177}Lu, 250 μg of DOTANOC and 150 μL of acetates Buffer 1 M ph 5 in 5 m L of the medium. The analytic method used to determine the radiochemical purity of the formulation satisfied the requirements for the wished analytic application. We can conclude that the 3 validation lots prepared under protocols of Good Production Practices, in the Plant of Radiopharmaceuticals Production of the

  16. Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Melendez-Alafort, Laura [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)], E-mail: laura.melendez@unipd.it; Nadali, Anna; Zangoni, Elena [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy); Banzato, Alessandra; Rondina, Maria [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Rosato, Antonio [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Istituto Oncologico Veneto, IOV, Padova, Padua (Italy); Mazzi, Ulderico [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)

    2009-08-15

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of {sup 188}Re-HA was determined. Results: A stable complex of {sup 188}Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T{sub 1/2}{alpha}=21 min). Four hours after administration, {sup 188}Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47{+-}5.11% of the injected dose). The liver MTD in mice was {approx}40 Gy after 7.4 MBq of {sup 188}Re-HA injection. Conclusions: {sup 188}Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

  17. 188Re-labeled McAb 3H11 used as preventive for the peritoneal micrometasis of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    In advancing gastric cancer,especial1y when the serous is invaded,the p1antation of cancer cells in peritoneal is common and it affectspatients' survival time severe1y. Based on successfully labeledMcAb (monoclonal antibody) 3H11 with 188Re,we investigated the effect of RIT (Radioimmuno-Therapy) with188Re-3Hll on preventing the peritoneal micrometastasis ofgastric cancer cells in nude mice toincreasethe survival time. After 1×106 BGC-823 gastriccancer cel1s were injectedinto the peritoneal cavityof each mouse, 45BABL/C nude mice weredivided into 9groups. Each group receiveddifferent doses of 188Re-3Hll or188Re-IgG, or salineI.P.16 hours postoperation.The injected volume of each mouse was 1.0mL.The resultsshowed that the survival time depended on theinjected doses during 0 to 37 MBq.Thesurvival time was l70±25.3 dafter 37 MBq 188Re-3H11 were treated.It was over 5times more than that for the saline groupand about 3 times more than that for 37MBq188-Re IgG group (p<0.05).The mice hemogramwere reduced to lowest 14 days afterinjection,but they recovered after 28 d.Conclusion: with proper injection doses,early postoperative 188Re-3H11I.P. iseffective and safe for the prevention of intra-peritoneally injectedgastric cancer cells from surviving,growing and disseminating in nude mice.

  18. Multimodal Somatostatin Receptor Theranostics Using [64Cu]Cu-/[177Lu]Lu-DOTA-(Tyr3)octreotate and AN-238 in a Mouse Pheochromocytoma Model

    Science.gov (United States)

    Ullrich, Martin; Bergmann, Ralf; Peitzsch, Mirko; Zenker, Erik F.; Cartellieri, Marc; Bachmann, Michael; Ehrhart-Bornstein, Monika; Block, Norman L.; Schally, Andrew V.; Eisenhofer, Graeme; Bornstein, Stefan R.; Pietzsch, Jens; Ziegler, Christian G.

    2016-01-01

    Pheochromocytomas and extra-adrenal paragangliomas (PHEO/PGLs) are rare catecholamine-producing chromaffin cell tumors. For metastatic disease, no effective therapy is available. Overexpression of somatostatin type 2 receptors (SSTR2) in PHEO/PGLs promotes interest in applying therapies using somatostatin analogs linked to radionuclides and/or cytotoxic compounds, such as [177Lu]Lu-DOTA-(Tyr3)octreotate (DOTATATE) and AN-238. Systematic evaluation of such therapies for the treatment of PHEO/PGLs requires sophisticated animal models. In this study, the mouse pheochromocytoma (MPC)-mCherry allograft model showed high tumor densities of murine SSTR2 (mSSTR2) and high tumor uptake of [64Cu]Cu-DOTATATE. Using tumor sections, we assessed mSSTR2-specific binding of DOTATATE, AN-238, and somatostatin-14. Therapeutic studies showed substantial reduction of tumor growth and tumor-related renal monoamine excretion in tumor-bearing mice after treatment with [177Lu]Lu-DOTATATE compared to AN-238 and doxorubicin. Analyses did not show agonist-dependent receptor downregulation after single mSSTR2-targeting therapies. This study demonstrates that the MPC-mCherry model is a uniquely powerful tool for the preclinical evaluation of SSTR2-targeting theranostic applications in vivo. Our findings highlight the therapeutic potential of somatostatin analogs, especially of [177Lu]Lu-DOTATATE, for the treatment of metastatic PHEO/PGLs. Repeated treatment cycles, fractionated combinations of SSTR2-targeting radionuclide and cytotoxic therapies, and other adjuvant compounds addressing additional mechanisms may further enhance therapeutic outcome. PMID:27022413

  19. Peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin

    Energy Technology Data Exchange (ETDEWEB)

    Essen, Martijn van; Bakker, Willem H.; Kwekkeboom, Dik J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Aken, Maarten O. van [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2007-08-15

    Foregut carcinoid tumours have a different embryological origin than other gastroenteropancreatic neuroendocrine tumours (GEP NETs). In the total group of GEP NETs (n = 131), treatment with {sup 177}Lu-octreotate resulted in tumour remission in 47% of patients, with a median time to progression (TTP) of >36 months. As patients with foregut carcinoids may respond differently, we here present the effects of this treatment in a subgroup of patients with foregut carcinoids of bronchial, gastric or thymic origin. Nine patients with bronchial, five with gastric and two with thymic carcinoids were treated. All patients had metastasised disease. The intended cumulative dose of {sup 177}Lu-octreotate was 22.2-29.6 GBq. Southwest Oncology Group criteria were used for response evaluation. Bronchial carcinoids: Five patients had partial remission, one had minor response (MR, tumour size reduction: {>=}25%, <50%), two had stable disease (SD) and one had progressive disease (PD). Median TTP was 31 months. Gastric carcinoids: One patient had complete remission, one had MR and two had SD, including one with PD at baseline. One patient developed PD. Thymic carcinoids: One patient had SD. In the other patient, disease remained progressive. All patients: Overall remission rate was 50%, including MR. {sup 177}Lu-octreotate treatment can be effective in patients with bronchial and gastric carcinoids. Its role in thymic carcinoids cannot be determined yet because of the limited number of patients. The overall remission rate of 50% in patients with the studied foregut carcinoids is comparable to that in the total group of GEP NETs. (orig.)

  20. The efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong-Jang; Pak, Kyoungjune [Pusan National University Hospital, Department of Nuclear Medicine and Biomedical Research Institute, Busan (Korea, Republic of); Koo, Phillip J.; Kwak, Jennifer J.; Chang, Samuel [University of Colorado School of Medicine, Department of Radiology, Aurora, CO (United States)

    2015-12-15

    This study was performed to evaluate the efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of ''neuroendocrine'', ''{sup 177}Lu'' and ''prognosis''. All published studies of neuroendocrine tumours treated with {sup 177}Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8 % with a pooled effect of 29 % [95 % confidence interval (CI) 24-34 %]. Disease control rates ranged from 71.8 to 100 %. The random-effects model showed an average disease control rate of 81 % (95 % CI 71-91 %). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5 % with a pooled effect of 23 % (95 % CI 11-38 %). Disease control rates ranged from 73.9 to 89.1 %. The random-effects model showed an average disease control rate of 82 % (95 % CI 71-91 %). {sup 177}Lu-labelled PRRT is an effective treatment

  1. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Wu, Yin; Pfeifer, Andreas Klaus; Myschetzky, Rebecca;

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising...... clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following...

  2. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2014-09-01

    ates such as choline, citric acid , and certain lipids that are powerful biomarkers for aggressive disease. More recently, with support from the PCRP...flow-cytometry. Glial-derived MP (GFAP+) were measured using anti-glial fibrillary acidic protein (GFAP)-FITC and TF-bearing (TF+ MP) using anti-CD142...fractionated doses of 177Lu-J591 (initial dose 20 mCi/m2 x2 up to max of 40 mCi/m2 x2) with cycle 3. Cycle 4 of docetaxel was planned 6 weeks after

  3. A review on the current status and production technology for {sup 188}W-{sup 188}Re generator system

    Energy Technology Data Exchange (ETDEWEB)

    Kuznetsov, R. A.; Han, H. S.; Cho, W. K.; Park, U. J.; Kim, Y. M

    1998-11-01

    The current status of {sup 188}W-{sup 188}Re generator production technology were reviewed in PART 1. Main interests were given to the aspects of {sup 188}W reactor production, irradiated targets reprocessing and generator loading technologies, such as alumina type and gel type generators. In order to develop the more convenient and advanced {sup 188}W-{sup 188}Re generator, further studies must be carried out to get the precise evaluation of production and burn-up cross section of {sup 188}W, the more easily realizable generator loading procedure, and also to optimize the column and generator design to compensate the deterioration of generator performance because of parent radionuclide decay. By irradiation of {sup 186}W enriched sample, {sup 188}W-{sup 188}Re generator production experiments were performed to evaluate the possibility of {sup 188}W-{sup 188}Re generator production using HANARO, and PART 2 describes about the experiments. The experimental results shows the possibility of practical {sup 188}W-{sup 188}Re generator production using of low-specific activity {sup 188}W produced in HANARO. (author). 79 refs., 4 tabs., 26 figs.

  4. 188Re(V)-DMSA revisited: preparation and biodistribution of a potential radiotherapeutic agent with low kidney uptake.

    Science.gov (United States)

    Dadachova, E; Chapman, J

    1998-02-01

    Methods of preparation and biodistribution in mice of tin-free 99Tcm(V)-DMSA and 188Re(V)-DMSA, a potential matching pair of radiopharmaceuticals for diagnosis and therapy of certain cancers, are described. Preparation of tin-free 188Re(V)-DMSA (I) is based on reduction with either SO2-releasing compounds like Na2S2O4 (30 mg Na2S2O4, 10 mg DMSA, 1 mg L-ascorbic acid, 37 degrees C, 60 min incubation), Na2S2O5 (as before, 70 degrees C, 15 min incubation), or HBr (0.2 ml 48% HBr, 0.2 ml 7 M HCl, 10 mg DMSA, 1 mg L-ascorbic acid, 70 degrees C, 60 min incubation). I exhibits significantly lower kidney uptake than tin-containing 188Re(V)-DMSA (II) (2-3% and 49% injected dose per gram organ, 1 h post-injection, respectively). HPLC profiles of I and II are similar. DMSA excess in tin-free 188Re(V)-DMSA is not responsible for the low kidney uptake of I. High kidney uptake of II is explained by formation of a mixed 188Re(V)-Sn-DMSA complex in vivo. Age-linked bone uptake in mice dependent on the maturation of the bone is demonstrated for both I and II.

  5. Lipiodol solution of a lipophilic agent, {sup 188}Re-TDD, for the treatment of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min E-mail: jmjng@snu.ac.kr; Kim, Young Joo; Lee, Yoon Sang; Ko, Jun Il; Son, Miwon; Lee, Dong Soo; Chung, June-Key; Park, Jae Hyung; Lee, Myung Chul

    2001-02-01

    Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of {sup 188}Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of {sup 188}Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of {sup 188}Re-TDD is a promising agent for liver cancer therapy.

  6. β-IRRADIATION WITH A LIQUID 188Re-FILLED BALLOON PREVENTS NEOINTIMAL PROLIFERATION IN THE CAROTID OF RABBIT

    Institute of Scientific and Technical Information of China (English)

    朱建国; 崔长琮; 崔翰斌; 胡国英; 马爱群; 王东琦; 付文

    2002-01-01

    Objective To evaluate the role of β-irradiatio n with a liquid 188Re-filled balloon for limiting neointimal prolifer ation. Methods Balloon-overstretched injury was performed in the rabb it carotid artery, then β-irradiation using the liquid 188Re-filled balloon was followed immediately, and the prescribed doses was 0, 15Gy or 20Gy a t 0.5mm from the surface of vessel. All animals survived and were sacrificed at three weeks. Histopathologic analysis was performed. Results In the control group, the neointimal area was larger ( 0.40±0.04)mm2, as compared with (0.23±0.06)mm2 of the 15Gy irradiated g roup and (0.15±0.02)mm2 in the 20Gy group (P<0.05). Conclusion The β-irradiation with a liquid 188Re-f illed balloon is safe and effective.

  7. Synthesis and application of {sup 188}Re-MN-16ET/Lipiodol in a hepatocellular carcinoma animal model

    Energy Technology Data Exchange (ETDEWEB)

    Tang, I-Chang [Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China); Luo, Tsai-Yueh, E-mail: tylo@iner.gov.tw [Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China); Liu, Show-Wen [Chemistry Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China); Chan, Sun-Ho [Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 40705 (China); Kung, Hong-Chang [Department of Electronic Engineering, Tung Nan University, Taipei, Taiwan 22202 (China); Peng, Cheng-Liang [Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China); Lin, Wan-Yu; Chang, Yu [Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 40705 (China); Lin, Wuu-Jyh [Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China)

    2011-10-15

    Introduction: Hepatocellular carcinoma is the most common form of primary hepatic carcinoma. A new N{sub 2}S{sub 2} tetradentate ligand, N-[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3- [2-(triphenylmethyl)thioethyl]octadecanoate (H{sub 3}MN-16ET), was introduced and labeled with {sup 188}Re to create {sup 188}Re-MN-16ET in the Lipiodol phase. The potential of {sup 188}Re-MN-16ET/Lipiodol for hepatoma therapy was evaluated in a hepatocellular carcinoma animal model of Sprague-Dawley rats implanted with the N1S1 cell line. Methods: Synthesis of H{sub 3}MN-16ET was described, and characterization was identified by infrared, nuclear magnetic resonance and mass spectra. We compared the effects of transchelating agents (glucoheptonate or tartaric acid) and a reducing agent (stannous chloride) on the complexing of {sup 188}Re-perrhenate and H{sub 3}MN-16ET. Twenty-four rats implanted with hepatoma were injected with 3.7 MBq/0.1 ml of {sup 188}Re-MN-16ET/Lipiodol or {sup 188}Re-MN-16ET via transcatheter arterial embolization. Biodistribution experiments and single-photon emission computed tomography imaging were performed to investigate tumor accumulation. Results: H{sub 3}MN-16ET was proved to easily conjugate with the Re isotope and showed good solubility in Lipiodol. The radiochemical purity of {sup 188}Re-MN-16ET/Lipiodol with 10 mg tartaric acid and stannous chloride was shown to be more than 90%. The major distribution sites of {sup 188}Re-MN-16ET in Sprague-Dawley rats were hepatoma and the liver. However, the radioactivity at the tumor site postadministered with {sup 188}Re-MN-16ET was quickly decreased from 9.15{+-}0.23 (at 1 h) to 2.71%{+-}0.18% of injected dose/g (at 48 h). The biodistribution and micro-single-photon emission computed tomography/computed tomography image data showed that {sup 188}Re-MN-16ET/Lipiodol was selectively retained at the tumor site, with 11.55{+-}1.44, 13.16{+-}1.46 and 10.67%{+-}0.95% of injected dose/g at 1, 24 and 48 h

  8. Evaluating the potential of {sup 188}Re-SOCTA-trastuzumab as a new radioimmunoagent for breast cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Luo, T.-Y. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China)], E-mail: tylo@iner.gov.tw; Tang, I-C.; Wu, Y.-L.; Hsu, K.-L. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China); Liu, S.-W. [Chemistry Division, Institute of Nuclear Energy Research, Taoyuan 325, Taiwan (China); Kung, H.-C. [Department of Electrical Engineering, Tung Nan University, Taipei 222, Taiwan (China); Lai, P.-S. [Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan (China); Lin, W.-J. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China)

    2009-01-15

    Introduction: Radioimmunotherapy, which utilizes monoclonal antibodies and therapeutic radioisotopes against antigen-expressing tumor tissues, is an attractive therapeutic approach for cancer therapy. Trastuzumab (Herceptin) is a humanized anti-HER-2/neu monoclonal antibody for breast cancer treatment. In this paper, we introduce a new radioimmunoagent, {sup 188}Re-trastuzumab, via a bifunctional ligand, succinimidyl 3,6-diaza-5-oxo-3-[2-((triphenylmethyl)thio)ethyl] -8-[(triphenylmethyl)thio]octanoate (SOCTA), and evaluate its potential to be a therapeutic radiopharmaceutical for breast cancer treatment. Methods: Equimolar amounts of SOCTA and trastuzumab were selected to react, and the conjugation ratio of SOCTA-trastuzumab was evaluated by the MALDI-TOF method. The immunoreactivity of SOCTA-trastuzumab was compared with nonconjugated trastuzumab in HER-2/neu overexpressing human breast cancer cell BT-474. Biodistribution experiment and microSPECT/CT images of {sup 188}Re-SOCTA-trastuzumab being administered intravenously to SCID mice bearing xenografted BT-474 breast cancer were investigated to evaluate the tumor-targeting capability. Results: The covalent attachment of SOCTA to trastuzumab (at 1:1 molar ratio) resulted in the averaged conjugation ratio of 0.27{+-}0.06 (n=3). The complex could easily be labeled with {sup 188}Re and achieve 95% radiochemical purity (RCP) after 1 h of reaction at room temperature. The in vitro stability study also revealed that the RCP of {sup 188}Re-SOCTA-trastuzumab was at a value of more than 85% after 48 h of incubation with human serum. The immunoreactivity evaluation showed that SOCTA-trastuzumab and nonconjugated trastuzumab had similar binding capacity (B{sub max}) to HER-2/neu receptor in BT-474 cells. The animal experiments showed that {sup 188}Re-SOCTA-trastuzumab accumulated more intensively in the tumor site as compared to normal tissue. Conclusion: We suggest that {sup 188}Re-SOCTA-trastuzumab could be a potential

  9. Comparative study of 188Re( V )-DMSA and 99mTc ( V )-DMSA in tumor model%188Re(V)-DMSA与99mTc(V)-DMSA在肿瘤模型体内的对比研究

    Institute of Scientific and Technical Information of China (English)

    孙逊; 安锐

    2004-01-01

    Objective To compare the biodistribution and imaging characteristics of 188Re(V)-DMSA and 99mTc(V)-DMSA in tumor model, and to discuss the possibility of treating tumors with 188Re(V)-DMSA. Methods The solid neoplasm bearing mice (Ehrlich carcinoma bearing mice) models underwent biodistribution study and static whole body planar imaging after injection of 188Re(V)-DMSA and 99mTc(V)-DMSA respectively. When the mice were sacrificed at different time after the injection, the tumor, blood and contralateral normai muscles were removed, weighted and the radioactivity was measured. Then the radioactivity ratios of target (tumor)-to-blood (T/B),target-to-non targeted (contralateral limbs or muscles) (T/NT) were calculated. ROIs were drawn and T/NT were calculated in planar imagines. Results Two radiopharmaceuticals were mainly concentrated in bone and kidney, and the uptake ratios in tumor were high too.The half-clearance times of these two radiopharmaceuticals in blood were both less than 1h. The greatest T/NT ratio of 99mTc group was higher than 188Re group in planar imagings, but the highest T/B, T/NT ratios of these two radiopharmaceuticals in biodistribution study had no significant difference and were all above 3.0. Conclusion The biodistribution characteristics of 188Re(V)-DMSA and 99mTc( V)-DMSA were similar. 188Re(V)-DMSA has good applied foreground in treating tumors and their metastases.%目的比较188Re(V)-DMSA(五价188Re-二巯基丁二酸钠)和99mTc(V)-DMSA在肿瘤模型体内生物分布与显像的特点,探讨188Re(V)-DMSA用于肿瘤治疗的可能性.方法用188Re(V)-DMSA和99mTc(V)-DMSA对实验性实体肿瘤(小鼠艾氏腹水癌)模型进行生物学分布实验和全身平面显像,并通过脏器克组织百分摄取率(%ID/g)测定法和感兴趣区(ROI)技术进行定量分析,计算各时点两种放射性药物的靶/血、靶/非靶比值.结果两种放射性药物均主要浓聚于骨骼和肾脏,肿瘤组织也有较高的摄

  10. Development of {sup 177}Lu-DTPA-SPIO conjugates for potential use as a dual contrast SPECT/MRI imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Shanehsazzadeh, Saeed; Yousefnia, Hassan [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Gruettner, Cordula [Micromod Partikeltechnologie GmbH, Rostock (Germany); and others

    2016-08-01

    This study describes the preparation, biodistribution of {sup 177}Lu-DTPA-SPIO after intravenous injection in rats. The chelator DTPA dianhydride was conjugated to SPIO NPs using a small modification of the well-known cyclic anhydride method. Conjugation was done at a 1:2 (SPIO:ccDTPA) molar ratio. Conjugation reaction was purified with Magnetic assorting column (MACs) using high gradient magnetic field following incubation, the radio labeled conjugate was checked using RTLC method for labeling and purity checked. The RTLC showed that labeling yield was above 99% after purification and the compound have good in-vitro stabilities until 48 h post injection in the presence of human serum. The biodistribution of {sup 177}Lu-DTPA-SPIO in rats showed dramatic uptake in the reticuloendothelial system (RES) and their clearance is so fast in other organs especially in the blood. In conclusion, due to high uptakes of this radiotracer in the liver and spleen and their fast clearance from other tissues, especially in blood, it is suggested that this radiotracer would be suitable for RES studies.

  11. Individualized dosimetry in patients undergoing therapy with {sup 177}Lu-DOTA-D-Phe{sup 1}-Tyr{sup 3}-octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Sandstroem, Mattias [Uppsala University Hospital, Department of Oncology, Radiology and Clinical Immunology, Division of Medical Physics, Uppsala (Sweden); Uppsala University Hospital, Department of Hospital Physics, Uppsala (Sweden); Garske, Ulrike [Uppsala University Hospital, Department of Medical Sciences, Division of Nuclear Medicine, Uppsala (Sweden); Granberg, Dan [Uppsala University Hospital, Department of Medical Sciences, Division of Endocrine Oncology, Uppsala (Sweden); Sundin, Anders [Karolinska University Hospital, Department of Molecular Medicine and Surgery, Division of Diagnostic Radiology, Stockholm (Sweden); Lundqvist, Hans [Uppsala University, Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala (Sweden)

    2010-02-15

    In recent years, targeted radionuclide therapy with [{sup 177}Lu-DOTA{sup 0}, Tyr{sup 3}]octreotate for neuroendocrine tumours has yielded promising results. This therapy may be further improved by using individualized dosimetry allowing optimization of the absorbed dose to the tumours and the normal organs. The aim of this study was to investigate the feasibility and reliability of individualized dosimetry based on SPECT in comparison to conventional planar imaging. Attenuation-corrected SPECT data were analysed both by using organ-based volumes of interest (VOIs) to obtain the total radioactivity in the organ, and by using small VOIs to measure the tissue radioactivity concentration. During the first treatment session in 24 patients, imaging was performed 1, 24, 96 and 168 h after [{sup 177}Lu-DOTA{sup 0}, Tyr{sup 3}]octreotate infusion. Absorbed doses in non tumour-affected kidney, liver and spleen were calculated and compared for all three methods (planar imaging, SPECT organ VOIs, SPECT small VOIs). Planar and SPECT dosimetry were comparable in areas free of tumours, but due to overlap the planar dosimetry highly overestimated the absorbed dose in organs with tumours. Furthermore, SPECT dosimetry based on small VOIs proved to be more reliable than whole-organ dosimetry. We conclude that SPECT dosimetry based on small VOIs is feasible and more accurate than conventional planar dosimetry, and thus may contribute towards optimising targeted radionuclide therapy. (orig.)

  12. Synthesis, analysis, purification and biodistribution in an animal model of radiopharmaceutical {sup 177}Lu{sup 3+} -dotatato for diagnostic and therapeutic use in neuroendocrine tumors; Sintese, analise, purificacao e biodistribuicao em modelo animal do radiofarmaco {sup 177}Lu{sup 3+} -dotatato para uso diagnostico e terapeutico em tumores neuroendocrinos

    Energy Technology Data Exchange (ETDEWEB)

    Caldeira Filho, Jose de Souza

    2009-07-01

    The aim of this work was to propose rationalization in the synthesis, analysis and purification of radiopharmaceutical {sup 177} Lu{sup 3+} - DOTATATO for diagnostic and therapeutic use in neuroendocrine tumors, as well as for evaluation g biodistribution of this radiopharmaceutical an animal-mode. The complexation reaction for the synthesis of radiopharmaceutical was carried out in ammonium acetate buffer 0.5 M, p H 7.0, for 30 minutes at 95 deg C. The radiochemical purity was > 95%, according to analysis by chromatography in ITLC-SG, when using the sodium citrate buffer 0,1 M, p H 5.0, as the mobile phase. The molar-limit ratio {sup 177}Lu{sup 3+}:DOTATATO, in ammonium acetate buffer 0.5 M, p H 7.0, for 30 minutes at 95 deg C, was dependent on the specific activity and origin of the radioisotope, this being 1:3.5 (370 MBq : 26{mu}g) for that from the Oak Ridge National Laboratory /USA, and 1:16 (370 MBq: 11.8 {mu}g) for that from Nuclear Analytical and Medical Services/Holland, when considering a decay of five days from the production date of te radioisotopes. This rationalization in the synthesis of radiopharmaceutical {sup 177}Lu{sup 3+} - DOTATATO permits high economy in production costs. Chemical studies on the synthesis of radiopharmaceuticals also placed in evidence the interference of {sup 177}Hf{sup 4+}, the decay product of {sup 177}Lu{sup 3=}, as the {sup 177} Lu{sup 3=} competitor for DOTATATO. Radiopharmaceutical preparation proved to be stable during 24 hours, at an activity rate of 2775 MBq, with the addition of 0.6 mg/mL of gentisic acid and when kept in dry ice. In biodistribution studies on Swiss and Nuce mice, the specificity of radiopharmaceutical for somatostatin positive-receptor tissues, such as the pancreas, stomach, lungs, adrenal glands, kidneys and the cell tumor AR42J was demonstrated. (author)

  13. Synthesis and evaluation of Lys{sup 1}(α, γ-Folate)Lys{sup 3}({sup 177}Lu-DOTA)-Bombesin(1-14) as a potential theranostic radiopharmaceutical for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aranda L, L.; Ferro F, G.; Azorin V, E.; Ramirez, F. M.; Ocampo G, B.; Santos C, C.; Jimenez M, N. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Issac O, K. [Universidad Autonoma del Estado de Mexico, Facultad de Medicina, 50180 Toluca, Estado de Mexico (Mexico)

    2015-10-15

    Full text: Lutetium-177 labeled hetero bivalent molecules that interact with different targets on tumor cells have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this work was to synthesize Lys{sup 1} (α,γ-Folate)-Lys{sup 3}({sup 177}Lu-DOTA)-Bombesin (1-14) ({sup 177}LuFolate-Bn), as well as to assess its in vitro and in vivo potential for molecular imaging and targeted radiotherapy of breast tumors expressing folate receptors (Fr) and gastrin releasing peptide receptors (GRPR). Lys{sup 1} Lys{sup 3} (DOTA)-Bombesin (1-14) was conjugated to the terminal carboxylic group of the folic acid and the product purified by size-exclusion HPLC. Chemical characterization was carried out by UV-vis, Ft-IR spectroscopies and MALDI-TOF mass spectrometry. {sup 177}Lu labeling was performed by reaction of {sup 177}LuCl{sub 3} with the Lys{sup 1} (α,γ-Folate)-Lys{sup 3} (DOTA)-Bombesin (Folate-Bn) conjugate. In vitro binding studies were carried out in T47D breast cancer cells (positive to Fr and GRPR). Biokinetic studies and micro-SPECT/CT images were obtained using athymic mice with T47D induced tumors. Spectroscopic studies and HPLC analyses indicated that the conjugate was obtained with high chemical and radiochemical purity (98 ± 1.3%). T47D-tumors were clearly visible with high contrast at 2 h after radiopharmaceutical administration. The {sup 177}Lu-absorbed dose delivered to tumors was 23.9 ± 2.1 Gy (74 MBq, intravenously administered) {sup 177}Lu-Folate-Bn demonstrated properties suitable as a theranostic radiopharmaceutical for breast tumors expressing Fr s and GRPR s. (Author)

  14. {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Sahoo, Ranjit Kumar [All India Institute of Medical Sciences, Department of Medical Oncology, BR Ambedkar Rotary Cancer Hospital, New Delhi (India); Seth, Amlesh [All India Institute of Medical Sciences, Department of Urology, New Delhi (India)

    2017-01-15

    The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic{sup 68}Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly {sup 177}Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and toxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity

  15. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    Directory of Open Access Journals (Sweden)

    Michael Bzorek

    2013-10-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.

  16. Efficiency of the metabolic radiotherapy with {sup 177}Lu Octreotate in the case of gastric endocrine tumor with hepatic metastases; Efficacite de la radiotherapie metabolique au{sup 177}Lu Octreotate dans le cas d'une tumeur endocrine gastrique avec metastases hepatiques

    Energy Technology Data Exchange (ETDEWEB)

    Leghzali Moise, H.; Besse, H.; Stievenart, J.L [Medecine nucleaire, hopital Beaujon, AP-HP, (France); Scigliano, S. [service hospitalier Frederic-Joliot, Orsay, (France); Mortazavi Jehannod, N.; Lebtahid, R.; Le Guludec, D. [medecine nucleaire, hopital Bichat, AP-HP, (France); Ruszniewski, P. [pancreato-gastroenterologie, hopital Beaujon, AP-HP, (France)

    2009-05-15

    The therapy means of evolved, metastases or inoperable forms of digestive endocrine tumors are limited. we illustrate a case of treatment efficiency by {sup 177}Lu-Octreotate of a well differentiated gastric endocrine tumor with hepatic metastases. conclusions: the metabolic radiotherapy of endocrine tumors constitute a new alternative of conventional treatments, showing the achievement of objective tumor responses at advanced stages, and in failure of conventional treatments. it is necessary to identify the predictive factors of the therapy response in order to optimize the results and to limit the toxicity. (N.C.)

  17. Evaluation of the cell death mechanisms activated by the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy; Evaluacion de los mecanismos de muerte celular activados por el radiofarmaco {sup 177}Lu-DOTA-anti-CD20 en un intervalo de dosis de 1 a 5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G., E-mail: erica.azorin@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2016-10-15

    The radio immunotherapy with anti-CD20 antibodies significantly increases the remission rate of patients with B-cell lymphomas over expressing the CD20. The radiolabeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. The anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum reach on soft tissue of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45 m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of action by synergistic effect of anti-CD20 and radionuclide have not been studied. In this work was evaluated; by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-Anti-CD20 in non-Hodgkin (Raji) lymphoma cells. The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20, are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation, activation of repair mechanisms and increased radio sensitivity) causes the acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation

  18. In vitro and in vivo studies in Balb-c and nude mice of a new {sup 177}Lu-Bombesin analog developed for prostate tumor diagnosis and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Pujatti, Priscilla B.; Santos, Josefina S.; Couto, Renata M.; Araujo, Elaine B. de; Mengatti, Jair [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia], e-mail: priscillapujatti@yahoo.com.br; Suzuki, Miriam F. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia

    2009-07-01

    In this work we describe the radiolabeling with {sup 177}Lu and some properties of the novel bombesin analog BBNp6 - DOTA-X-BBN(6-14), where X is a spacer of six aminoacids. Bombesin (BBN) is an analog of human gastrin releasing peptide (GRP) isolated from the skin of the frog Bombina bombina in 1970. Development of radiolabeled BBN derivatives as agents for diagnostic imaging and systemic radiotherapy has increased considerable because of the observation that GRP receptors (GRPr) are over-expressed in a variety of human tumor cells, such as prostate tumor cells. {sup 177}Lu-labeled peptides are attractive due to the excellent radiophysical properties and commercial availability of the radiometal. BBNp6 was labeled with high yield after reacting with 92.5 MBq of {sup 177}LuCl3 at 90 deg C for 30 minutes and this mixture kept stable for more than 96 hours at 4 deg C and 1 hour in human plasma. In vivo studies showed a multicompartimental distribution model with fast blood clearance, mainly performed by renal pathway. In addition, {sup 177}Lu-BBNp6 showed high affinity for PC-3 tumor xenografts, but not for pancreas and intestine (GRP positive tissues), suggesting its specificity and usefulness for prostate tumor treatment. Moreover, scintigraphic images showed that this derivative can also be a tool in this tumor diagnosis. So, BBNp6 is a promising radiopharmaceutical for prostate tumor imaging and treatment. (author)

  19. Development of methods of labeling pentavalent DMSA with {sup 99m}Tc and {sup 188}Re; Desenvolvimento de metodos para marcacao de DMSA pentavalente com {sup 99m}Tc e {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Brambilla, Tania de Paula, email: jtoniolo@ipen.br

    2009-07-01

    Technetium-99 m is the most useful radionuclide in diagnostic imaging procedures in Nuclear Medicine, more than 80 percent of radiopharmaceuticals are {sup 99m}Tc-labeled compounds. {sup 99m}Tc-DMSA(V) has been used for imaging of soft tissue, head and neck tumors. It shows a particularly high specificity for medullary thyroid carcinoma and bone metastases in a variety of cancers. Biodistribution studies of {sup 188}Re-DMSA(V) have shown that its general pharmacokinetic properties are similar to that of {sup 99m}Tc-DMSA(V), so this agent could be used for targeted radiotherapy of these tumors. The aim of this work is the development of methods of labeling DMSA(V) with {sup 99m}Tc and {sup 188}Re. {sup 99m}Tc-DMSA(V) can be prepared by two methods. One of them is the indirect one, through the use of a commercial kit of DMSA (III), by adjusting the pH from 2.5 to {approx} 8.5 with NaHCO{sub 3}. This method was evaluated and optimized presenting high labeling yields. The other method is the direct one, through the preparation of a lyophilised kit ready for labeling with {sup 99m}Tc, being the method of interest of this work, due to the easy of its clinical use. The most adequate formulation of the kit was: 1.71 mg of DMSA, 0.53 mg of SnCl{sub 2}.2H{sub 2}O and 0.83 mg of ascorbic acid (pH 9). Labeling yields higher than 95% were achieved labeling this kit with 1 to 2 m L of {sup 99m}Tc with activities up to 4736 MBq (128 mCi). The kit was stable up to 6 months and biodistribution studies confirmed the quality of the DMSA (V) labeled with {sup 99m}Tc using this kit. The reduction potential of Re is lower than the one for Tc, so the labeling conditions of {sup 188}Re-DMSA(V) are different from the ones used for {sup 99m}Tc- DMSA(V). {sup 188}Re-DMSA(V) is prepared in acid solution, that makes it possible to use the DMSA (III) commercial kit developed for labeling with {sup 99m}Tc, prepared in pH 2.5, for labeling with {sup 188}Re. Labeling yields higher than 95% were

  20. Uptake of the {sup 188}Re(V)-DMSA complex by cervical carcinoma cells in nude mice: pharmacokinetics and dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Salinas, Laura; Ferro-Flores, Guillermina E-mail: gff@nuclear.inin.mxtendilla@acnet.net; Arteaga-Murphy, Consuelo; Pedraza-Lopez, Martha; Hernandez-Gutierrez, Salomon; Azorin-Nieto, Juan

    2001-03-01

    The uptake of the rhenium-188 ({sup 188}Re(V)-DMSA) complex of dimercaptosuccinic acid by cervical carcinoma cells in nude mice was evaluated. The pharmacokinetics and dosimetry calculations in normal rats were also evaluated. The images obtained in mice did not show significant accumulation in metabolic organs and the biodistribution studies showed that 3.52{+-}0.76% of the injected activity per gram (n=4) was taken up by the tumor. This percentage produces a cumulated activity of 35.63{+-}8.40 MBq h and an equivalent dose per injected activity of 260{+-}8.91 mSv/MBq. Pharmacokinetics and dosimetry of the {sup 188}Re(V)-DMSA complex indicate that this radiopharmaceutical could be evaluated in patients with soft tissue tumors, since the risk of radiation damage to the kidney or red bone marrow could not be an obstacle for its application in therapeutic nuclear medicine.

  1. Radiolabeling of rituximab with {sup 188}Re and {sup 99m}Tc using the tricarbonyl technology

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Jeger, Simone [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Osso, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Schibli, Roger, E-mail: roger.schibli@psi.c [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)

    2011-01-15

    Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20{sup +} B-cell tumors. Rituximab radiolabeled with {beta}{sup -} emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the {sup 99m}Tc- and {sup 188}Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX{sub wt}) as well as a reduced form (RTX{sub red}) was labeled with {sup 99m}Tc/{sup 188}Re(CO){sub 3}. The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX{sub red} were superior to that of RTX{sub wt} ({sup 99m}Tc: 98% after 3 h for RTX{sub red} vs. 70% after 24 h for RTX{sub wt}). {sup 99m}Tc(CO){sub 3}-RTX{sub red} was used without purification for in vitro and in vivo studies whereas {sup 188}Re(CO){sub 3}-RTX{sub red} was purified to eliminate free {sup 188}Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37{sup o}C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of {sup 99m}Tc(CO){sub 3}-RTX{sub red} but not with pre-purified {sup 188}Re(CO){sub 3}-RTX{sub red}. Both conjugates revealed high binding affinity to the CD20 antigen (K{sub d}=5-6 nM). Tumor uptake of {sup 188}Re(CO){sub 3}-RTX{sub red} was 2.5 %ID/g and 0.8 %ID/g for {sup 99m}Tc(CO){sub 3}-RTX{sub red} 48 h after injection. The values for other

  2. Reduction of β-radiation exposure during preparation of 188Re-labelled Lipiodol for hepatocellular carcinoma treatment.

    Science.gov (United States)

    Lepareur, Nicolas; Laffont, Sophie; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-02-01

    Rhenium-188 (188Re) is of widespread interest for treating various diseases because of its attractive physical and chemical properties. The routine preparation of therapeutic doses of 188Re-labelled tracers can result in significant radiation exposure to the operator. We studied the impact of automating the preparation of 188Re-Lipiodol on the radiochemist's exposure, as well as the importance of the model of syringe shielding. To monitor radiation exposure continuously readable electronic personal dosimeters were used. Thermoluminescence dosimeters were fixed to the probable most exposed fingers of the radiochemist during preparation of the radiotracer and during the syringing. Dose rates were measured using a Babyline. Automation of the synthesis reduced personal dose equivalents from 2.60±4.35 to 1.61±1.20 µSv/GBq [Hp(10)] and from 38.37±55.28 to 21.84±16.14 µSv/GBq [Hp(0.07)]. Dose to the extremities was also reduced (-80% for the right hand; -58% for the left one). The Lemer-Pax PSWG syringe shield led to a slightly lower dose to the hands compared with the Medisystem (1.1±0.27 vs. 1.34±0.6 mSv/GBq for the right finger). Automation of the synthesis leads to a significant decrease in radiation exposure to the operator. The Lemer-Pax PSWG syringe shield provides better hand protection than the smaller Medisystem Mediclic.

  3. Rhenium-188 Production in Hospitals, by W-188/Re-188 Generator, for Easy Use in Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Maria Argyrou

    2013-01-01

    Full Text Available Rhenium-188 (Re-188 is a high energy -emitting radioisotope obtained from the tungsten-188/rhenium-188 (W-188/Re-188 generator, which has shown utility for a variety of therapeutic applications in nuclear medicine, oncology, and interventional radiology/cardiology. Re-188 decay is accompanied by a 155 keV predominant energy -emission, which could be detected by -cameras, for imaging, biodistribution, or absorbed radiation dose studies. Its attractive physical properties and its potential low cost associated with a long-lived parent make it an interesting option for clinical use. The setup and daily use of W-188/Re-188 generator in hospital nuclear medicine departments are discussed in detail. The clinical efficacy, for several therapeutic applications, of a variety of Re-188-labeled agents is demonstrated. The high energy of the -emission of Re-188 is particularly well suited for effective penetration in solid tumours. Its total radiation dose delivered to tissues is comparable to other radionuclides used in therapy. Furthermore, radiation safety and shielding requirements are an important subject of matter. In the case of bone metastases treatment, therapeutic ratios are presented in order to describe the efficacy of Re-188 usage.

  4. Prediction of the correct measured activity of {sup 186}Re and {sup 188}Re from reactor produced natural rhenium using an artificial neural network

    Energy Technology Data Exchange (ETDEWEB)

    Leila Moghaddam, B., E-mail: lmoghaddam@aut.ac.i [Faculty of Nuclear Engineering and Physics, Amirkabir Technical University (Tehran Polytechnic), Hafez Street, Tehran (Iran, Islamic Republic of); Setayeshi, Saeed; Maragheh, Mohammad G.; Gholipour, Reza [Faculty of Nuclear Engineering and Physics, Amirkabir Technical University (Tehran Polytechnic), Hafez Street, Tehran (Iran, Islamic Republic of)

    2009-11-15

    To optimize the cost effectiveness of {sup 186}Re and {sup 188}Re production, which have recently been used as radio pharmaceuticals for therapeutic purposes, we designed an artificial neural network (ANN) to evaluate the activity of combined {sup 186}Re + {sup 188}Re. One of the production ways is the (n,gamma) reaction of natural rhenium which leads to combined {sup 186}Re + {sup 188}Re. Using the counted activity of {sup 186}Re + {sup 188}Re mixtures by a well type isotope calibrator, the precise activity of {sup 186}Re and {sup 188}Re is obtained by the ANN. A back-propagation ANN was trained using 30 activities of mixed {sup 186}Re + {sup 188}Re. The performance of the ANN was tested by Early-Stopping validation method, and the ANN was optimized with respect to its architecture. The response of the ANN shows significant precision that may be used for medical application of {sup 186}Re + {sup 188}Re mixtures.

  5. Specific efficacy of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced neuroendocrine tumours of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Simon, Birgit [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2015-07-15

    Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with {sup 177}Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with {sup 177}Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25-41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were

  6. Bone marrow dosimetry in peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Forrer, Flavio; Krenning, Eric P.; Kooij, Peter P.; Bernard, Bert F.; Bakker, Willem H.; Teunissen, Jaap J.M.; Jong, Marion de; Kwekkeboom, Dik J. [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Konijnenberg, Mark [Mallinckrodt Medical BV, Research and Development, Petten (Netherlands); Lom, Kirsten van [Erasmus MC Rotterdam, Department of Haematology, Rotterdam (Netherlands); Herder, Wouter W. de [Erasmus MC Rotterdam, Department of Internal Medicine, Rotterdam (Netherlands)

    2009-07-15

    Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called ''remainder of the body'' to the bone marrow. Bone marrow aspirates were drawn in 15 patients after treatment with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment. A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (r=0.914, p<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose. (1) After PRRT with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone

  7. (44)Sc-PSMA-617 for radiotheragnostics in tandem with (177)Lu-PSMA-617-preclinical investigations in comparison with (68)Ga-PSMA-11 and (68)Ga-PSMA-617.

    Science.gov (United States)

    Umbricht, Christoph A; Benešová, Martina; Schmid, Raffaella M; Türler, Andreas; Schibli, Roger; van der Meulen, Nicholas P; Müller, Cristina

    2017-12-01

    The targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging ((68)Ga) and radionuclide therapy ((177)Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced (44)Sc (T 1/2 = 4.04 h) and investigated preclinically for its use as a diagnostic match to (177)Lu-PSMA-617. (44)Sc was produced at the research cyclotron at PSI by irradiation of enriched (44)Ca targets, followed by chromatographic separation. (44)Sc-PSMA-617 was prepared under standard labeling conditions at elevated temperature resulting in a radiochemical purity of >97% at a specific activity of up to 10 MBq/nmol. (44)Sc-PSMA-617 was evaluated in vitro and compared to the (177)Lu- and (68)Ga-labeled match, as well as (68)Ga-PSMA-11 using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu prostate cancer cells. In these experiments it revealed similar in vitro properties to that of (177)Lu- and (68)Ga-labeled PSMA-617. Moreover, (44)Sc-PSMA-617 bound specifically to PSMA-expressing PC-3 PIP tumor cells, while unspecific binding to PC-3 flu cells was not observed. The radioligands were investigated with regard to their in vivo properties in PC-3 PIP/flu tumor-bearing mice. (44)Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of (44)Sc-PSMA-617 resembled that of (177)Lu-PSMA-617 most closely, while the (68)Ga-labeled ligands, in particular (68)Ga-PSMA-11, showed different distribution kinetics. (44)Sc-PSMA-617 enabled distinct visualization of PC-3 PIP tumor xenografts shortly after injection, with increasing tumor-to-background contrast over time while unspecific uptake in the PC-3 flu tumors was not observed. The in vitro

  8. Occupational doses in neuroendocrine tumors by using {sup 177}Lu DOTATATE; Doses ocupacionais em tratamento de tumores neuroendocrinos utilizando {sup 17'}7Lu DOTATATE

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Gustavo Coelho Alves; Sa, Lidia Vasconcellos de, E-mail: gustavo@ird.gov.b, E-mail: lidia@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2011-10-26

    This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of {sup 177}Lu DOTATATE radiopharmaceutical which is a type of treatment presently used in the experimental form in Brazil and, therefore, not contemplated in norms or specific use. This research studied the occupational doses of this treatment and suggested guidelines or rules of procedures viewing the radiological protection of workers involved and the public. The treatment were followed up by using two types of radiation detection, one a scintillator and a Geiger-Muller, and the measurements were performed in a public hospital at Rio de Janeiro and the other in a private hospital at Sao Paulo. It was observed that the equivalent occupational doses can variate from 160 {mu}Sv to 450 {mu}Sv, in function of operator, of stage of manipulation, and of the administration method, which can be through the use of infusion pump or manual injection. The use of infusion pump is highly recommended and the hospitalization of the patient until the dose rate measured at 1 m does not surpass 20 {mu}Sv/h

  9. Comparison beta absorbed dose from 203Hg, 166Ho and 177LU isotopes in cortex and medulla in tree part kidney and integrated kidney using Monte Carlo method

    Directory of Open Access Journals (Sweden)

    Mohammad Mirzaei

    2015-04-01

    Full Text Available Background: Large quantities of radiopharmaceuticals prescribed for treatment and diagnosis are excreted through kidney. Therefore, radiation unwanted dose is created in kidney. As a result, exact calculation of prescribed medicine amount is important. In Mird pamphlet, 5 kidneys have considered in ellipsoidal shape that radiopharmaceutical is uniform distributed in them and gamma absorption fraction is calculated and recorded in the tables and the fraction of beta absorption is considered unit. While, kidney has internal organs and radioisotope is not uniform distributed in and beta absorbed fraction is not unit. Material and method: In this research, for the first time kidney is considered integrated shape and for the second time has been considered that it is consisted of three areas, pelvis, medulla and cortex. It is supposed that radiopharmaceutical is distributed in medulla. Then, beta absorbed dose is calculated in medulla and cortex using MCNPX code and is compared with integrated kidney results. Resuts: This research has been showed that beta absorbed dose from 203Hg, 166Ho and 177Lu isotopes in medulla is four times as much as dose in integrated kidney and beta dose in cortex is 0.004 to 0.012 times as much as beta dose in integrated kidney. Conclusion: Internal structure of kidney should be considered in simulation to achieve a more accurate prescribed dose. It is recommended that simulation results of three areas kidney are replaced with integrated kidney to prevent from renal toxicity.

  10. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

    Directory of Open Access Journals (Sweden)

    Huang FYJ

    2015-01-01

    Full Text Available Feng-Yun J Huang,1 Te-Wei Lee,2 Chih-Hsien Chang,2 Liang-Cheng Chen,2 Wei-Hsin Hsu,2 Chien-Wen Chang,1 Jem-Mau Lo1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; 2Institute of Nuclear Energy Research, Longtan, Taiwan Purpose: In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome was prepared and evaluated as a therapeutic agent for glioma.Materials and methods: The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats.Results: By using bioluminescent imaging, the well-established reporter cell line (F98luc showed a high relationship between cell number and its bioluminescent intensity (R2=0.99 in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05. As a result, the

  11. Development of a lyophilized formulation for preparing the radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20; Desarrollo de una formulacion liofilizada para la preparacion del radiofarmaco {sup 177}-DOTA-Anti-CD20

    Energy Technology Data Exchange (ETDEWEB)

    Serrano E, L. A.

    2015-07-01

    The radiolabeled proteins are molecules of interest in nuclear medicine for their diagnostic and therapeutic application in cancer. Antibodies, such as chimeric monoclonal antibody Anti-CD20 rituximab, have established themselves as suitable vectors of radionuclides (e.g. {sup 177}Lu) , introducing high affinity by the surface antigens over- expressed and widely distributed in cells involved in certain diseases. The aim of this work was to design, optimize and document the production process of radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20 for sanitary registration request to the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). First, a raw material analysis using the Ft-Mir technique and gamma spectrometry was performed. Then, was carried out the development of the lyophilized formulation for the preparation of {sup 177}Lu-DOTA-Anti-CD20, in which an ANOVA was performed where the dependent variable was the radiochemical purity. The optimal pharmaceutical formulation was: 5 mg DOTA-CD20 and 80 mg Mannitol to be reconstituted with 1 m L of acetate buffer 0.25 M, ph 7, with an incubation time of 15 min at 37 degrees Celsius in a dry bath. Once completed the development of the lyophilized formulation, we proceeded to the optimization of the production process, development and validation of the analytical method. Three batches were prepared under protocols of Good Manufacturing Practice, which met pre-established specifications as sterile and endotoxin-free of bacterial formulations, with greater that 95% of radiochemical purity. Currently, is conducting the study of shelf stability. Upon completion of the stability studies, the legal record of {sup 177}Lu-DOTA-Anti-CD20 will be integrated with documented evidence of the quality and stability of the formulation of this radiopharmaceutical. (Author)

  12. 肿瘤骨转移疼痛患者对188Re-HEDP的耐受性研究%The tolerance to 188Re-HEDP treatment in patients with bone pain from osseous metastases

    Institute of Scientific and Technical Information of China (English)

    程爱萍; 陈绍亮; 刘文官; 陈雪芬; 许长德

    2011-01-01

    Objective To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate(HEDP) in patients with bone pain caused by osseous metastases. Methods Thirty-one patients(10with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade Ⅲ- Ⅳ was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg.No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade Ⅰ leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade Ⅰ leucopenia including 1 alone with reversible grade Ⅲ thrombopenia. In the 40 MBq/kg group, reversible grade Ⅰ leucopenia and thrombopenia was observed in 1 patient and reversible grade Ⅱ leucopenia and thrombopenia in another patient. In the .50 MBq/kg group, 3 patients showed reversible grade Ⅱ leucopenia. The lowest level of thrombopenia was at week 4(143.5 × 109/L), leucopenia at week 6 (5.4 × 109/L) and anaemia at week 8(t = 3.1325, 3

  13. Formulation and evaluation of freeze-dried DOTMP kit for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP at the hospital radiopharmacy

    Energy Technology Data Exchange (ETDEWEB)

    Das, Tapas; Banerjee, Sharmila [Bhabha Atomic Research Centre, Radiopharmaceuticals Chemistry Section, Mumbai (India); Chakraborty, Sudipta [Bhabha Atomic Research Centre, Isotope Production and Applications Div., Mumbai (India); Sarma, Haladhar D. [Bhabha Atomic Research Centre, Radiation Biology and Health Sciences Div., Mumbai (India)

    2015-07-01

    The objective of the present work is to develop and evaluate freeze-dried DOTMP kit, which could be utilized for the convenient and single-step preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP, both of which have shown potential as alternative agents for metastatic bone pain palliation. Freeze-dried DOTMP kits, each comprising a lyophilized mixture of 20 mg DOTMP and 8.75 mg NaOH, were prepared. The kits were used for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP complexes. The agents were prepared by dissolving the lyophilized powder in 1 mL of normal saline and incubating with {sup 177}LuCl{sub 3} or {sup 153}SmCl{sub 3}, produced in-house, for 15 min at room temperature. Pharmacokinetic behavior and biological distribution of the agents were studied by carrying out biodistribution as well as scintigraphic studies in normal male Wistar rats. Shelf-life of the freeze-dried kits was also ascertained. Clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP complexes, comprising up to 3.7 GBq (100 mCi) of activity, were prepared with > 99% radiochemical purity using the freeze-dried kits. The complexes exhibited high in vitro stability when stored at room temperature. Biological studies showed selective skeletal accumulation and insignificant uptake of the radiotracers in any of the vital organs/tissue. The non-accumulated activity exhibited primary urinary clearance. The kits had a shelf-life of 2 years when stored at 4 C temperature. Freeze-dried DOTMP kits, suitable for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP, have been developed and the radiochemical and biological behaviors of the radiolabeled agents have been studied. The use of the kit at the hospital radiopharmacy is expected to make the preparations easy and convenient. This in turn will enable the widespread dissemination of these promising agents towards their application for regular use.

  14. The {sup 68}Ga/{sup 177}Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUV{sub max} values and absorbed dose estimates

    Energy Technology Data Exchange (ETDEWEB)

    Scarpa, Lorenza; Buxbaum, Sabine; Kendler, Dorota; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Fink, Katharina [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Medical University of Innsbruck, Department of Radiotherapy / Radiation Oncology, Innsbruck (Austria); Bektic, Jasmin; Horninger, Wolfgang [Medical University of Innsbruck, Department of Urology, Innsbruck (Austria); Gruber, Leonhard [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Lukas, Peter [Medical University of Innsbruck, Department of Radiotherapy / Radiation Oncology, Innsbruck (Austria)

    2017-05-15

    A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Ten consecutive mCRPC patients were selected for {sup 177}Lu-PSMA617 therapy on the basis of PSMA-targeted {sup 68}Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging ({sup 68}Ga-PSMA-HBED-CC and {sup 18}F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to {sup 177}Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed. {sup 177}Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased {sup 177}Lu-PSMA617 and {sup 68}Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions. Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following {sup 177}Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study. (orig.)

  15. Outcome of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

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    Ezziddin, Samer; Khalaf, Feras; Vanezi, Maria; Haslerud, Torjan; Zreiqat, Abdullah Al; Biersack, Hans-Juergen; Sabet, Amir [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Willinek, Winfried [University Hospital, Department of Radiology, Bonn (Germany)

    2014-05-15

    The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with {sup 177}Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with {sup 177}Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial {sup 99m}Tc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis

  16. Synthesis and stability test of radioimmunoconjugate 177Lu-DOTA-F(ab′2-trastuzumab for theranostic agent of HER2 positive breast cancer

    Directory of Open Access Journals (Sweden)

    Sandra Hermanto

    2016-10-01

    Full Text Available The use of trastuzumab as intact IgG labeling radionuclide for HER2 positive breast cancer theranostic agent is not ideal because it is slowly eliminated from the blood and normal tissues resulting in low tumor/blood (T/B and tumor/normal tissue (T/NT ratios. To overcome this limitation, we developed the trastuzumab F(ab′2 fragments and radiolabeling of the fragments by β and γ-particle of Lutetium-177. F(ab2 fragments were produced by digestion of trastuzumab IgG (Herceptin with pepsin for 18 h at 37 °C. The F(ab′2 fragment fractionated in PD-10 column, followed by the conjugation with 2-(4-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA as a metal chelator and radiolabeling with 177LuCl3. Molecular weight of fragments was calculated by LCMS (Liquid Chromatography Mass Spectroscopy and the radiochemical purity was evaluated by ITLC-SG (Instan Thin Layer Chromatography. Our study showed that the purity of F(ab′2 fragment generated by PD-10 fractions was >98% and the molecular weight of F(ab′2 was 98.35 kDa. The average numbers of pSCN-Bn-DOTA chelates per antibody fragment were 5.03 ± 1.5 and the optimum conjugation reactions was performed at molar ratio 20:1 (chelator to antibody. The stability test of the radioimmunoconjugate in the human serum albumin (HSA at 37 °C showed the radiochemical purity was 91.96 ± 0.26% after 96 h storage. This indicated that the radioimmunoconjugate is relatively stable when applied to the human body's physiological condition.

  17. Influence of biological assay conditions on stability assessment of radiometal-labelled peptides exemplified using a {sup 177}Lu-DOTA-minigastrin derivative

    Energy Technology Data Exchange (ETDEWEB)

    Ocak, Meltem [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria); Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, 34116, Istanbul (Turkey); Helbok, Anna; Guggenberg, Elisabeth von [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria); Ozsoy, Y. [Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, 34116, Istanbul (Turkey); Kabasakal, Levent [Department of Nuclear Medicine, Cerrahpasa Medical Faculty, 34098, Istanbul (Turkey); Kremser, Leopold [Division of Clinical Biochemistry, Protein Micro-Analysis Facility, Biocenter, Medical University Innsbruck, A-6020, Innsbruck (Austria); Decristoforo, Clemens, E-mail: clemens.decristoforo@uki.a [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria)

    2011-02-15

    Introduction: Lack of correlation between in vitro and in vivo stability is a general problem for the development of radiopeptides especially in the case of minigastrin derivatives for therapeutic applications. In this study, we compared the influence of experimental conditions on radiopeptide stability results in vitro using a model Minigastrin (MG) analogue labelled with Lu-177. Additionally, we attempted to characterize the main serum enzymatic cleavage sites by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) analysis. Methods: In vitro stability of a DOTA-minigastrin derivative ({sup 177}Lu-DOTA-His-His-Glu-Ala-Tyr-Gly-Trp-NIe-Asp-Phe-NH{sub 2}) was tested in serum, rat tissue homogenates and two different standardised enzymatic mixtures. Quantification of the metabolised radiopeptides at different time intervals was performed using reversed-phase high-performance liquid chromatography (RP-HPLC). Metabolites were characterised by MALDI-TOF-MS. Urine was collected after 15 min p.i. into the mice and compared with in vitro metabolites by RP-HPLC. Results: Faster degradation of the radiopeptide was found in blood in comparison with plasma and serum incubation and in components from rats faster than from human origin. Fast degradation was observed in kidney and liver homogenates as well as in standardised enzymatic mixtures, also revealing variations in the metabolic profile. In urine, no intact peptide was detected already 5 min post injection. MALDI-TOF-MS revealed major cleavage sites at the carboxy terminus of the peptide. Conclusion: Very variable results may be found when different kind of incubation media for testing radiopeptide stabilities is used. Serum incubation studies may overestimate stability; therefore, results should be interpreted with care and combined with alternative in vitro and in vivo investigations.

  18. Rapid blood clearance and lack of long-term renal toxicity of {sup 177}Lu-DOTATATE enables shortening of renoprotective amino acid infusion

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava; Eu, Peter [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Jackson, Price [Peter MacCallum Cancer Centre, Department of Physical Sciences, Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); The University of Melbourne, Departments of Medicine and Radiology, Melbourne (Australia); Beauregard, Jean-Mathieu [Universite Laval, Department of Radiology, Quebec City (Canada); Zannino, Diana [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne (Australia)

    2013-12-15

    The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of {sup 177}Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation. (orig.)

  19. {sup 99m}Tc(V)DMSA quantitatively predicts {sup 188}Re(V)DMSA distribution in patients with prostate cancer metastatic to bone

    Energy Technology Data Exchange (ETDEWEB)

    Blower, P.J.; Kettle, A.G.; O' Doherty, M.J.; Coakley, A.J. [Kent and Canterbury Hospital, Canterbury (United Kingdom). Nuclear Medicine Dept.; Knapp, F.F. Jr. [Nuclear Medicine Group, Oak Ridge National Lab., Oak Ridge, TN (United States)

    2000-09-01

    Rhenium-188 dimercaptosuccinic acid complex [{sup 188}Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent {sup 99m}Tc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if {sup 99m}Tc(V)DMSA could be used to predict tumour and kidney retention of {sup 188}Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of {sup 99m}Tc(V)DMSA and {sup 188}Re(V)DMSA. This would determine whether a scan with {sup 99m}Tc(V)DMSA, could be used to identify patients for whom {sup 188}Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in {sup 188}Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent {sup 99m}Tc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq {sup 99m}Tc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq {sup 188}Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the {sup 188}Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on {sup 188}Re scans than on {sup 99m}Tc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for {sup 188}Re than for {sup 99m}Tc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were

  20. The experimental study on the radioimmunotherapy of the nasopharyngeal carcinoma overexpressing HER2/neu in nude mice model with intratumoral injection of {sup 188}Re-herceptin

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    Li Guiping [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China) and Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China)]. E-mail: ligp@fimmu.com; Wang Yongxian [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, the Chinese Academy of Sciences, Shanghai, 201800 (China)]. E-mail: yongxianw@163.com; Huang Kai [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Hui [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Peng Wuhe [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Chunfu [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China)

    2005-01-01

    The therapeutic efficacy of radioimmunotherapy (RIT) of {sup 188}Re-labeled herceptin, which is a humanized anti-p185-HER2/neu monoclonal antibody (mAb), was studied. The nude mice bearing nasopharyngeal carcinoma (NPC) expressing HER2/neu protooncogene were injected with {sup 188}Re-herceptin intratumorally and intravenously. The biodistribution was observed on day 2 (n=3). The tumor growth inhibition rate (IR) was determined by measurement of tumor volume. In the intratumorally treated mice, tumor uptake of {sup 188}Re-herceptin was significantly greater than in the intravenously treated mice [11.53% injected dose (ID)/g vs. 2.79% ID/g at 48 h], and lower normal organ uptake was also seen. The intratumoral administration of {sup 188}Re-herceptin caused greater inhibition of tumor growth at the fourth week as compared to the intravenous administration. It is concluded that intratumoral administration of {sup 188}Re-herceptin makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy for NPC overexpressing HER2/neu.

  1. A YAP camera for the biodistribution of {sup 188}Re conjugated with Hyaluronic-Acid in 'in vivo' systems

    Energy Technology Data Exchange (ETDEWEB)

    Antoccia, A. [Department of Biology, Roma3 University (Italy); INFN, Roma3 (Italy); Baldazzi, G. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); Banzato, A. [Department of Oncology and Surgical Sciences, Padova University (Italy); Bello, M. [INFN, National Laboratories, Legnaro (Italy); Department of Physics, Padova University (Italy); Boccaccio, P. [INFN, National Laboratories, Legnaro (Italy); Bollini, D. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); De Notaristefani, F. [INFN, Roma3 (Italy); Department of Electronic Engineering, Roma3 University and INFN (Italy); Mazzi, U. [Department of Pharmaceutical Sciences, Padova University (Italy); Alafort, L.M. [Department of Pharmaceutical Sciences, Padova University (Italy); Moschini, G. [INFN, National Laboratories, Legnaro (Italy); Department of Physics, Padova University (Italy); Navarria, F.L. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); Pani, R. [Department of Experimental Medecine and Pathology, Roma1 University (Italy); INFN, Roma1 (Italy); Perrotta, A. [INFN, Bologna (Italy)]. E-mail: perrotta@bo.infn.it; Rosato, A. [Department of Oncology and Surgical Sciences, Padova University (Italy); Istituto Oncologico Veneto, Padova (Italy); Tanzarella, C. [Department of Biology, Roma3 University (Italy); Uzunov, N.M. [INFN, National Laboratories, Legnaro (Italy); Dept. Natural Sciences, Shumen Univ. (Bulgaria)

    2007-02-01

    The aim of the SCINTIRAD experiment is to determine the radio-response of {sup 188}Rhenium (Re) in in vitro cells and the biodistribution in different organs of in vivo mice, and subsequently to assess the therapeutic effect on liver tumours induced in mice. Both the {gamma}- and {beta}- emissions of {sup 188}Re have been exploited in the experiment. The in vivo biodistribution in mice was studied also with a {gamma}-camera using different parallel hole collimators. In the {sup 188}Re spectrum, while the 155 keV {gamma}-peak is useful for imaging, the photons emitted at larger energies and the {beta}-particles act as noise in the image reconstruction. The {gamma}-cameras previously used to image biodistributions obtained with {sup 99}Tc are, therefore, not optimized for use with {sup 188}Re. A new setup of the {gamma}-camera has been studied for {sup 188}Re: 66x66 YAP:Ce crystals (0.6x0.6x10 mm{sup 3}, 5 {mu}m optical insulation) guarantee a FOV of 40x40 mm{sup 2}, a Hamamatsu R2486 PSPMT, 3 in. diameter, converts their light into an electrical signal and allows reconstructing the spatial coordinates of the light spot; incoming photon directions are selected through a lead collimator with 1.5 mm diameter hexagonal holes, 0.18 mm septa, 40 mm thickness. Using this setup, results have been obtained both with {sup 99}Tc filled and {sup 188}Re filled capillaries and wells. The energy spectrum of the collected photons and the spatial resolutions obtainable with the {sup 188}Re source will be presented.

  2. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and {sup 18}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Ianniello, Annarita; Sansovini, Maddalena; Severi, Stefano; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Unit, Meldola (Italy); Grana, Chiara Maria [European Institute of Oncology Milan (IEO), Division of Nuclear Medicine, Milan (Italy); Massri, Katrin [Ospedale San Luca, Nuclear Medicine, Department of Radiology, Lucca (Italy); Bongiovanni, Alberto [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Antonuzzo, Lorenzo [AOU Careggi, SC Oncologia Medica 1, Firenze (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Sarnelli, Anna [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela; Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2016-06-15

    Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and {sup 18}F-FDG PET as prognostic factors in patients with advanced TC or AC. A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients. The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group. Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of

  3. Role of {sup 18}FDG PET/CT in patients treated with {sup 177}Lu-DOTATATE for advanced differentiated neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Matteucci, Federica [Cancer Institute of Romagna (IRST), Unit of Radiometabolic Medicine, Meldola, FC (Italy); Nanni, Oriana; Scarpi, Emanuela [Cancer Institute of Romagna (IRST), Unit of Biostatistics and Clinical Trials, Meldola, FC (Italy); Bodei, Lisa; Gilardi, Laura; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Nicoletti, Stefania [Cancer Institute of Romagna (IRST), Unit of Medical Oncology, Meldola, FC (Italy)

    2013-06-15

    The prognostic value of FDG PET for neuroendocrine tumours (NETs) has been reported. In this study we evaluated the role of FDG PET in predicting response and progression-free survival (PFS) after {sup 177}Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced well-differentiated grade 1/2 NETs. We retrospectively evaluated 52 patients with progressive advanced NETs overexpressing somatostatin receptors and treated with Lu-PRRT with a cumulative activity up to 27.7 GBq divided into five courses. According to WHO 2010/ENETS classification, patients were stratified into two groups: those with grade 1 tumour (Ki-67 index {<=}2 %, 19 patients), and those with grade 2 tumour (Ki-67 index >3 % to <20 %, 33 patients). On the basis of the FDG PET scan, 33 patients were classified as PET-positive (PET+) and 19 as PET-negative (PET-). FDG PET was positive in 57 % of patients with grade 1 NET and in 66 % of patients with grade 2 NET, and the rates of disease control (DC, i.e. complete response + partial response + stable disease) in grade 1 and grade 2 patients were 95 % and 79 %, respectively (P = 0.232). In PET- and PET+ patients, the DC rates were 100 % and 76 % (P = 0.020) with a PFS of 32 and 20 months, respectively (P = 0.033). Of the PET+ patients with grade 1 NET, 91 % showed disease control, whereas about one in three PET+ patients with grade 2 NET (32 %) progressed after Lu-PRRT (DC rate 68 %). These results suggest that FDG PET evaluation is useful for predicting response to Lu-PRRT in patients with grade 1/2 advanced NETs. Notably, none of PET- patients had progressed at the first follow-up examination after Lu-PRRT. Grade 2 NET and PET+ (arbitrary SUV cutoff >2.5) were frequently associated with more aggressive disease. PET+ patients with grade 2 NET, 32 % of whom did not respond to Lu-PRRT monotherapy, might benefit from more intensive therapy protocols, such as the combination of chemotherapy and PRRT. (orig.)

  4. Radiosynovectomy of Painful Synovitis of Knee Joints Due to Rheumatoid Arthritis by Intra-Articular Administration of (177)Lu-Labeled Hydroxyapatite Particulates: First Human Study and Initial Indian Experience.

    Science.gov (United States)

    Shinto, Ajit S; Kamaleshwaran, K K; Chakraborty, Sudipta; Vyshakh, K; Thirumalaisamy, S G; Karthik, S; Nagaprabhu, V N; Vimalnath, K V; Das, Tapas; Banerjee, Sharmila

    2015-01-01

    The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using (177)Lu-labeled hydroxyapatite ((177)Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of (177)Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of (177)Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those with more advanced changes

  5. Pre-therapeutic dosimetry of normal organs and tissues of {sup 177}Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, Levent; AbuQbeitah, Mohammad; Ayguen, Aslan; Yeyin, Nami [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Ocak, Meltem [Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Demirci, Emre [Sisli Etfal Training and Research Hospital, Department of Nuclear Medicine, Istanbul (Turkey); Toklu, Turkay [Yeditepe University Medical Faculty, Department of Nuclear Medicine, Istanbul (Turkey)

    2015-12-15

    {sup 177}Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of {sup 177}Lu-labeled PSMA ligand. The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected {sup 177}Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. Our first results suggested that {sup 177}Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are

  6. Studies on biodistribution and imaging of 188Re labeled insulin-like growth factor-1 analogue in nude mice bearing human pancreatic carcinoma%188Re-胰岛素样生长因子1类似物在荷人胰腺癌裸鼠体内分布及其显像研究

    Institute of Scientific and Technical Information of China (English)

    邓胜明; 张玮; 章斌; 罗贤文; 吴翼伟

    2008-01-01

    目的 研究188Re标记胰岛素样生长因子l类似物(IGF-1A)在荷人胰腺癌裸鼠体内的分布及其显像.方法 ①直接法标记188Re-IGF-1A并测定标记率.②建立荷人胰腺癌Patu8988裸鼠模型.③188Re-IGF-1A经瘤内注射荷人胰腺癌裸鼠瘤内,分别于注射后15 min、1 h、4 h、24 h、3 d、5 d进行SPECT平面显像.④188ReO4-经瘤内注射后15 min、1 h、2 h、4 h、24 h进行显像,取各时间组裸鼠(n=4)脏器和肿瘤组织,计算每克组织百分注入剂量(%ID/g)及肿瘤/非肿瘤组织放射性摄取比值(T/NT).结果 ①188Re-IGF-1A标记率为(94.07±0.32)%.②瘤内注射188Re-IGF-1A后,肿瘤部位放射性积聚量4 h内差异无统计学意义(F=1.622,P>0.05),且随时间延长,肿瘤与其他脏器的T/NT呈上升趋势,其中肿瘤/肌肉在5 d时最高,达到6531.79±4930.26.③瘤内注射188ReO4-后,在体内初始主要分布于甲状腺、胃、肿瘤、血液,随时间延长,肿瘤部位放射性计数迅速下降.④在24 h,瘤内注射188Re-IGF-1A组肿瘤及肾脏内%ID/g较188ReO4-组高,两者有统计学差异(t=5.877,t=13.287,P<0.01);两组肿瘤内%ID/g比值在24 h达到最高,为74.10倍.⑤瘤内注射188Re-IGF-1A后,SPECT平面显像见瘤内浓聚,5 d时仅见肿瘤部位显影.结论 188Re-IGF-1A对胰腺癌具有良好的亲和力,在肿瘤部位有较高的T/NT,可望作为胰腺癌治疗的药物.%Objective To evaluate the biodistribution and planar gamma carnera jmaging characteristics of 188Re labeled insulin-like growth factor 1 analogue(188Re-IGF-1A)in tumor-bearing mice.Methods ①To label IGF-1A with 188Re directly and to determine the labeling efficiency.②To establish nude mice model which beating human pancreatic carcinoma cell Patu8988.③To scan those nude mice at 15 min,1 h,4 h,24 h,3 d and 5 d after intratumor injection with 188Re-IGF-1A into their tumors.④To scan those nude mice at 15min,1 h,2h,4 h and24 h after intratumor injection with 188ReO4-into their

  7. In vitro and in vivo evaluation of {sup 177}Lu- and {sup 9}Y-labeled E. coli heat-stable enterotoxin for specific targeting of uroguanylin receptors on human colon cancers

    Energy Technology Data Exchange (ETDEWEB)

    Giblin, Michael F. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States) and Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)]. E-mail: giblinm@health.missouri.edu; Sieckman, Gary L. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Shelton, Tiffani D. [Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Hoffman, Timothy J. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Forte, Leonard R. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Medical Pharmacology and Physiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Volkert, Wynn A. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)

    2006-05-15

    The human E. coli heat-stable enterotoxin (ST{sub h}, amino acid sequence N{sup 1}SSNYCCELCCNPACTGCY{sup 19}) binds specifically to the guanylate cyclase C (GC-C) receptor, which is present in high density on the apical surface of normal intestinal epithelial cells as well as on the surface of human colon cancer cells. Analogs of ST{sub h} are currently being used as vectors targeting human colon cancers. Previous studies in our laboratory have focused on development of {sup 111}Indium-labeled ST{sub h} analogs for in vivo imaging applications. Here, we extend the scope of this work to include targeting of the therapeutic radionuclides {sup 9}Y and {sup 177}Lu. The peptide DOTA-F{sup 19}-ST{sub h}(1-19) was synthesized using conventional Fmoc-based solid-phase techniques and refolded in dilute aqueous solution. The peptide was purified by RP-HPLC and characterized by MALDI-TOF MS and in vitro receptor binding assay. The DOTA-conjugate was metallated with nonradioactive Lu(III)Cl{sub 3} and Y(III)Cl{sub 3}, and IC{sub 5} values of 2.6{+-}0.1 and 4.2{+-}0.9 nM were determined for the Lu- and Y-labeled peptides, respectively. {sup 177}Lu(III)Cl{sub 3} and {sup 9}Y(III)Cl{sub 3} labeling yielded tracer preparations that were inseparable by C18 RP-HPLC, indicating that putative differences between Lu-, Y- and In coordination spheres are not observed in the context of labeled ST{sub h} peptides. In vivo biodistribution studies of the {sup 177}Lu-labeled peptide in severe combined immunodeficient (SCID) mice bearing T-84 human cancer tumor xenografts showed rapid clearance from the bloodstream, with >90 %ID in the urine at 1 h pi. Localization of the tracer within tumor xenografts was 1.86{+-}0.91 %ID/g at 1 h pi, a value higher than for all other tissues with the exception of kidney (2.74{+-}0.24 %ID/g). At 24 h pi, >98 %ID was excreted into the urine, and 0.35{+-}0.23 %ID/g remained in tumor, again higher than in all other tissues except kidney (0.91{+-}0.46 %ID

  8. Preparation of {sup 188}W/{sup 188}Re generators at base of {sup 188}W-titanium and zirconium tungstates by means of the sol-gel method; Preparacion de generadores {sup 188}W/{sup 188}Re a base de {sup 188}W-tungstenatos de titanio y zirconio mediante el metodo sol-gel

    Energy Technology Data Exchange (ETDEWEB)

    Rosales T, C.J. [Universidad Autonoma del Estado de Mexico, Paseo Colon esq. Paseo Tollocan, 50120 Toluca, Estado de Mexico (Mexico); Monroy G, F.; Rivero G, T.; Rojas N, P. [ININ, Carretera Mexico-Toluca S/N, 52750 Estado de Mexico (Mexico)]. e-mail: c.j.rt@hotmail.com

    2007-07-01

    The {sup 188}Re possess nuclear characteristics that make it attractive for therapeutic application, given their {beta}{sup -} particle emission of high energy 0.764 keV besides the possibility of being able to unite to different ligands. The {sup 188}Re commercial generators use a chromatographic column loaded with alumina where the {sup 188}W is adsorbed and the {sup 188}ReO{sub 4}{sup -} eluted by means of a saline solution. The low capacity of the alumina that only it allows adsorber 0.2% in weight of {sup 188}W demand to use {sup 188}W of a high specific activity. An alternative of production of {sup 188}W / {sup 188}Re generators consists on substituting the high specific activity, for the use of a bigger quantity of {sup 188}W by means of the use of gels with the aid of tungstates. For that, in this work it intends the study of the gel synthesis conditions of {sup 188}W titanium and zirconium tungstates and their effect in the acting of the {sup 188}W / {sup 188}Re generators. The gels were synthesized by means of the sol-gel method starting from titanium and zirconium alcoxis, and solutions of {sup 188}W-sodium tungstates to different pH's. The use of the sol-gel methodology diminishes the time of synthesis of these gels almost in 60% in relation to the precipitation method commonly used. (Author)

  9. Preparation, biodistribution, and dosimetry of {sup 188}Re-Labeled MoAb ior cea1 and its f(ab'){sub 2} fragments by avidin-biotin strategy

    Energy Technology Data Exchange (ETDEWEB)

    Ferro-Flores, Guillermina E-mail: gff@nuclear.inin.mx; Pimentel-Gonzalez, Gilmara; Gonzalez-Zavala, Maria Antonia; Murphy, Consuelo Arteaga de; Melendez-Alafort, Laura; Tendilla, Jose I.; Croft, Barbara Y

    1999-01-01

    The biotinylated monoclonal antibody (MoAb) ior cea1 and its F(ab'){sub 2} fragments were labeled with Re-188 by combination of avidin-biotin strategy. {sup 188}Re-MoAb, {sup 188}Re-MoAb-biotin, {sup 188}Re-F(ab'){sub 2}, and {sup 188}Re-F(ab'){sub 2}-biotin preparations were produced for these studies with specific activities of 1.30{+-}0.18 GBq/mg and from instant freeze-dried kit formulations using ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) as a weak competing ligand. There were no significant differences (p>0.05) between the biodistribution in mice of biotinylated and unbiotinylated {sup 188}Re-labeled immunoconjugates. When avidin was injected as a chase after injection of {sup 188}Re-MoAb-biotin or {sup 188}Re-F(ab'){sub 2}-biotin, the blood radioactivity level decreased approximately 75% (cumulated activity) and the effective dose decreased almost 25% with respect to that of the radioimmunoconjugates in which the chase effect was not used. Our results suggest that {sup 188}Re-labeled biotinylated MoAb ior cea1 and its F(ab'){sub 2} fragments prepared by this method are stable complexes in vivo.

  10. Development of pharmaceuticals with radioactive rhenium for cancer therapy. Production of {sup 186}Re and {sup 188}Re, synthesis of labeled compounds and their biodistributions

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    Production of the radioactive rhenium isotopes {sup 186}Re and {sup 188}Re, and synthesis of their labeled compounds have been studied together with the biodistributions of the compounds. This work was carried out by the Working Group on Radioactive Rhenium, consisting of researchers of JAERI and some universities, in the Subcommittee for Production and Radiolabeling under the Consultative Committee of Research on Radioisotopes. For {sup 186}Re, production methods by the {sup 185}Re(n,{gamma}){sup 186}Re reaction in a reactor and by the {sup 186}W(p,n){sup 186}Re reaction with an accelerator, which can produce nocarrier-added {sup 186}Re, have been established. For {sup 188}Re, a production method by the double neutron capture reaction of {sup 186}W, which produces a {sup 188}W/{sup 188}Re generator, has been established. For labeling of bisphosphonate, DMSA, DTPA, DADS, aminomethylenephosphonate and some monoclonal antibodies with the radioactive rhenium isotopes, the optimum conditions, including pH, the amounts of reagents and so on, have been determined for each compound. The biodistributions of each of the labeled compounds in mice have been also obtained. (author)

  11. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity {sup 86}Y- or {sup 177}Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Lee, Sang-gyu; Punzalan, Blesida; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Xu, Hong; Guo, Hong-fen [Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Chalasani, Sandhya; Carrasquillo, Jorge A. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Fung, Edward K. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Jungbluth, Achim [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Zanzonico, Pat B.; O' Donoghue, Joseph [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Smith-Jones, Peter M. [Stony Brook University, Department of Psychiatry and Behavioral Science, Stony Brook, NY (United States); Stony Brook University, Department of Radiology, Stony Brook, NY (United States); Wittrup, K.D. [Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Cambridge, MA (United States); Cheung, Nai-Kong V. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States)

    2016-05-15

    GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens {sup 177}Lu-or {sup 86}Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq {sup 177}Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm{sup 3}) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm{sup 3} tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten {sup 86}Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. (orig.)

  12. In vivo distribution and metabolism of 188Re-iodized oil-carboxymethyl chitosan-nanoparticles in the S180 tumor-bearing mice%188Re-碘化油-羧甲基壳聚糖-纳米微粒在荷S180肉瘤小鼠体内分布与代谢

    Institute of Scientific and Technical Information of China (English)

    王洪震; 贾正平; 郝彦明; 钱荣勋; 董启榕; 徐又佳

    2011-01-01

    背景:188Re标记的放射性药物在体内发生 Re核索脱落也不会对人体造成严重的辐射损伤.188Re-碘化油有可能成为一种具有临床应用价值的内照射治疗肿瘤的药物.目的:研究羧甲基壳聚糖载药纳米微球的制备及在荷S180肉瘤小鼠体内分布及代谢.方法:将188Re-碘化油通过羧甲基壳聚糖纳米微球包裹,将其注射于荷S180肉瘤小鼠体内,通过 SPECT法观察188Re-碘化油-羧甲基壳聚糖-纳米微粒在荷瘤鼠中的显像.结果与结论:采用羧甲基壳聚糖-纳米微粒对188Re-碘化油标记率达(94.9±0.2)%;肝、肾是188Re-碘化油-羧甲基壳聚糖-纳米微粒的主要分布器官;骨、肌肉、小肠等脏器摄取较少,且随着时间的延长而下降;脑内未测得放射性,各比值随着时间的延长而有增加的趋势,分别在注射显像剂后6~10 h达到峰值.说明羧甲基壳聚糖-纳米微粒对188Re的包裹效果良好;188Re-碘化油-羧甲基壳聚糖-纳米微粒在正常骨、肌肉、小肠基本无摄取,但48 h浓聚于肉瘤组织内,肿瘤与脾、胃、肠、股骨、肌肉、脂肪组织放射性比值高.%BACKGROUND: 188Re labeled radiopharmaceuticals in body occur Re nuclear cable off which will not cause serious radiation damage of the body. 188Re-iodized oil may become a kind of clinical application of drugs within the radiation treatment of cancer.OBJECTIVE: To study preparation of drug-loaded nano-carboxymethyl chitosan microspheres and in vivo distribution and metabolism in the S180 tumor-bearing mice.METHODS: 188Re-lipiodol was wrapped by carboxymethyl chitosan nanoparticles, the wrapped 188Re-lipiodol was injected into the mice bearing S180 sarcoma. Imaging of 188Re-iodized oil-carboxymethyl chitosan-nanoparticles in the tumor-bearing mice was observed by single photon emission computed tomography.RESULTS AND CONCLUSION: Labeling rate of 188Re-lipiodol which labeled by carboxymethyl chitosan-nanoparticles was (94.9±0

  13. {sup 188}Re-HTDD-lipiodol solution as a new therapeutic agent for transhepatic arterial administration in liver cancer: a preclinical study using liver-cancer model in rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Paeng, J. C.; Jeong, J. M.; Lee, Y. S. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)] [and others

    2001-07-01

    {sup 188}Re-HTDD-lipiodol solution was developed and reported to be a new therapeutic material for transhepatic arterial embolization (TAE) of liver cancer. In this study we compared the tissue retention of {sup 188}Re-HTDD-lipiodol with that of {sup 188}Re-TDD-lipiodol using liver-cancer model in rabbit. Cancer cell line VX2 was inoculated into 7 rabbits and grown up to larger than 3 cm. TAE was performed with {sup 188}Re-TDD-lipiodol in 3 rabbits and with {sup 188}Re-HTDD-lipiodol in 4 rabbits. Conjugated planar scans were performed at 1, 2, 6, 24, 48 hours after TAE. From these images, the mean life of radioactivity retention in tumor was calculated, and the required dose for human application as also calculated from the mean life and MIRDOSE3 software. The mean lifes of radioactivity in liver were 10.2{+-}1.0 hr in TDD group and 17.6{+-}0.8 hr in HTDD group (p<0.001). The required dose for the tumor to be irradiated 50 Gy of radiation was calculated to be 18 mCi of {sup 188}Re-HTDD-lipiodol for 5.7 cm-sized tumor and 88 mCi for 9,7 cm-sized tumor. By the introduction of long chain alkyl group, {sup 188}Re-HTDD-lipiodol showed significantly better tumor retention than that of {sup 188}Re-TDD-lipiodol. And the required dose of radiation for human application was calculated to be 18 {approx} 88 mCi when using {sup 188}Re-HTDD-lipiodol.

  14. Dosimetry and microdosimetry of {sup 188} Re-anti-CD20 and {sup 131} I-anti-CD20 for the treatment of No Hodgkin lymphomas; Dosimetria y microdosimetria del {sup 188} Re-anti-CD20 y {sup 131} I-anti-CD20 para el tratamiento de linfomas No Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Torres G, E

    2007-07-01

    The purpose of this investigation was to prepare {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20 and to estimate the radiation absorbed dose at macro- and micro- level during a NHL treatment. The work was divided in 4 general objectives: 1) preparation of {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20, 2) application in patients to obtain biokinetic parameters and estimate the organ absorbed doses 3) estimation of the cellular dosimetry using the MIRD methodology and the MCNP4C2 code and 4) estimation of the cellular microdosimetry using the NOREC code. {sup 188}Re-anti-CD20 was prepared by a direct labelling method using sodium tartrate as a weak ligand. To evaluate the biological recognition a comparative study of the in vitro binding of {sup 188}Re-anti-CD20, {sup 125}I-anti-CD20 (positive control) and {sup 188}Re-anti-CEA (negative control) to normal B Iymphocytes was performed. Biodistribution studies in normal mice were accomplished to assess the in vivo Re-anti-CD20 complex stability. The binding of ' Re-anti-CD20 to cells was in the same range as '251-anti-CD20 (>80%) considered as the positive control. {sup 188}Re-anti-CD20 and '3'1-anti-CD20 prepared were administered in patients diagnosed with B cell NHL at the Centro Medico Siglo XXI (IMSS). The protocol was approved by the hospital's Medical Ethics Committee. AJI patients signed a consent form after receiving detailed information on the aims of the study. N data were the input for the OLINDA/EXM software to calculate the radiation absorbed dose to organs and whole body. Dosimetric studies indicate that after administration of 6.4 GBq and 4.87 to 8.75 GBq of '3'1-anti-CD20 and {sup 188}Re-anti-CD20 respectively, the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies. The calculated organ absorbed doses indicate that {sup 188}Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or

  15. Development of activity standard for 90Y microspheres

    CSIR Research Space (South Africa)

    Mo, L

    2005-08-01

    Full Text Available 90Y is a therapeutic radiopharmaceuticals used in the treatment of liver cancer following implantation via a catheter in the hepatic artery, 90Y microspheres are embolised in the microvasculature of liver cancer where they irradiate the tumour by a...

  16. 温敏型壳聚糖介入核素188Re内照射抗小鼠移植性肝癌(H22)%Invistagation of antitumor efffect of internal Irradiation of Interventional Radionuclide 188 Re in Thermosensitive Chitosan on Mouse Transplanted Tumor H22

    Institute of Scientific and Technical Information of China (English)

    董峰; 郭红云; 张永东; 梅澍

    2011-01-01

    Objectives To study the inhibitory activity of internal irradiation of interventional radionuclide 188 Re in thermosensitive chitosan on mouse transplanted tumor H22 (liver cancer).Method The tumor-bearing mice were divided into 7 groups randomly, including model control, 188Re(0.1mCi) group, 188Re-S(0.1mCi) group, 188Re + CS(0.1mCi)group, 188Re + CS (0.2mCi)group, 188Re-S + CS 0.1mCi)and188Re-S + CS(0.2mCi)group.The mice tumor was injected with corresponding reagent respectively, and the inhibitoy rate of tumor was observed after administrated.Results The growth of tumors in 188Re + CS group and 188Re-S + CS group was slowed.the tumor inhibitory rate reached the highest level after 6 days therapy, which respectively was 67.35% and 67.81%.Conclusions Internal irradiation of interventional radionuclide 188 Re in thermosensitive ehitosan had the effect of inhibitory mice liver cancer.%目的 研究温敏型壳聚糖(chitonsan CS)介入核素188Re内照射对小鼠移植性肝RW(H22)的抑制作用.方法 建立小鼠肝癌(H22)模型后随机分成7组,即模型对照组、.88Re(0.1mCi)组、188Re-S (0.1mCi)组、188Re +CS (0.1 mci)组、188Re + CS (0.2mCi)组、188Re+硫胶体+壳聚糖(188Re-S + CS 0.1 mCi)组和188Re-S + CS (0.2mCi )组.各组动物瘤内分别注射相应试药,测定肿瘤抑制率.结果 188Re + CS组和188Re-S + CS组肿瘤生长速度减慢,肿瘤生长延迟,肿瘤抑制率在治疗后6d最高,抑制率分别为67.35%和67.81%.结论 温敏型壳聚糖介入核素188Re内照射对小鼠肝癌(H22)具有一定的抑制作用.

  17. Myeloablative radioimmunotherapy with {sup 188}Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-{alpha}; Myeloablative Radioimmuntherapie mit {sup 188}Re-CD66mAb vor Stammzelltransplantation. Kein Anstieg proinflammatorischer Zytokinspiegel von TNF-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Mutschler, J.; Reske, S.N. [Universitaetsklinik Ulm (Germany). Klinik fuer Nuklearmedizin; Steinbach, G. [Universitaetsklinik Ulm (Germany). Abt. Klinische Chemie; Bunjes, D. [Universitaetsklinik Ulm (Germany). Medizinische Klinik III; Buchmann, I. [Universitaetsklinik Heidelberg (Germany). Abt. fuer Nuklearmedizin

    2009-07-01

    Tumour necrosis factor-{alpha} (TNF-{alpha}) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with {sup 188}Re-CD-66-mAb on changes on TNF-{alpha} serum levels. Patients, methods: In 18 patients we measured TNF-{alpha} before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-{alpha} we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-{alpha} after conditioning with {sup 188}Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 {+-} 6.6 pg/ml) and chemotherapy (10.8 {+-} 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with {sup 188}Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-{alpha}. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

  18. Affinity of hydroxyapatite by radionuclides parent/child in {sup 188}Re/{sup 188}W generator for radiotherapy; Afinidad de la hidroxiapatita por los radionuclidos padre/hijo en el generador {sup 188}Re/{sup 188}W para radioterapia

    Energy Technology Data Exchange (ETDEWEB)

    Carrera D, A. A. [Universidad Autonoma de Zacatecas, Unidad Academica de Ciencias Quimicas, Campus Universitario Siglo XXI, Ejido La Escondida, Carretera a Guadalajara Km. 6 (Mexico); Badillo A, V. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela 98068, Zacatecas (Mexico); Badillo A, V. E.; Monroy G, F. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)], e-mail: ana_carrera7@hotmail.com

    2009-10-15

    To assess the feasibility of using apatites as matrices of {sup 188}W/{sup 188}Re generator is essential to obtain the distribution coefficients as much of parent radionuclide as child radionuclide in apatite, that is to say to know their affinity for the solid. It was selected the mineral species more representative as adsorbent, the hydroxyapatite Ca{sub 10} (PO{sub 4}){sub 6}(OH){sub 2} it is known for its great capacity of ions retention and by presenting a large affinity for anionic species in their surface. In this paper we use a synthetic hydroxyapatite marketed by Bio-Rad. This paper presents the preliminary results regarding the affinity of hydroxyapatite for the anionic species tungstates (WO{sub 4}{sup 2-}) and perrhenates (ReO{sub 4}{sup -} in EDTA, as background electrolyte expressed as distribution coefficients between two immiscible phases obtained with the help of radioactive tracers {sup 187}W and {sup 188}Re respectively. The retention measures of these ions, traces show that Bio-Gel hydroxyapatite presents moderate values of distribution coefficients for anionic species of W(Vi) in EDTA 0.01 mol/L that are in the range p H 5 to 6.5; the parent radionuclide of generator {sup 188}Re/{sup 188}W is fixed but not enough to consider it a good absorbent. By contrast, the fixation of perrhenate ions is virtually wiped as may be easily removed from a hydroxyapatite column packed with a saline solution. The influence of this saline solution in the removal of perrhenate ions is null practically. (Author)

  19. Development of activity standard for {sup 90}Y microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Mo, L. [Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234 (Australia) and Institute of Medical Physics, University of Sydney, NSW 2006 (Australia)]. E-mail: lmx@ansto.gov.au; Avci, B. [SIRTeX Medical Limited, Unit F6 Parkview, 16 Mars Road, Lane Cove, NSW 2066 (Australia); James, D. [SIRTeX Medical Limited, Unit F6 Parkview, 16 Mars Road, Lane Cove, NSW 2066 (Australia); Simpson, B. [CSIR National Metrology Laboratory, 15 Lower Hope Road, Rosebank, Cape Town 7700 (South Africa); Van Wyngaardt, W.M. [CSIR National Metrology Laboratory, 15 Lower Hope Road, Rosebank, Cape Town 7700 (South Africa); Cessna, J.T. [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Baldock, C. [Institute of Medical Physics, University of Sydney, NSW 2006 (Australia)

    2005-08-01

    {sup 90}Y microspheres are important therapeutic radiopharmaceuticals used in the treatment of liver cancer through a process known as selective internal radiation therapy. SIR-spheres[reg] is a radiopharmaceutical product that is comprised of {sup 90}Y microspheres suspended in sterile, pyrogen-free water for injection into patients. It is necessary to establish for the SIR-spheres[reg] production the capability of accurately measuring the activity of this product to a traceable national measurement standard. An activity standard for SIR-spheres[reg] was developed from a standard for {sup 90}Y solution, employing a highly quantifiable chemical digestion process. Calibration factors for the manufacturer's ionisation chambers were determined for 1 and 5 ml of the SIR-spheres[reg] product placed in Wheaton vials, for both 34% and 44% of {sup 90}Y microsphere concentration.

  20. Calculus of spatial distribution of absorbed dose to cellular level by Monte Carlo simulation for a radio-labelled peptide with {sup 188}Re and with nuclear internalization : preliminary results; Calculo de la distribucion espacial de dosis absorbida a nivel celular por simulacion Monte Carlo para un peptido radiomarcado con {sup 188}Re y con internalizacion nuclear : resultados preliminares

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E. L. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Santos C, C. L. [Universidad Autonoma del Estado de Mexico, Paseo Tollocan y Jesus Carranza, Toluca 50120, Estado de Mexico (Mexico)], e-mail: leticia.rojas@inin.gob.mx

    2009-10-15

    The {sup 188}Re is a radionuclide of radiation gamma emitter, useful in obtaining of gamma-graphic images, but it is also emitter of beta radiations and Auger electrons. A bio-molecule directed to a specific receptor of a cancer cell labeled with a emitter radionuclide of beta particles and Auger electrons, as the {sup 188}Re-Tat-Bombesin, it has the potential to be used in radiotherapy of molecular targets for its capacity to penetrate to cellular nucleus. In this system, the radiation dose is distributed in way located at microscopic levels in sub cellular specific places, where Auger emissions contributes of significant way in absorbed dose. The cellular dosimetry is realized in most of cases, using analytic or semi analytical methods, for example the cellular MIRD methodology. However, it is required to complement these calculations simulating the electrons transport and considering experimental bio kinetics data. Therefore, in this work preliminary results are presented of dosimetric calculation to sub cellular level for {sup 188}Re-Tat-Bombesin by Monte Carlo simulation, using the 2008 version of PENELOPE: PENEASY code. The spatial distribution of absorbed dose in membrane, cytoplasm and nucleus, was calculated with geometry of a cell of 10 {mu}m of diameter, a nucleus of 2 {mu}m of ratio and membrane of 0.2 {mu}m of thickness, considering elementary constitution for each cellular compartment proposal in literature. The total number of disintegrations at sub cellular level was evaluated integrating the activity in function of time starting from experimental bio kinetics data in mamma cancer cells MDA-MB231. The preliminary results show that 46.4% of total disintegrations for unit of captured activity by cell occurs in nucleus, 38.4% in membrane and 15.2% in cytoplasm. The due absorbed dose to Auger electrons for 1 Bq of {sup 188}Re located in cellular membrane were respectively of 1.32E-1 and 1.43E-1 Gy in cytoplasm and nucleus. (Author)

  1. Out sourcing treatments by {sup 177}Lu-Dotatoc of multi metastatic digestive neuroendocrine tumors: experience of a endocrine tumor pluri-disciplinary consultation meeting; Externalisation des traitements par Lu177-Dotatoc des tumeurs neuro-endocrines digestives multimetastatiques: l'experience d'une RCP de tumeurs endocrines

    Energy Technology Data Exchange (ETDEWEB)

    Dierickx, L.O.; Zerdoud, S.; Brillouet, S.; Courbon, F. [Institut Claudius-Regaud (CLCC), 31 - Toulouse (France); Duffas, J.P.; Danjoux, M.; Buscail, L.; Otal, P.; Guimbaud, R. [CHU Rangueil, 31 - Toulouse (France); Caron, P. [CHU Larrey, 49 - Angers (France)

    2010-07-01

    {sup 177}lu-Dotatoc could be a significant progress for internal vectorized radiotherapy of metastatic endocrine tumors. This therapy modality is currently only available abroad. Since 2006, we give indication for some patients of ours we address in these foreign centers. The treatment organisation, the management abroad, and the reimbursement as well as the the responses and the toxicity of the treatment have been evaluated. Conclusions: The results of the treatments are consistent with literature. The externalization of the treatment is feasible, well accepted but heavy to hold. In addition, to our knowledge, on 7 centers in Europe, the costs of care ranged from 3000 to 12000 Euros / injection. (N.C.)

  2. Synovectomy of the knee with /sup 90/Y

    Energy Technology Data Exchange (ETDEWEB)

    Spooren, P.F.M.J.; Rasker, J.J.; Arens, R.P.J.H.

    1985-05-01

    In 33 patients with chronic arthritis of the knee, 48 knees were treated with an intra-articular injection of 5 mCi yttrium silicate /sup 90/Y. There were 27 patients with rheumatoid arthritis (RA) and 6 with osteoarthrosis (OA); the mean follow-up period was 33 months. At clinical investigation after 1 year, no signs of pain or swelling were found in 15 knees. In most cases, pain and swelling improved subjectively, with a mean duration of 11 months; in 20 knees, the improvement lasted more than 22 months. When radiographs showed severe destruction, /sup 90/Y treatment was unsuccessful, but an important new finding was that most patients with mild or moderate radiological abormalities appeared to have a long-lasting improvement. The result did not correlate with erythrocyte sedimentation rate (ESR), haemoglobin or Rose titre at the time of injection or at follow up, suggesting that the result of the treatment is more dependent on local factors than on the disease activity. The results of /sup 90/Y treatment in 6 OA knees with persistent swelling were promising regarding swelling, even in patients with moderate radiological abnormalities. The main side-effect was a sometimes painful swelling of the knee, which was always successfully treated with an intra-articular corticosteroid injection. In /sup 90/Y-treated knees, the incidence of unstable joints was not significantly higher than in non-treated knees. In conclusion, /sup 90/Y synovectomy may be a succesful treatment for patients older than 50 years with chronic arthritis of the knee due to RA and probably also OA, even when moderate radiological abnormalities are present.

  3. Study by Monte Carlo simulation of the absorbed dose in cells of breast cancer of the line MDA-MB231, due to sources of {sup 111}In, {sup 177}Lu and {sup 99m}Tc internalized in the nucleus. First results; Estudio por simulacion Monte Carlo de la dosis absorbida en celulas de cancer de seno de la linea MDA-MB231, debida a fuentes de {sup 11I}n, {sup 177}Lu y {sup 99m}Tc internalizadas en el nucleo. Primeros resultados

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E. L.; Perez A, M., E-mail: leticia.rojas@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2011-11-15

    The necessity to design innovative treatments and to diagnose the cancer early, has taken to investigate therapies at cellular and molecular level. The design of appropriate radio-molecules to these therapies makes necessary to characterize in way exhaustive radionuclides that they are of accessible production in our country and to study as distributing the dose at cellular level with bio-molecules glued them. In this context, was realized the present work. Using Monte Carlo simulation, the energy deposited in a geometric model of cells of breast cancer was obtained, MDA-MB231, due to different radionuclides. The energy deposited in the nucleus was evaluated, in the cytoplasm and in the membrane of the cell, using the simulation code Monte Carlo Penelope 2008. A punctual source was simulated in the center of the cell nucleus. In each case all the emissions of each radionuclide majors to 400 eV were simulated. The energies deposited by disintegration in the nucleus, cytoplasm, membrane of the cell and in a sphere of 2 cm surrounding the source (in eV) were: 4.30E3, 4.85E2, 1.07E2 and 3.29E4, correspondingly, for the {sup 111}In; 4.46E3, 3.76E3, 1.26E3 and 1.33E5 for the {sup 177}Lu and; 2.12E3, 2.58E2, 9.33E1 and 1.88E4 for the {sup 99m}Tc. We can conclude that if the union of these radionuclides happens to a compound that was internalized to the cell nucleus, the best for therapy at this level is the conjugate with the {sup 177}Lu, followed by that with {sup 111}In and in third place that with {sup 99m}Tc. (Author)

  4. 放射性核素188Re诱导人乳腺癌ER-75-30细胞的凋亡%Apoptosis of human breast cancer cell induced by radionuclide 188Re

    Institute of Scientific and Technical Information of China (English)

    邹保民; 段小艺; 胡国瑛

    2002-01-01

    目的研究放射性核素188铼(188Re)诱导乳腺癌 ER-75-30细胞凋亡及其与bcl-2和bax基因表达的关系. 方法应用光镜、电镜、流式细胞仪和免疫组化方法检测不同浓度 188Re作用于体外培养的乳腺癌ER-75-30细胞后,诱导细胞凋亡及bcl-2和bax基因表达情况。结果188Re以诱导乳腺癌ER-75-30细胞发生凋亡形态学变化,并且随着188Re浓度增大,凋谢亡率增加,bcl-2表达减弱,bax表达增强。结论188Re能诱导乳腺癌ER-75-30细胞凋谢亡且具有剂量和周期依赖性,bcl-2和bax基因在188Re诱导的细胞凋亡过程中具有重要作用。%AIM To study apoptosis of human breast cancer ER-75-30 cell induced by 188Re and expression of bcl-2 gene and bax gene. METHODS Light microscope, transmissional electron microscope, flow cytometer and immunohistochemical method were used to observed ER-75-30 cells apoptosis after expose to 188Re of different doses and expressing of bcl-2 and bax. RESULTS 188Re can induced ER-75-30 cell producing typical morphologic changes of apoptosis and with the rise of radiation dose, cell apoptosis rate increased, bcl-2 gene decreased and bax gene was enhanced. Cells were blocked in G2/M period. CONCLUSION Radionuclide 188Re can induce tumor cell apoptosis. This effect takes on dose-effect relation and cellcycle dependent. bcl-2 and bax gene play import part in the course.

  5. Dosimetric studies of anti-CD20 labeled with therapeutic radionuclides at IPEN/CNEN-SP

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, G.; Dias, C.R.B.R.; Osso Junior, J.A., E-mail: gracielabarrio@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2012-07-01

    Radioimmunotherapy (RIT) makes use of monoclonal antibodies (MAb) labeled with alpha/beta radionuclides for therapeutical purposes, leading to tumor irradiation and destruction, preserving the normal organs on the radiation excess. The therapeutic activity to be injected in a specific patient is based on information obtained in dosimetric studies. Beta emitting radionuclides such as {sup 131}I, {sup 188}Re, {sup 90}Y, {sup 177}Lu and {sup 166}Ho are useful for the development of therapeutic radiopharmaceuticals. Anti-CD20 (Rituximab) is a chimeric MAb directed against antigen surface CD20 on B-lymphocytes, used in non-Hodgkin lymphoma treatment (NHL). The association with beta radionuclides have shown greater therapeutic efficacy. Currently, two radiopharmaceuticals with Anti-CD20 for radioimmunotherapy have FDA approval for NHL treatment: {sup 131}I-AntiCD20 (Bexar) and {sup 90}Y-AntiCD20 (Zevalin). Techniques for the radiolabeling of {sup 188}Re-antiCD20 have been recently developed by IPEN-CNEN/SP in order to evaluate the clinical use of this radionuclide in particular. The use of {sup 188}Re (T{sub 1/2} 17h) produced by the decay of {sup 188}W (T{sub 1/2} 69d), from an {sup 188}W/{sup 188}Re generator system, has represented an alternative to RIT. Beyond high energy beta emission for therapy, {sup 188}Re also emits gamma rays (155keV) suitable for image. The aim of this new project is to compare the labeling of anti-CD20 with {sup 188}Re with the same MAb labeled with {sup 131}I, {sup 177}Lu, {sup 90}Y and even {sup 99m}Tc. The first step in this project is the review of the published data available concerning the labeling of this MAb with different radionuclides, along with data obtained at IPEN, taking into account labeling procedures, labeling yields, reaction time, level and kind of impurities and biodistribution studies. The pharmacokinetic code will be developed in Visual Studio.NET platform through VB.NET and C{sup ++} for biodistribution and dosimetric

  6. 90Y-edotreotide for metastatic carcinoid refractory to octreotide.

    Science.gov (United States)

    Bushnell, David L; O'Dorisio, Thomas M; O'Dorisio, M Sue; Menda, Yusuf; Hicks, Rodney J; Van Cutsem, Eric; Baulieu, Jean-Louis; Borson-Chazot, Francoise; Anthony, Lowell; Benson, Al B; Oberg, Kjell; Grossman, Ashley B; Connolly, Mary; Bouterfa, Hakim; Li, Yong; Kacena, Katherine A; LaFrance, Norman; Pauwels, Stanislas A

    2010-04-01

    Metastatic carcinoid is an incurable malignancy whose symptoms, such as diarrhea and flushing, can be debilitating and occasionally life-threatening. Although symptom relief is available with octreotide, the disease eventually becomes refractory to octreotide, leaving no proven treatment options. The goal of this study was to evaluate the clinical effect of using (90)Y-edotreotide to treat symptomatic patients with carcinoid tumors. Patients enrolled had metastatic carcinoid, at least one sign/symptom refractory to octreotide, and at least one measurable lesion. Study treatment consisted of three cycles of 4.4 GBq (120 mCi) (90)Y-edotreotide each, once every 6 weeks. Ninety patients were enrolled in the study. Using Southwest Oncology Group tumor response criteria, 67 (74.%) of 90 patients (95% CI, 65.4% to 83.4%) were objectively stable or responded. A statistically significant linear trend toward improvement was demonstrated across all 12 symptoms assessed. Median progression-free survival was significantly greater (P = .03) for the 38 patients who had durable diarrhea improvement than the 18 patients who did not (18.2 v 7.9 months, respectively). Adverse events (AEs) were reported in 96.7% (87 of 90) of patients. These AEs consisted primarily of reversible GI events (76 of 90), which could be caused in part by concomitant administration of amino acid solution given to reduce radiation exposure to the kidneys. There was one case each of grade 3 oliguria and grade 4 renal failure, each lasting 6 days. (90)Y-edotreotide treatment improved symptoms associated with malignant carcinoid among subjects with no treatment alternatives. Treatment was well-tolerated and had an acceptable expected AE profile.

  7. The use of 99mTc-HYNIC-TOC and 18F-FDG PET/CT in the evaluation of duodenal neuroendocrine tumor with atypical and extensive metastasis responding dramatically to a single fraction of PRRT with 177Lu-DOTATATE.

    Science.gov (United States)

    Basu, Sandip; Abhyankar, Amit

    2014-12-01

    This report describes a case of extensive diffuse bone marrow involvement with bilateral breast metastases from duodenal neuroendocrine tumor giving rise to a superscan-like appearance on somatostatin receptor-targeted (99m)Tc-hydrazinonicotinamide-TOC scintigraphy. The metastatic lesions demonstrated partial concordance with (18)F-FDG PET/CT findings, signifying varying tumor biology and heterogeneity among metastatic lesions in the same individual, as illustrated with a dual-tracer approach. There was a dramatic symptomatic and biochemical response and better health-related quality of life with a single fraction of peptide receptor radionuclide therapy with (177)Lu-DOTATATE, and radiologically there was stable disease at that point.

  8. Liver radioembolization with {sup 90}Y microspheres. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Bilbao, Jose Ignacio [Clinica Universidad de Navarra, Pamplona (Spain). Dept. de Radiologia; Reiser, Maximilian F. (ed.) [Universitaetsklinikum Muenchen Klinikum Grosshadern, Muenchen (Germany). Inst. fuer Klinische Radiologie

    2014-07-01

    New, up-to-date edition of the only book devoted specifically to the subject. Key basic information on how to use the procedure successfully in clinical practice. Detailed information on candidate selection, vascular anatomy, dosimetry, and treatment evaluation. Thorough summary of published results. This is the second edition of a very well received book devoted specifically to the treatment of liver tumors by radioembolization with {sup 90}Y microspheres. The success of the first edition was based on the provision of all the fundamental information required for successful use of this therapeutic modality in clinical practice. The new edition has been fully updated to cover the most recent advances and includes additional chapters on regulations and emerging trends. Detailed information is provided on the full range of relevant topics, including hepatic vascular anatomy (including variants), dosimetry, assessment of tumor response, and the results achieved using radioembolization alone and in combination with other treatments in patients with primary or metastatic disease. Complications and side-effects are also fully discussed. This book will prove immensely valuable for both beginners and practitioners.

  9. Hanford isotope project strategic business analysis yttrium-90 (Y-90)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    The purpose of this analysis is to address the short-term direction for the Hanford yttrium-90 (Y-90) project. Hanford is the sole DOE producer of Y-90, and is the largest repository for its source in this country. The production of Y-90 is part of the DOE Isotope Production and Distribution (IP and D) mission. The Y-90 is ``milked`` from strontium-90 (Sr-90), a byproduct of the previous Hanford missions. The use of Sr-90 to produce Y-90 could help reduce the amount of waste material processed and the related costs incurred by the clean-up mission, while providing medical and economic benefits. The cost of producing Y-90 is being subsidized by DOE-IP and D due to its use for research, and resultant low production level. It is possible that the sales of Y-90 could produce full cost recovery within two to three years, at two curies per week. Preliminary projections place the demand at between 20,000 and 50,000 curies per year within the next ten years, assuming FDA approval of one or more of the current therapies now in clinical trials. This level of production would incentivize private firms to commercialize the operation, and allow the government to recover some of its sunk costs. There are a number of potential barriers to the success of the Y-90 project, outside the control of the Hanford Site. The key issues include: efficacy, Food and Drug Administration (FDA) approval and medical community acceptance. There are at least three other sources for Y-90 available to the US users, but they appear to have limited resources to produce the isotope. Several companies have communicated interest in entering into agreements with Hanford for the processing and distribution of Y-90, including some of the major pharmaceutical firms in this country.

  10. One column operation for (90)Sr/(90)Y separation by using a functionalized-silica.

    Science.gov (United States)

    Lee, Jun Sig; Park, Ul-Jae; Son, Kwang-Jae; Han, Hyon-Soo

    2009-01-01

    Organo-ceramic hybrid materials have been developed as the separation media for a (90)Sr/(90)Y generator system. Currently available (90)Y is generally extracted from a mother solution by a solvent extraction or a successive column operation. Both processes are successfully applied to produce (90)Y with a high quality standard. However, such processes are highly dependent on what kind of extracting materials are employed. Hence, some of the previously developed technologies are not adequate for a (90)Y production because of a waste generation or leaching of radiolytic end-products from the extracting materials. In this study, high performance organo-ceramic hybrid materials have been applied for the extraction of (90)Y. The hybrid materials have properties of both a ceramic and a solvent extractant by molecularly implanting the extracting molecules on to the ceramic surfaces. In this study, organo-phosphorus functionalized hybrid materials are synthesized and tested as the separation media for the (90)Y/(90)Sr generator system. An adsorptive extraction with a small Sep-Pak type column can recover more than 92% of (90)Y with a contamination ratio of (90)Sr/(90)Y=1.2x10(-5) from the mother solution and 70% with 5x10(-7).

  11. Evaluation Study for the Production of the Medical Isotope ^90Y, using a Cyclotron

    Science.gov (United States)

    Necsoiu, D.; Morgan, I. L.; Hupf, Homer; Armbruster, J.; Boyce, D.; El Bouanani, M.; McDaniel, F. D.

    2000-10-01

    The use of radioisotopes in therapy, medical imaging and laboratory tests is well-established worldwide. ^90Y is a very good therapeutic candidate for radioimmunotherapy applications. Traditionally, medical radioisotopes are produced using either nuclear reactors or proton accelerators. In this study, the medical isotope ^90Y has been produced using ^90Zr(n,p)^90Y nuclear reaction. Neutrons for the activation process were produced using ^natRh(p,xn) reaction with a 27 MeV proton beam from a cyclotron. Since ^90Y is a pure beta emitter, the gamma rays from the ^90Zr(n,2n)^89Zr reaction were used to quantify the incident neutron flux on the ^90Zr sample. Experimental results of the neutron production and ^90Y activity are presented.

  12. Clinical feasibility of {sup 90}Y digital PET/CT for imaging microsphere biodistribution following radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Chadwick L.; Binzel, Katherine; Zhang, Jun; Knopp, Michael V. [The Ohio State University Wexner Medical Center, Wright Center of Innovation in Biomedical Imaging, Department of Radiology, Columbus, OH (United States); Wuthrick, Evan J. [The Ohio State University Wexner Medical Center, Department of Radiation Oncology, Columbus, OH (United States)

    2017-07-15

    The purpose of this study was to evaluate the clinical feasibility of next generation solid-state digital photon counting PET/CT (dPET/CT) technology and imaging findings in patients following {sup 90}Y microsphere radioembolization in comparison with standard of care (SOC) bremsstrahlung SPECT/CT (bSPECT/CT). Five patients underwent SOC {sup 90}Y bremsstrahlung imaging immediately following routine radioembolization with 3.5 ± 1.7 GBq of {sup 90}Y-labeled glass microspheres. All patients also underwent dPET/CT imaging at 29 ± 11 h following radioembolization. Matched pairs comparison was used to compare image quality, image contrast and {sup 90}Y biodistribution between dPET/CT and bSPECT/CT images. Volumetric assessments of {sup 90}Y activity using different isocontour thresholds on dPET/CT and bSPECT/CT images were also compared. Digital PET/CT consistently provided better visual image quality and {sup 90}Y-to-background image contrast while depicting {sup 90}Y biodistribution than bSPECT/CT. Isocontour volumetric assessment using a 1% threshold precisely outlined {sup 90}Y activity and the treatment volume on dPET/CT images, whereas a more restrictive 20% threshold on bSPECT/CT images was needed to obtain comparable treatment volumes. The use of a less restrictive 10% threshold isocontour on bSPECT/CT images grossly overestimated the treatment volume when compared with the 1% threshold on dPET/CT images. Digital PET/CT is clinically feasible for the assessment of {sup 90}Y microsphere biodistribution following radioembolization, and provides better visual image quality and image contrast than routine bSPECT/CT with comparable acquisition times. With further optimization and clinical validation, dPET technology may allow faster and more accurate imaging-based assessment of {sup 90}Y microsphere biodistribution. (orig.)

  13. SPECT/CT 90Y-Bremsstrahlung images for dosimetry during therapy

    OpenAIRE

    Fabbri, C.; Sarti, G.; Agostini, M; Di Dia, A; Paganelli, G

    2008-01-01

    Background: the characteristics of 90Y, suitable for therapy, are denoted by the lack of γ-emission. Alternative methods, using analogues labelled with 111In or 86Y, are generally applied to image 90Y-conjugates, with some inevitable drawbacks. New generation SPECT/CT image systems offer improved Bremsstrahlung images. The intent of this brief communication is to show that high quality 90Y-Bremsstrahlung SPECT-CT images can be obtained, allowing the biodistribution of pure β-emitter therapeut...

  14. Therapy with {sup 90}Y microspheres: radiation protection in new medical therapies; Terapia con microesferas de {sup 90}Y: proteccion radiologica en nuevas terapias medicas

    Energy Technology Data Exchange (ETDEWEB)

    Rojo, Ana; Puerta, Nancy, E-mail: arojo@arn.gob.ar [Autoridad Regulatoria Nuclear (ARN), Buenos Aires (Argentina)

    2013-07-01

    Primary liver cancer is one of the most frequent in the world and with a low cure rate. Radioembolization using 90y spheres is a promising treatment of this pathology and involves the percutaneous vascular application of radioisotope-labeled the order of Micron size particles. The advantages of this technique include the permit administered high doses of radiation to small volumes with low relative toxicity, offer the possibility of treating all the liver including microscopic tumors, and finally, the feasibility of combined with other therapies. Radiation protection in new medical therapies requires justification and optimization, as requirements for their implementation. The application of the principle of optimization in the context of the protection of the patient must be the minimum that it can be reasonably reached compatible with the required doses of treatment dose to healthy tissue. With {sup 90}Y microspheres therapy this optimization applies to the activity of 90y which is administered to the patient, and estimation methods are postulated. in this work are analyzed comparatively these methods, described the early physicists, equations and the limitations of each. Finally, it is concluded that the optimal method to be implemented for the evaluation of the activity of {sup 90}Y manage must be based in a voxel dosimetric model specific for each patient, however, the partitional method may be a good alternative if you don't have the tools to apply the method.

  15. {sup 90}Sr/{sup 90}Y prostatic hyperplasia applicators and its clinical effects

    Energy Technology Data Exchange (ETDEWEB)

    Shanyu Cai [Academia Sinica, Beijing, BJ (China). Inst. of Atomic Energy; Zhi Li; Feng Chen

    1996-10-01

    Several main techniques for the treatment of benign prostatic hyperplasia (BPH) are reviewed simply in this paper. A novel technique of {sup 90}Sr/{sup 90}Y intracavitary therapy is described in detail. In recent years, two different kinds of {sup 90}Sr/{sup 90}Y prostatic hyperplasia applicators including `urethra-type` and `rectum-type` have been developed. The hypertrophic prostate gland can be irradiated by {sup 90}Sr/{sup 90}Y ({beta}) rays through the wall of urethra or rectum. Based on the animal experiments, a thousand cases of BPH have been observed respectively at ten hospitals since 1992. The clinical application indicate that the {sup 90}Sr/{sup 90}Y intracavitary applicator provides a safe, effective, reliable, and non-invasive method in curing BPH. In addition, it is apt for the high risk patients and costs of treatment are low. (author)

  16. Labeling of NGR Peptide With 188Re and Its Biodistribution and SPECT Imaging in Tumor-bearing Nude Mice%NGR短肽的188Re标记及其在荷瘤裸鼠体内的生物分布和SPECT显像

    Institute of Scientific and Technical Information of China (English)

    锁耀宇; 杨卫东; 马晓伟; 汪静

    2011-01-01

    采用188Re标记含有天冬酰胺、甘氨酸、精氨酸(Asn-Gly-Arg,NGR)序列的肿瘤血管靶向性短肽,得到188Re-NGR,观察了188Re-NGR在荷HepG2肝癌细胞严重联合免疫缺陷(Severe Combined Immunodeficiency,SCID)裸鼠肿瘤模型中的生物分布,并对其进行了SPECT显像.结果显示,188Re-NGR的标记率>85%,放化纯度>90%.188Re-NGR在肿瘤模型鼠体内的生物分布显示,注射188Re-NGR后12 h,肿瘤放射性摄取达最高,为(4.62±0.71)%ID/g,24 h时仍有(2.01±0.38)%ID/g,说明标记物在肿瘤内停留时间较长;竞争性抑制组中,12 h肿瘤放射性摄取为(1.43±0.61)%ID/g,明显低于实验组.肿瘤与肌肉组织的放射性摄取比(T/NT)12 h为4.76.注射后1 h肿瘤可显像,4~8 h显像逐渐清晰,12 h时更为清晰.以上结果提示,188Re-NGR具有良好的肿瘤血管靶向性.%To evaluate its radiochemical characteristics, biodistribution and imaging for nude mice bearing HepG2, 188Re-NGR was prepared directly with 2-mercapto-ethanol as reductant and sodium gluconate as middle ligand. The labeling yield of 188 Re-NGR was more than 85%, and the radiochemical purity (RCP) was more than 90%. In vivo, 188Re-NGR can specifically bind with tumor. The tumor uptake was (2.84±0.51)%ID/g at 1 h after injection, the uptake was(4. 62±0. 71)%ID/g at 12 h and remains (2.01±0.38)%ID/g for 24 h, the contrl group was (1.43±0.61)%ID/g. The ratio of tumor to muscle was 4.76 at 12 h. The xenografted tumor became visible at 1 h and was the most clearly at 12 h. The results showed that NGR had the function of good targeting.

  17. Radioembolization and the dynamic role of 90Y PET/CT

    Directory of Open Access Journals (Sweden)

    Alexander S Pasciak

    2014-02-01

    Full Text Available Before the advent of tomographic imaging, it was postulated that decay of 90Y to the 0+ excited state of 90Zr may result in emission of a positron-electron pair. While the branching ratio for pair production is small (~32x10-6, PET has been successfully used to image 90Y in numerous recent patient and phantom studies. 90Y PET imaging has been performed on a variety of PET/CT systems, with and without time-of-flight (TOF and/or resolution recovery capabilities as well as on both BGO and L(YSO based scanners. On all systems, resolution and contrast superior to bremsstrahlung SPECT has been reported. The intrinsic radioactivity present in L(YSO-based PET scanners is a potential limitation associated with accurate quantification of 90Y. However, intrinsic radioactivity has been shown to have a negligible effect at the high activity concentrations common in 90Y radioembolization. Accurate quantification is possible on a variety of PET scanner models, with or without TOF, although TOF improves accuracy at lower activity concentrations. Quantitative 90Y PET images can be transformed into 3D maps of absorbed dose based on the premise that the 90Y activity distribution does not change after infusion. This transformation has been accomplished primarily with the use of 3D dose point-kernel convolution. From a clinical standpoint, 90Y PET provides a superior post-infusion evaluation of treatment technical success owing to its improved resolution. Absorbed dose maps generated from quantitative PET data can be used to predict treatment efficacy and manage patient follow-up. For patients who receive multiple treatments, this information can also be used to provide patient-specific treatment planning for successive therapies, potentially improving response. The broad utilization of 90Y PET has the potential to provide a wealth of dose-response information, which may lead to development of improved radioembolization treatment-planning models in the future.

  18. Rapid 90Sr/90Y determination in water samples using a sequential injection method

    Science.gov (United States)

    Mateos; Gomez; Garcias; Casas; Cerda

    2000-07-01

    We have developed a semiautomatic procedure based on a sequential injection method for 90Sr/90Y determination that allows their radiochemical separation in about 30 min. The method has been tested using 90Sr/90Y solutions with activities lower than 12 Bq. The source is eluted in a pH = 6.5 medium through a MnO2-impregnated cotton filter, where 9OY is preconcentrated in preference by adsorption. 90Y is extracted from the column with hydroxylamine, some 90Sr in the leached solution has also been found. After the radiochemical separation, the total beta-activity of the leached solution has been determined using a low background alpha-beta proportional counter and, assuming the presence of 90Sr and 90Y at t = 0, the solution of the Bateman equations allows the initial concentration of both isotopes to be obtained. We have verified that the addition of some ions usually found in water samples (Cl-, HCO3-, NO3-, SO4(2-), Ca2+, Mg2+) does not interfere with the yield of the radiochemical process, (90 +/- 10)%. The method has been applied to 90Sr/90Y determination in mineral waters, and even in thermal waters, where the salt concentration can be about 3500 mg/l, the radiochemical yield remains greater than 80%.

  19. {sup 90}Y-oxine-ethiodol, a potential radiopharmaceutical for the treatment of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu Junfeng; Haefeli, U.O. E-mail: hafeliu@ccf.org; Sands, Mark; Dong Yonghua

    2003-05-01

    Ethiodol (or lipiodol) is selectively retained in hepatocellular carcinoma and is used as a vehicle to deliver radioactive agents following intraarterial hepatic infusion. We prepared the lipophilic complex {sup 90}Y-oxine with a radiolabeling efficiency of 97.6{+-}1.1%. After extraction into ethiodol, a stability test in serum at 37 deg. C showed that 87.8% of the {sup 90}Y remained ethiodol-bound for 7 days. Bremsstrahlung imaging of a rabbit for 48 h confirmed that the homogeneous mixture of radiolabeled {sup 90}Y-oxine and ethiodol stayed in the targeted liver lobe. This radiopharmaceutical is thus a potential candidate for the treatment of non-resectable liver cancer.

  20. Portable {sup 90}SR/{sup 90}Y prostatic hyperplasia applicators

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Shanyu; Tang, Kejian; Zhou, Changling [China Institute of Atomic Energy (China); Li, Zhi [Zhelimumen Hospital (China)

    1998-07-01

    In order to seek a new method of curing the benign prostatic hyperplasia (BPH), two different kinds of {sup 9} {sup 0}Sr/9{sup 0}Y intracavity applicators, including a 'urethra-type' and a 'rectum-type', have been developed in China since 1991. The structural design and radiation characteristics of the {sup 90}Sr/{sup 90}Y prostatic hyperplasia applicator are given in this paper. The hypertrophic prostate gland can be irradiated through the wall of the urethra or rectum by {sup 90}Sr/{sup 90}Y beta rays and small quantity of bremsstrahlung radiation from the applicator. Clinical tests indicate that the {sup 90}Sr/{sup 90}Y prostatic hyperplasia applicators provide a safe, effective, non-invasive and economical therapeutic method for BPH. It is especially applicable for old and high-risk patients. (author)

  1. A dosimetry evaluation of 90y-stent implantation in intracoronary radiation treatment

    Directory of Open Access Journals (Sweden)

    Karimian Alireza

    2013-01-01

    Full Text Available Ionizing particles have been used for the treatment of atherosclerosis. Internal irradiation is commonly carried out by means of several methods (catheter-based systems, radioactive stents or balloons to reduce the probability of restenosis. 90Y, due to some of its characteristics, is an appropriate radioisotope for intravascular brachytherapy. However, since there are some critical tissues in the vicinity of the heart like the breast and lymph nodes, it is necessary to perform a dosimetry calculation around the artery under radiotherapy to justify the treatment method. In this study, a 3-D dose distribution was obtained for the coronary vessel and its surrounding tissues for a standard 90Y stent in a MCNPX program. The results were compared with other investigations on restenosis prevention using 90Y-coated stents. The calculations represented a 28-day cumulative dose between 1230 cGy and 2400 cGy at 0.1 mm from the stent surface, while this quantity was about 23.8 cGy at 8.5 mm from the stent surface. An assessment of the dose equivalent and effective dose was also performed at r = 8.5 mm for the mentioned surrounding tissues which may be located in the area, based on the latest changes in ICRP recommendations. Additionally, the dose equivalent calculated within the treatment period for these organs was compared with published dosimetry data for 90Sr/90Y seed sources in order to evaluate radiation protection concerns about these two radiotherapy methods. It has been found that, depending on stent parameters, 90Y stent implantation might increase the unfavorable side effects for the patient, but to a much lesser degree than the other methods.

  2. Same-day {sup 90}Y radioembolization: implementing a new treatment paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Gabr, Ahmed; Kallini, Joseph Ralph; Gates, Vanessa L.; Hickey, Ryan; Desai, Kush; Thornburg, Bartley; Marshall, Karen; Salzig, Krystina; Williams, Melissa; Del Castillo, Carlene; Hohlastos, Elias; Lewandowski, Robert J. [Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Kulik, Laura; Ganger, Daniel [Northwestern University, Department of Medicine, Division of Hepatology, Chicago, IL (United States); Baker, Talia [Northwestern University, Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Chicago, IL (United States); Salem, Riad [Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Northwestern University, Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Chicago, IL (United States); Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Department of Medicine, Division of Hematology and Oncology, Chicago, IL (United States)

    2016-12-15

    To assess the feasibility of conducting pretreatment mesenteric angiography, coil embolization, {sup 99m}Tc macroaggregated albumin ({sup 99m}Tc-MAA) scintigraphy, and {sup 90}Y radioembolization treatment in a single, same-day, combined outpatient encounter. This was a retrospective study of 78 patients treated during the period 2008 - 2015 who were managed in a single outpatient encounter under the guidance of the Interventional Radiology Department and The Nuclear Medicine Department. Pretreatment planning was performed by reviewing baseline imaging and estimated perfused liver volume bearing the tumor. The region of interest was estimated using 3-D software; this value was used for dosimetry planning. Maximum lung shunting fractions of 10 % for hepatocellular carcinoma and 5 % for liver metastases were assumed. Subsequently, hepatic angiography and {sup 99m}Tc-MAA scintigraphy were performed followed by {sup 90}Y treatment in one outpatient encounter. Total in-room procedure time was recorded. All patients underwent same-day angiography, {sup 99m}Tc-MAA scintigraphy and {sup 90}Y radioembolization. Of the 78 patients, 16 received multiple segmental treatments to both lobes, 44 received treatment to the right lobe, and 18 received treatment to the left lobe. The median dose was 106 Gy. The median number of {sup 90}Y vials needed was two (range one to six). The median in-room time was 160 min (75 - 250 min). The residential status of the patients was as follows, 18 % (14/78) were local residents, 55 % (43/78) traveled from outside the city limits, 18 % (14/78) were from out-of-state, and 9 % (7/78) were resident abroad. Of the 78 patients, 61 (77 %) had hepatocellular carcinoma, and 17 (22 %) had liver metastases. The median lung dose was 3.5 Gy. This study demonstrated the feasibility of same-day {sup 90}Y evaluation and treatment while maintaining the principles of safe and effective {sup 90}Y infusion including tumoricidal dosimetry (lobar, segmentectomy

  3. Comparison of (90)Y activity measurements in nuclear medicine in Germany.

    Science.gov (United States)

    Kossert, Karsten; Bokeloh, Karen; Ehlers, Marion; Nähle, Ole; Scheibe, Olaf; Schwarz, Uwe; Thieme, Klaus

    2016-03-01

    In 2014, PTB and the company Eckert & Ziegler organized a national comparison exercise to determine the activity of a (90)Y solution. One aim of the comparison was to assess the measurement capability of hospitals and medical practices in Germany. P6-type vials were filled with aliquots of a radioactive (90)Y solution and then sent to 19 participants who were asked to measure the activity in the ampoules as well as in their own standard geometry using syringes. Most of the submitted results have a deviation of less than ±10% from the PTB reference activity when measured in the P6-type vials. The spread is somewhat larger when measured in a syringe geometry. The comparison revealed that some participants have difficulties in applying decay corrections and only a few participants were capable of estimating realistic measurement uncertainties.

  4. Disproof of solar influence on the decay rates of 90Sr/90Y

    CERN Document Server

    Kossert, Karsten

    2014-01-01

    A custom-built liquid scintillation counter was used for long-term measurements of 90Sr/90Y sources. The detector system is equipped with an automated sample changer and three photomultiplier tubes, which makes the application of the triple-to-double coincidence ratio (TDCR) method possible. After decay correction, the measured decay rates were found to be stable and no annual oscillation could be observed. Thus, the findings of this work are in strong contradiction to those of Parkhomov [1] who reported on annual oscillations when measuring 90Sr/90Y with a Geiger-M\\"uller counter. Sturrock et al. [2] carried out a more detailed analysis of the experimental data from Parkhomov and claimed to have found correlations between the decay rates and processes inside the Sun. These findings are questionable, since they are based on inappropriate experimental data as is demonstrated in this work. A frequency analysis of our activity data does not show any significant periodicity.

  5. Radiopharmaceutical development based on human blood albumin microspheres and 90Y

    Science.gov (United States)

    Petriev, V. M.; Vlasova, O. P.; Postnov, A. A.; Epstein, N. B.

    2017-01-01

    New radiopharmaceutial (RP) based on human serum albumin microspheres (MSA) and 90Y was developed for treatment of liver cancer. The optimized synthesis using chelation resulted in approximately 80% yield with high specific activity. The RP developed was tested in mice with inoculated sarcoma-37. In two weeks the tumor size reduced by 43% after the treatment with the dose of 500 μCi injected into the tumor site.

  6. Efficiency calibration of a liquid scintillation counter for {sup 90}Y Cherenkov counting

    Energy Technology Data Exchange (ETDEWEB)

    Vaca, F. [Huelva Univ. (Spain). Dept. de Fisica Aplicada e Ingenieria Electrica; Manjon, G. [Departamento de Fisica Aplicada, E.T.S. de Arquitectura, Universidad de Sevilla, Av. Reina Mercedes, 2, E-41012 Sevilla (Spain); Garcia-Leon, M. [Departamento de Fisica Atomica, Molecular y Nuclear, Facultad de Fisica, Universidad de Sevilla, Av. Reina Mercedes, s/n. Apartado 1061, E-41080 Sevilla (Spain)

    1998-04-01

    In this paper a complete and self-consistent method for {sup 90}Sr determination in environmental samples is presented. It is based on the Cherenkov counting of {sup 90}Y with a conventional liquid scintillation counter. The effects of color quenching on the counting efficiency and background are carefully studied. A working curve is presented which allows to quantify the correction in the counting efficiency depending on the color quenching strength. (orig.). 6 refs.

  7. Peptide receptor radionuclide therapy with {sup 90}Y-DOTATOC in recurrent meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Bartolomei, Mirco; Bodei, Lisa; De Cicco, Concetta; Grana, Chiara Maria; Baio, Silvia Melania; Arico, Demetrio; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Botteri, Edoardo [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Radiometabolic Medicine Division, Meldola (Italy)

    2009-09-15

    Meningiomas are generally benign and in most cases surgery is curative. However, for high-grade histotypes or partially resected tumours, recurrence is fairly common. External beam radiation therapy (EBRT) is usually given in such cases but is not always effective. We assessed peptide receptor radionuclide therapy (PRRT) using {sup 90}Y-DOTATOC in a group of patients with meningioma recurring after standard treatments in all of whom somatostatin receptors were strongly expressed on meningioma cell surfaces. Twenty-nine patients with scintigraphically proven somatostatin subtype 2 receptor-positive meningiomas were enrolled: 14 had benign (grade I), 9 had atypical (grade II) and 6 had malignant (grade III) disease. Patients received intravenous {sup 90}Y-DOTATOC for 2-6 cycles for a cumulative dose in the range of 5-15 GBq. Clinical and neuroradiological evaluations were performed at baseline, during and after PRRT. The treatment was well tolerated in all patients. MRI 3 months after treatment completion showed disease stabilization in 19 of 29 patients (66%) and progressive disease in the remaining 10 (34%). Better results were obtained in patients with grade I meningioma than in those with grade II-III, with median time to progression (from beginning PRRT) of 61 months in the low-grade group and 13 months in the high-grade group. PRRT with {sup 90}Y-DOTATOC can interfere with the growth of meningiomas. The adjuvant role of this treatment, soon after surgery, especially in atypical and malignant histotypes, deserves further investigation. (orig.)

  8. A Comparison of Techniques for 90Y PET/CT Image-Based Dosimetry Following Radioembolization with Resin Microspheres

    Science.gov (United States)

    Pasciak, Alexander S.; Bourgeois, Austin C.; Bradley, Yong C.

    2014-01-01

    90Y PET/CT following radioembolization has recently been established as a viable diagnostic tool, capable of producing images that are both quantitative and have superior image quality than alternative 90Y imaging modalities. Because radioembolization is assumed to be a permanent implant, it is possible to convert quantitative 90Y PET image sets into data representative of spatial committed absorbed-dose. Multiple authors have performed this transformation using dose-point kernel (DPK) convolution to account for the transport of the high-energy 90Y β-particles. This article explores a technique called the Local Deposition Method (LDM), an alternative to DPK convolution for 90Y image-based dosimetry. The LDM assumes that the kinetic energy from each 90Y β-particle is deposited locally, within the voxel where the decay occurred. Using the combined analysis of phantoms scanned using 90Y PET/CT and ideal mathematical phantoms, an accuracy comparison of DPK convolution and the LDM has been performed. Based on the presented analysis, DPK convolution provides no detectible accuracy benefit over the LDM for 90Y PET-based dosimetry. For PET systems with 90Y resolution poorer than 3.25 mm at full-width and half-max using a small voxel size, the LDM may produce a dosimetric solution that is more accurate than DPK convolution under ideal conditions; however, image noise can obscure some of the perceived benefit. As voxel size increases and resolution decreases, differences between the LDM and DPK convolution are reduced. The LDM method of post-radioembolization dosimetry has the advantage of not requiring additional post-processing. The provided conversion factors can be used to determine committed absorbed-dose using conventional PET image analysis tools. The LDM is a recommended option for routine post-radioembolization 90Y dosimetry based on PET/CT imaging. PMID:24904832

  9. Utilization of a novel electrochemical {sup 90}Sr/{sup 90}Y generator for the preparation of {sup 90}Y-labeled RGD peptide dimer in clinically relevant dose

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sudipta; Chakravarty, Rubel; Pillai, Maroor Raghavan Ambikalmajan; Dash, Ashutosh [Bhabha Atomic Research Centre, Mumbai (India). Radiopharmaceuticals Div.; Sarma, Haladhar Dev [Bhabha Atomic Research Centre, Mumbai (India). Radiation Biology and Health Sciences Div.

    2014-09-01

    The work reported in this paper provides a systematic study towards the development of an optimized strategy for preparation of a clinically relevant dose of {sup 90}Y-labeled dimeric RGD peptide derivative, DOTA-E[c(RGDfK)]{sub 2} [DOTA-(RGD){sub 2}] for in vivo targeted therapy utilizing {sup 90}Y obtained from a novel electrochemical {sup 90}Sr/{sup 90}Y generator. The performance of the generator was evaluated to ensure its suitability for providing {sup 90}Y in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. {sup 90}Y-DOTA-(RGD){sub 2} was synthesized in high yield (86.2 ± 2.5%) and radiochemical purity (98.4 ± 0.5%) using clinically relevant dose (∝ 3.8 GBq) of {sup 90}Y. In vitro stability studies revealed that the radiolabeled conjugate retained its radiochemical purity in normal saline and human serum. Preliminary biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed that the preparation exhibited significant tumor uptake (5.30 ± 0.78% of injected activity at 30 min post-injection) with good tumor to background ratio. The optimized radiolabeling protocol seems to be an attractive strategy which is largely viewed as a springboard to realize scope of developing {sup 90}Y labeled cyclic RGD peptides for targeted therapy of tumors over-expressing integrin-α{sub ν}β{sub 3} receptors. (orig.)

  10. Comparative analysis of 11 different radioisotopes for palliative treatment of bone metastases by computational methods

    Energy Technology Data Exchange (ETDEWEB)

    Guerra Liberal, Francisco D. C., E-mail: meb12020@fe.up.pt, E-mail: adriana-tavares@msn.com; Tavares, Adriana Alexandre S., E-mail: meb12020@fe.up.pt, E-mail: adriana-tavares@msn.com; Tavares, João Manuel R. S., E-mail: tavares@fe.up.pt [Instituto de Engenharia Mecânica e Gestão Industrial, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, Porto 4200-465 (Portugal)

    2014-11-01

    Purpose: Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods. Methods: Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 ({sup 32}P), strontium-89 ({sup 89}Sr), yttrium-90 ({sup 90}Y ), tin-117 ({sup 117m}Sn), samarium-153 ({sup 153}Sm), holmium-166 ({sup 166}Ho), thulium-170 ({sup 170}Tm), lutetium-177 ({sup 177}Lu), rhenium-186 ({sup 186}Re), rhenium-188 ({sup 188}Re), and radium-223 ({sup 223}Ra). Results: {sup 223}Ra alpha particles, {sup 177}Lu beta minus particles, and {sup 170}Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by {sup 89}Sr and {sup 153}Sm, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than {sup 177}Lu beta minus particles and {sup 223}Ra alpha particles. Conclusions: {sup 223}Ra and {sup 177}Lu hold the highest potential for palliative treatment of bone metastases of all

  11. Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial.

    Science.gov (United States)

    Gulec, Seza A; Cohen, Steven J; Pennington, Kenneth L; Zuckier, Lionel S; Hauke, Ralph J; Horne, Heather; Wegener, William A; Teoh, Nick; Gold, David V; Sharkey, Robert M; Goldenberg, David M

    2011-06-15

    Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer. Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). (111)In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before (90)Y-hPAM4; otherwise, 20 patients received (90)Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with (90)Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated (90)Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer. ©2011 AACR.

  12. End-stage renal disease after treatment with {sup 90}Y-DOTATOC

    Energy Technology Data Exchange (ETDEWEB)

    Cybulla, M.; Weiner, S.M.; Otte, A. [Dept. of Internal Medicine, University Hospital Freiburg (Germany)

    2001-10-01

    DOTA-D-Phe{sup 1}-Tyr{sup 3}-octreotide (DOTATOC), a newly developed somatostatin analogue which can be stably labelled with the {beta}-emitter yttrium-90, can be used for receptor-mediated internal radiotherapy. A 78-year-old woman suffering from a carcinoid of the small intestine with multiple metastases in the liver as well as mesenteric and supraclavicular lymph node metastases was treated with this therapy after the disease had progressed under other chemotherapy options employed years previously. The patient received four single doses of {sup 90}Y-DOTATOC at 6-week intervals, yielding a cumulative dose of 9,620 MBq (5,659 MBq/m{sup 2}). Restaging revealed stable metastatic disease. Serum creatinine and urea nitrogen levels were within the normal range prior to starting and during DOTATOC therapy. However, 15 months after cessation of DOTATOC therapy, a progressive deterioration of renal function occurred, leading to end-stage renal disease. Urinalysis revealed a slight proteinuria of 700 mg/day without haematuria, leucocyturia or casts. There was no obvious risk factor for chronic renal insufficiency except DOTATOC therapy. However, it was not feasible to use kidney biopsy to prove the presence of radiation-induced nephritis. Intermittent haemodialysis was started as the creatinine clearance declined to below 10 ml/min. Diuresis was not affected. The presented case shows delayed renal insufficiency after a relatively low cumulative dose of {sup 90}Y-DOTATOC (5,659 MBq/m{sup 2}). This serious adverse event indicates that further studies are needed to evaluate which dose of {sup 90}Y-DOTATOC, under which renal protection regimen, will provide optimal management, balancing risks and benefits. (orig.)

  13. Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry

    Directory of Open Access Journals (Sweden)

    Justin Mikell

    2014-03-01

    Full Text Available Purpose: Dosimetry for 90Y microsphere therapies (YMT with Standard (SM and Partition (PM models provide only uniform dose estimates to tumor and liver. Our objective is to calculate tumor dose heterogeneity, known to effect response, using voxel-based dosimetry and investigate the limitations of SM and PM.Methods: Voxel-based dosimetry was performed on 17 YMT patients using Monte Carlo DOSXYZnrc. 90Y activity and tissue/density distributions were based on quantitative 90Y bremsstrahlung SPECT/CT. Tumors (n=31, liver, and treatment lobe/segments were segmented on diagnostic CT or MR. Dose volume histograms (DVH were created for tumors and normal liver. Bland-Altman analysis compared voxel-based mean absorbed doses to tumor and liver with SM and PM. Tumor and normal liver absorbed dose heterogeneity were investigated through metrics: integral uniformity (IU, D10/D90, COV. Correlations of heterogeneity with voxel-based mean doses and volumes were evaluated.Results: Heterogeneity metrics (mean ± 1σ for tumor dose were COV = 0.48 ± 0.28, D10/D90 = 4.7 ± 3.9, and IU = 0.8 ± 0.18. Heterogeneity metrics correlated with tumor volume (r > 0.58 but not tumor mean doses (r < 0.20. Voxel-based tumor mean doses correlated with PM (r = 0.84 but not SM (r = 0.08. Both yielded poor limits of agreement with of 83 ± 174 and -28 ± 181 Gy, respectively. Normal liver heterogeneity metrics (mean ± 1σ were COV = 0.83 ± 0.29, D10/D90 = 12 ± 15, and IU = 0.97 ± 0.03. Only D10/D90 (r = 0.49 correlated with mean normal liver absorbed dose. Voxel-based normal liver/lobe mean doses correlated with PM (r = 0.96, but had poor limits of agreement (26 ± 29 Gy.Conclusion: Tumor doses have high levels of heterogeneity that increase with volume but are independent of dose. Voxel-based DVH and dose heterogeneity metrics will promote accurate characterization of tumor response following YMT.--------------------------------------Cite this article as: Mikell J, Mourtada F

  14. Treatment of cystic craniopharyngioma with 90Y-Colloid. Four clinical cases.

    Science.gov (United States)

    Sabaté-Llobera, A; Rojas-Camacho, J G; Mora Salvadó, J; Acebes Martín, J J; Rodríguez-Gasén, A; Ramal Leiva, D; Martín-Comín, J

    2013-01-01

    Craniopharyngioma is a histologically benign and frequently cystic intracranial tumor. It may present aggressive behavior due to compression from nearby structures. Its therapeutic management is complicated because although surgery is the usual treatment of choice, it is not exempt of high morbidity and mortality and frequent tumor recurrence. In craniopharyngiomas with a significant cystic component,internal irradiation with radioactive isotopes is a therapeutic alternative to conventional treatments. We present the cases of four patients with cystic craniopharyngiomas who were treated with intracystic administration of 90Y-colloid, and their evolution after the treatment. Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

  15. PET optimization for improved assessment and accurate quantification of {sup 90}Y-microsphere biodistribution after radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Martí-Climent, Josep M., E-mail: jmmartic@unav.es; Prieto, Elena; Elosúa, César; Rodríguez-Fraile, Macarena; Domínguez-Prado, Inés; Vigil, Carmen; García-Velloso, María J.; Arbizu, Javier; Peñuelas, Iván; Richter, José A. [Nuclear Medicine Department, Clínica Universidad de Navarra, 36, Pío XII Avenue, 31008 Pamplona (Spain)

    2014-09-15

    Purpose: {sup 90}Y-microspheres are widely used for the radioembolization of metastatic liver cancer or hepatocellular carcinoma and there is a growing interest for imaging {sup 90}Y-microspheres with PET. The aim of this study is to evaluate the performance of a current generation PET/CT scanner for {sup 90}Y imaging and to optimize the PET protocol to improve the assessment and the quantification of {sup 90}Y-microsphere biodistribution after radioembolization. Methods: Data were acquired on a Biograph mCT-TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. Spatial resolution was measured with a{sup 90}Y point source. Sensitivity was evaluated using the NEMA 70 cm line source filled with {sup 90}Y. To evaluate the count rate performance, {sup 90}Y vials with activity ranging from 3.64 to 0.035 GBq were measured in the center of the field of view (CFOV). The energy spectrum was evaluated. Image quality with different reconstructions was studied using the Jaszczak phantom containing six hollow spheres (diameters: 31.3, 28.1, 21.8, 16.1, 13.3, and 10.5 mm), filled with a 207 kBq/ml {sup 90}Y concentration and a 5:1 sphere-to-background ratio. Acquisition time was adjusted to simulate the quality of a realistic clinical PET acquisition of a patient treated with SIR-Spheres{sup ®}. The developed methodology was applied to ten patients after SIR-Spheres{sup ®} treatment acquiring a 10 min per bed PET. Results: The energy spectrum showed the{sup 90}Y bremsstrahlung radiation. The {sup 90}Y transverse resolution, with filtered backprojection reconstruction, was 4.5 mm in the CFOV and degraded to 5.0 mm at 10 cm off-axis. {sup 90}Y absolute sensitivity was 0.40 kcps/MBq in the center of the field of view. Tendency of true and random rates as a function of the {sup 90}Y activity could be accurately described using linear and quadratic models, respectively. Phantom studies demonstrated that, due to low count statistics in {sup 90}Y PET

  16. 90Y-DOTA-CHS Microspheres for Live Radiomicrosphere Therapy: Preliminary In Vivo Lung Radiochemical Stability Studies

    Directory of Open Access Journals (Sweden)

    Alejandro Amor-Coarasa

    2014-01-01

    Full Text Available Chitosan (CHS is used to prepare microspheres of 31 ± 8 µm size. Surface modification with p-SCN-Bn-DOTA was performed. A maximum 90Y capacity was found to be 12.1 ± 4.4 µCi/particle. The best obtained labeling yield was 87.7 ± 0.6%. More than 90% in vitro stability was found. Particle in vitro degradation half-life in PBS was found to be greater than 21 days. In vivo studies with 90Y-DOTA-CHS showed more than 95% of the injected activity (decay corrected in the lungs 24 hours after tail vein administration. 90Y-DOTA-CHS in vivo label stability was superior to resin microspheres. The addition of p-SCN-Bn-DOTA served as a radioprotectant for bone marrow as the 5% 90Y released, during the first 24 hours, was quickly eliminated via urine.

  17. Time optimization of (90)Sr measurements: Sequential measurement of multiple samples during ingrowth of (90)Y.

    Science.gov (United States)

    Holmgren, Stina; Tovedal, Annika; Björnham, Oscar; Ramebäck, Henrik

    2016-04-01

    The aim of this paper is to contribute to a more rapid determination of a series of samples containing (90)Sr by making the Cherenkov measurement of the daughter nuclide (90)Y more time efficient. There are many instances when an optimization of the measurement method might be favorable, such as; situations requiring rapid results in order to make urgent decisions or, on the other hand, to maximize the throughput of samples in a limited available time span. In order to minimize the total analysis time, a mathematical model was developed which calculates the time of ingrowth as well as individual measurement times for n samples in a series. This work is focused on the measurement of (90)Y during ingrowth, after an initial chemical separation of strontium, in which it is assumed that no other radioactive strontium isotopes are present. By using a fixed minimum detectable activity (MDA) and iterating the measurement time for each consecutive sample the total analysis time will be less, compared to using the same measurement time for all samples. It was found that by optimization, the total analysis time for 10 samples can be decreased greatly, from 21h to 6.5h, when assuming a MDA of 1Bq/L and at a background count rate of approximately 0.8cpm.

  18. Occupational radiation exposure of medical staff performing {sup 90}Y-loaded microsphere radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Laffont, Sophie; Ardisson, Valerie; Lenoir, Laurence [Cancer Institute, Centre Eugene Marquis, Department of Nuclear Medicine, Rennes (France); Rolland, Yan; Rohou, Tanguy [Cancer Institute, Centre Eugene Marquis, Department of Interventional Radiology, Rennes (France); Edeline, Julien [University of Rennes 1, Rennes (France); Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Oncology, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Pracht, Marc; Sourd, Samuel Le [Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Oncology, Rennes (France); Lepareur, Nicolas [Cancer Institute, Centre Eugene Marquis, Department of Nuclear Medicine, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Garin, Etienne [Cancer Institute, Centre Eugene Marquis, Department of Nuclear Medicine, Rennes (France); University of Rennes 1, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France)

    2016-05-15

    Radioembolization of liver cancer with {sup 90}Y-loaded microspheres is increasingly used but data regarding hospital staff exposure are scarce. We evaluated the radiation exposure of medical staff while preparing and injecting {sup 90}Y-loaded glass and resin microspheres especially in view of the increasing use of these products. Exposure of the chest and finger of the radiopharmacist, nuclear medicine physician and interventional radiologist during preparation and injection of 78 glass microsphere preparations and 16 resin microsphere preparations was monitored. Electronic dosimeters were used to measure chest exposure and ring dosimeters were used to measure finger exposure. Chest exposure was very low for both products used (<10 μSv from preparation and injection). In our experience, finger exposure was significantly lower than the annual limit of 500 mSv for both products. With glass microspheres, the mean finger exposure was 13.7 ± 5.2 μSv/GBq for the radiopharmacist, and initially 17.9 ± 5.4 μSv/GBq for the nuclear medicine physician reducing to 13.97 ± 7.9 μSv/GBq with increasing experience. With resin microspheres, finger exposure was more significant: mean finger exposure for the radiopharmacist was 295.1 ± 271.9 μSv/GBq but with a reduction with increasing experience to 97.5 ± 35.2 μSv/GBq for the six most recent dose preparations. For administration of resin microspheres, the greatest mean finger exposure for the nuclear medicine physician (the most exposed operator) was 235.5 ± 156 μSv/GBq. Medical staff performing {sup 90}Y-loaded microsphere radioembolization procedures are exposed to safe levels of radiation. Exposure is lower than that from treatments using {sup 131}I-lipiodol. The lowest finger exposure is from glass microspheres. With resin microspheres finger exposure is acceptable but could be optimized in accordance with the ALARA principle, and especially in view of the increasing use of radioembolization. (orig.)

  19. Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

    Science.gov (United States)

    Wagner, Henry N; Wiseman, Gregory A; Marcus, Carol S; Nabi, Hani A; Nagle, Conrad E; Fink-Bennett, Darlene M; Lamonica, Dominick M; Conti, Peter S

    2002-02-01

    90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for handling body fluids are recommended for health care workers and patients and their family members after (90)Y-ibritumomab tiuxetan administration. In summary, (90)Y-ibritumomab tiuxetan introduces (90)Y into clinical practice and expands the role

  20. Long-term effect of /sup 90/Y pituitary implantation in acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Jadresic, A.; Jimenez, L.E.; Joplin, G.F.

    1987-01-01

    This report examines the long-term trends in GH levels and pituitary function in a group of 38 acromegalic patients who were selected insofar as we were able to follow them up for more than 10 years after a single dose /sup 90/Y interstitial pituitary irradiation as the sole treatment. Mean serum GH had fallen from 106 to 24 mIU/l within 3-6 months and then slowly declined to 4 mIU/l after 10 years. GH levels of less than or equal to 5 mIU/l during a 50 g oral glucose tolerance test were obtained in 8% of patients at 3-6 months and in 18% at 1 year, the cumulative percentage increasing to 53% at 10, and 76% at 14 years. The percentage of patients requiring hormone replacement therapy rose from nil pre-implant to 16% by 3-6 months, and then slowly increased to 39% by 14 years. Serial coned radiographs of the pituitary fossa were available for 32 patients. By 10 years, 16 showed thickening of the dorsum sellae and/or reduction of at least one diameter by 3 mm. Concerning symptoms, all 29 patients whose GH level fell to less than or equal to 5 mIU/l showed improvements, 22 becoming asymptomatic. Seven patients with lesser falls in GH levels (from a mean of 193 to a mean of 15 mIU/l) all improved, one becoming asymptomatic. Two showed no variation. These results show that /sup 90/Y pituitary implants have a cumulative effect over the years in inducting remission and hypopituitarism in acromegalic patients, the early decline in GH levels being swifter than from other forms of irradiation.

  1. Resin Versus Glass Microspheres for (90)Y Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma Using Pretreatment Partition Model Dosimetry.

    Science.gov (United States)

    Van Der Gucht, Axel; Jreige, Mario; Denys, Alban; Blanc-Durand, Paul; Boubaker, Ariane; Pomoni, Anastasia; Mitsakis, Periklis; Silva-Monteiro, Marina; Gnesin, Silvano; Lalonde, Marie Nicod; Duran, Rafael; Prior, John O; Schaefer, Niklaus

    2017-08-01

    The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with (90)Y transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD). Methods: We performed a retrospective analysis of prospectively collected data on 77 patients consecutively treated (mean age ± SD, 66.4 ± 12.2 y) for uHCC (36 uninodular, 5 multinodular, 36 diffuse) with (90)Y TARE (41 resin, 36 glass) using pretreatment PMD. Study endpoints were progression-free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier estimates. Several variables including Barcelona Clinic Liver Cancer (BCLC) staging system, tumor size, and serum α-fetoprotein (AFP) level were investigated using Cox proportional hazards regression. Results: The characteristics of 2 groups were comparable with regard to demographic data, comorbidities, Child-Pugh score, BCLC, serum AFP level, and (90)Y global administered activity. The median follow-up time was 7.7 mo (range, 0.4-50.1 mo). Relapse occurred in 44 patients (57%) at a median of 6 mo (range, 0.4-27.9 mo) after (90)Y TARE, and 41 patients (53%) died from tumor progression. Comparison between resin and glass microspheres revealed higher but not statistically significantly PFS and OS rates in the (90)Y resin group than the (90)Y glass group (resin PFS 6.1 mo [95% confidence interval CI, 4.7-7.4] and glass PFS 5 mo [95% CI, 0.9-9.2], P = 0.53; resin OS 7.7 mo [95% CI, 7.2-8.2] and glass OS 7 mo [95% CI 1.6-12.4], P = 0.77). No significant survival difference between both types of (90)Y microspheres was observed in any subgroups of patients with early/intermediate or advanced BCLC stages. Among the variables investigated, Cox analyses showed that only in the glass group, the BCLC staging system and the serum AFP level were associated with PFS (P = 0.04) and OS (P = 0.04). Tumor size was a prognostic factor without significant influence on PFS and OS after (90)Y TARE. Conclusion

  2. Inflammation-induced synergetic enhancement of nanoparticle treatments with DOXIL® and 90Y-Lactosome for orthotopic mammary tumor

    Science.gov (United States)

    Kurihara, Kensuke; Ueda, Motoki; Hara, Isao; Hara, Eri; Sano, Kohei; Makino, Akira; Ozeki, Eiichi; Yamamoto, Fumihiko; Saji, Hideo; Togashi, Kaori; Kimura, Shunsaku

    2016-05-01

    Polymeric micelles (Lactosome) in the size of 20-30 nm were labeled with radionuclides of 111In (111In-DOTA-Lactosome) for SPECT imaging and 90Y (90Y-DOTA-Lactosome) for β-ray irradiation for mammary tumor in mice. The tumor site at the femoral right leg grafted with 4T1 cells was clearly imaged at 24 h after the intravenous injection. Biodistribution revealed that the half-life time of 111In-DOTA-Lactosome was 11 h, which enabled the nanoparticle selectively accumulated in tumor site due to the enhanced permeability and retention (EPR) effect. The anti-tumor therapeutic effect of 90Y-DOTA-Lactosome was observed depending on the dose frequency and amount. Under the condition of the percutaneous ethanol injection treatment, the therapeutic effect of 90Y-DOTA-Lactosome was enhanced due to the super EPR effect. Owing to the super EPR effect, co-administration of 90Y-DOTA-Lactosome and DOXIL® inhibited the tumor growth during 15 days with their administrations.

  3. Radioembolization with {sup 90}Y-labeled microspheres. Post-therapeutic therapy validation with Bremsstrahlung-SPECT; Radioembolisation mit {sup 90}Y-markierten Mikrosphaeren. Posttherapeutische Therapievalidierung mit Bremsstrahlungs-SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Grosser, Oliver S. [Universitaetsklinikum Magdeburg A.oe.R. (Germany). Klinik fuer Radiologie und Nuklearmedizin; Medizinische Hochschule Hannover (Germany). Stabsstelle Strahlenschutz und Medizinische Physik; Nultsch, Madeleine; Laatz, Kathleen [Universitaetsklinikum Magdeburg A.oe.R. (Germany). Klinik fuer Radiologie und Nuklearmedizin] [and others

    2011-07-01

    During the last years angiographic Selective Internal Radiotherapy (SIRT) with {sup 90}Y-labelled microspheres has become a common technique for the local-ablative treatment of cancer patients. SIRT is a palliative therapy concept for the treatment of liver malignancies. As a result of {sup 90}Y-decay as {beta}{sup -}-emitter without a concomitant gamma radiation, Bremsstrahlung imaging is needed to validate the distribution achieved by radioembolisation. This article demonstrates the method of imaging through phantom measurement and shows the advantages of post-therapeutic tomography by means of a patient study. Approaches for further optimization of Bremsstrahlung imaging are discussed. (orig.)

  4. Three dosimetry models of lipoma arborescens treated by {sup 90}Y synovectomy

    Energy Technology Data Exchange (ETDEWEB)

    O’Doherty, Jim, E-mail: jim.odoherty@kcl.ac.uk [Department of Medical Physics-Nuclear Medicine, Royal Surrey County Hospital, Guildford GU2 7XX, United Kingdom and Division of Imaging Sciences, PET Imaging Centre at St. Thomas’ Hospital, King' s College London, London SE1 7EH (United Kingdom); Clauss, Ralf [Department of Nuclear Medicine, Royal Surrey County Hospital, Guildford GU2 7XX (United Kingdom); Scuffham, James [Department of Medical Physics-Nuclear Medicine, Royal Surrey County Hospital, Guildford GU2 7XX (United Kingdom); Khan, Aman [Department of Rheumatology, Royal Surrey County Hospital, Guildford GU2 7XX (United Kingdom); Petitguillaume, Alice; Desbrée, Aurélie [Service de Dosimétrie Interne, Institut de Radioprotection et de Sûreté Nucléaire, 92260 Fontenay-aux-Roses (France)

    2014-05-15

    Purpose: Lipoma arborescens (LA) is a benign intra-articular lipomatous proliferation of the synovial membrane. This extremely rare condition has previously been treated by intra-articular{sup 90}Y radiosynoviorthesis but dosimetry literature on this form of radionuclide therapy is nonexistent. The authors detail methodology for successful treatment of LA and provide for the first time estimates of radiation dosimetry. The authors also analyze the biodistribution of the radiopharmaceutical over the course of the patient's treatment through sequential imaging. Methods: A patient with bilateral LA underwent intracavity injection of{sup 90}Y citrate colloid to the right and left knee joint spaces (181 and 198 MBq, respectively). SPECT/CT datasets were acquired over 9 days to quantify the biodistribution and kinetics of the radiopharmaceutical. Radiation dosimetry was performed using the MIRD schema (through OLINDA software), a custom voxel-based method, and a direct Monte Carlo calculation (OEDIPE). Results: Follow-up MRI showed marked reduction in LA size in both knees. Mean absorbed doses to the LA were 21.2 ± 0.8 and 42.9 ± 2.3 Gy using OLINDA, 8.1 ± 0.3 and 16.7 ± 0.5 Gy using voxel based methodology, and 8.2 ± 0.3 and 15.7 ± 0.5 Gy for OEDIPE in the right and left LA, respectively. Distribution of the radiopharmaceutical within the joint space alters over the imaging period, with less than 1% of the remaining activity having moved posteriorly in the knee cavity. No uptake was detected outside of the joint space after assessment with whole-body scintigraphy. Conclusions: An activity of approximately 185 MBq successfully relieved clinical symptoms of LA. There was good correlation between direct Monte Carlo and voxel based techniques, but OLINDA was shown to overestimate the absorbed dose to the tumor. Accurate dosimetry may help select an activity more tailored to the specific size and location of the LA.

  5. Radioembolisation with {sup 90}Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment

    Energy Technology Data Exchange (ETDEWEB)

    Cremonesi, Marta; Ferrari, Mahila; Pedroli, Guido [European Institute of Oncology, Unit of Medical Physics, Milan (Italy); Bartolomei, Mirco; Arico, Demetrio; De Cicco, Concetta [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Orsi, Franco; Bonomo, Guido [European Institute of Oncology, Unit of Interventistic Radiology, Milan (Italy); Mallia, Andrew [Gamma Unit, Radiology Department, St. Luke' s Hospital (Malta); Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy)

    2008-11-15

    Radioembolisation with {sup 90}Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients' dosimetric data were reviewed according to the linear-quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Twenty patients with metastatic lesions underwent radioembolisation. The {sup 90}Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting {alpha}/{beta} = 2.5 Gy (NTL), 10 Gy (tumours); T{sub 1/2,eff} = T{sub 1/2,phys} = 64.2 h; T{sub 1/2,rep} = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9-3.2) GBq, tumour dose was 130 (65-235) Gy, and tumour BED was 170 (75-360) Gy. Considering two cycles, {proportional_to}15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10-35) Gy; tumour BED increase was 10 (3-11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was {proportional_to}50 Gy (two cycles) and 65 Gy (three cycles). From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested. (orig.)

  6. {sup 90}Y microspheres prepared by sol-gel method, promising medical material for radioembolization of liver malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Łada, Wiesława, E-mail: w.lada@ichtj.waw.pl [Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Dorodna 16 (Poland); Iller, Edward [National Centre for Nuclear Research, Radioisotope Centre POLATOM, 05-400 Otwock, Andrzej Sołtan 7 (Poland); Wawszczak, Danuta [Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Dorodna 16 (Poland); Konior, Marcin, E-mail: marcin.konior@polatom.pl [National Centre for Nuclear Research, Radioisotope Centre POLATOM, 05-400 Otwock, Andrzej Sołtan 7 (Poland); Dziel, Tomasz [National Centre for Nuclear Research, Radioisotope Centre POLATOM, 05-400 Otwock, Andrzej Sołtan 7 (Poland)

    2016-10-01

    A new technology for the production of radiopharmaceutical {sup 90}Y microspheres in the form of spherical yttrium oxide grains obtained by sol-gel method has been described. The authors present and discuss the results of investigations performed in the development of new production technology of yttrium microspheres and determination of their physic-chemical properties. The final product has the structure of spherical yttrium oxide grains with a diameter 25–100 μm, is stable and free from contaminants. Irradiation of 20 mg samples of grains with diameter of 20–50 μm in the thermal neutron flux of 1.7 × 10{sup 14} cm{sup −2} s{sup −1} at the core of MARIA research nuclear reactor allowed to obtain microspheres labelled with the {sup 90}Y isotope on the way of the nuclear reaction {sup 89}Y(n, γ){sup 90}Y. Specific activity of irradiated microspheres has been determined by application of absolute triple to double coincidence ratio method (TDCR) and has been evaluated at 190 MBq/mg Y. {sup 90}Y microspheres prepared by the proposed technique can be regarded as a promising medical material for radioembolization of liver malignancies. - Highlights: • Sol-gel methods for preparation of spherical yttrium trioxide grains have been proposed. • Determination condition for irradiation {sup 89}Y{sub 2}O{sub 3} grains in nuclear reactor • Evaluation of specific activity of {sup 90}Y microspheres • Estimation of {sup 90}Y microspheres as promising medical material for radioembolization.

  7. 90Y Radioembolization Lung Shunt Fraction in Primary and Metastatic Liver Cancer as a Biomarker for Survival.

    Science.gov (United States)

    Xing, Minzhi; Lahti, Steven; Kokabi, Nima; Schuster, David M; Camacho, Juan C; Kim, Hyun S

    2016-01-01

    The aim of this study was to investigate pre-90Y lung shunt fraction (LSF) as a prognostic factor for overall survival (OS) in 90Y (resin/glass) planning 99mTc-MAA hepatopulmonary shunt studies for primary (hepatocellular carcinoma [HCC], intrahepatic cholangiocarcinoma) and metastatic liver tumors. A total of 366 consecutive patients with primary and metastatic liver tumors underwent pre-90Y shunt study and 90Y radioembolization (mean age, 59.2 years; 55% were male). MAA (mean activity, 3.65 mCi) was administered via the proper hepatic artery. Shunted lung activity was obtained by planar scintigraphy. Median LSF values for primary tumors and metastases were compared with OS from first 90Y therapy via Kaplan-Meier estimation and log-rank test. Correlations between LSF and tumor involvement on baseline cross-sectional imaging were analyzed using Pearson coefficient (r). Patients with LSF of greater than 20% were deemed unsuitable for 90Y. The study included 79 (21.5%) colorectal, 73 (20%) neuroendocrine, 70 (19.1%) HCC, 40 (10.9%) intrahepatic cholangiocarcinoma, 40 (10.9%) melanoma, 20 (5.5%) breast, and 44 (12%) other tumors including lung and pancreatic cancers. Lung shunt fractions of less than 10% and 10% to 20% were observed in 235 patients (64.2%) and 131 patients (35.8%), respectively. Median LSFs were as follows: colorectal cancer (7.60%), neuroendocrine tumor (7.01%), HCC (11.47%), cholangiocarcinoma (7.00%), melanoma (6.00%), breast cancer (7.00%), and others, including lung and pancreatic metastases to the liver (8.36%). The HCC median LSF was significantly higher than that in non-HCC tumors, 11.47% versus 7.10% (P < 0.001). High LSF (≥ 10%) in HCC correlated with poorer survival from first 90Y compared with low LSF (<10%; 4.5 vs 16.4 months, P = 0.003). Similarly, for metastatic disease, high LSF demonstrated significantly poorer survival compared with low LSF in colorectal liver metastases (13.5 vs 7.0 months, P = 0.013), neuroendocrine liver

  8. Differences in Radiation Activity Between Glass and Resin 90Y Microspheres in Treating Unresectable Hepatic Cancer.

    Science.gov (United States)

    James, Trent; Hill, Jacqueline; Fahrbach, Thomas; Collins, Zachary

    2017-03-01

    The purpose of this study was to compare the difference in prescribed radiation activity between glass and resin yttrium-90 (Y) microspheres for radioembolization of unresectable hepatocellular carcinoma (HCC) or liver metastases at a tertiary care teaching institution. The authors performed a retrospective analysis on 126 patients with primary HCC and hepatic metastatic disease from extrahepatic primary cancers who underwent radioembolization with glass or resin particles between 2008 and 2013 at their institution. Radiation activity estimates for prescribed treatments, as well as for the alternate embolization particles, were calculated using commonly employed formulae for both glass and resin particles for all treatments. A total of 217 treatments were performed on 126 patients, with 136 (62.7%) using glass particles and 81 (37.3%) using resin particles. Forty-six (36.5%) patients had metastatic colorectal cancer (CRC), 51 (40.5%) had primary HCC, while 11 (8.7%) had neuroendocrine carcinoma, and 18 (14.3%) had metastases from other primary tumors. The average prescribed activity was 2.66 GBq for glass treatments and 1.06 GBq for resin treatments across all cancer types. When the alternative treatment activity was calculated, activities were projected to decrease by an average of 1.52 GBq per treatment if resin microspheres were used instead of glass microspheres (-52.5%), while activities were projected to increase by an average of 1.57 GBq per treatment if glass microspheres were used instead of resin microspheres (148.9%; p glass microspheres.

  9. Monitoring Kidney Function in Neuroendocrine Tumor Patients Treated with 90Y-DOTATOC

    DEFF Research Database (Denmark)

    Arveschoug, Anne K; Kramer, Stine M J; Iversen, Peter;

    2015-01-01

    and during a 4-hour and a 24-hour amino acid (AA) infusion protocol. We measured the Glomerular Filtration Rate (GFR) in 28 patients before and 3, 6, 12, and 18 months after 90Y-DOTATOC therapy. We used standardized 51Cr-EDTA plasma clearance (Cr-GFR) and estimated GFR (eGFR) by the simplified 4 variable...... Modification of Diet in Renal Disease based on serum creatinine values. Further, we determined GFR in 15 patients treated with a 4-hour infusion of AA compared to 13 patients with a 24-hour infusion at 3, 6, 12 and 18 months after therapy. Pre-existing risk factors associated with kidney failure were seen...... in 82% of the patients. We observed a significant reduction in Cr-GFR up to 12 months after PRRT (mean loss 27 ml/min/1,73 m2 (32%)). The eGFR continuously overestimated the Cr-GFR with a bias of 8%. There was no significant difference between the two AA protocols, however, the 24-hour AA protocol...

  10. A complete dosimetric characterization of two {sup 90}Sr-{sup 90}Y dermatologic applicators

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, T.S. [Instituto de Pesquisas Energeticas e Nucleares, IPEN/CNEN, Sao Paulo (Brazil); Fernandes, M.A.R. [Faculdade de Medicina de Botucatu, UNESP, Departamento de Dermatologia e Radioterapia, Sao Paulo (Brazil); Yoriyaz, H., E-mail: hyoriyaz@ipen.b [Instituto de Pesquisas Energeticas e Nucleares, IPEN/CNEN, Sao Paulo (Brazil); Antonio, P.L. [Instituto de Pesquisas Energeticas e Nucleares, IPEN/CNEN, Sao Paulo (Brazil)

    2011-03-11

    A complete dosimetric characterization of two Amershan {sup 90}Sr-{sup 90}Y dermatologic applicators is described in this present work. The dosimetric parameters analyzed are: percentage depth dose curve, radial dose distribution, non-uniformity and asymmetry. Both applicators are planar-circular having 22.57 and 9.0 mm diameters. In the range where the percentage depth dose goes from 100% down to 20%, the measured percentage depth dose and that obtained by the Monte Carlo simulation have shown maximum discrepancy of 5.3% for both applicators. The radial dose distribution has been measured at several depths using a GafChromic EBT QD+ films and it was also calculated by simulation. The discrepancies found did not exceed 5.9% up to the depth of 1.8 mm, where the percentage depth dose drops to 40% of the maximum. The maximum non-uniformity and asymmetry are 1.7% and 5.3% for the first applicator and 22.7% and 25.9% for the second applicator, respectively. Both applicators meet the specification for the maximum non-uniformity established by the adopted protocol, whose limit is 30%. As for the asymmetry the limit is 20% and the second applicator exceeded it in about 5.9%.

  11. A complete dosimetric characterization of two 90Sr- 90Y dermatologic applicators

    Science.gov (United States)

    Coelho, T. S.; Fernandes, M. A. R.; Yoriyaz, H.; Antonio, P. L.

    2011-03-01

    A complete dosimetric characterization of two Amershan 90Sr- 90Y dermatologic applicators is described in this present work. The dosimetric parameters analyzed are: percentage depth dose curve, radial dose distribution, non-uniformity and asymmetry. Both applicators are planar-circular having 22.57 and 9.0 mm diameters. In the range where the percentage depth dose goes from 100% down to 20%, the measured percentage depth dose and that obtained by the Monte Carlo simulation have shown maximum discrepancy of 5.3% for both applicators. The radial dose distribution has been measured at several depths using a GafChromic® EBT QD+ films and it was also calculated by simulation. The discrepancies found did not exceed 5.9% up to the depth of 1.8 mm, where the percentage depth dose drops to 40% of the maximum. The maximum non-uniformity and asymmetry are 1.7% and 5.3% for the first applicator and 22.7% and 25.9% for the second applicator, respectively. Both applicators meet the specification for the maximum non-uniformity established by the adopted protocol, whose limit is 30%. As for the asymmetry the limit is 20% and the second applicator exceeded it in about 5.9%.

  12. Dosimetry characterization of the commercial CaF{sub 2} for beta radiation of {sup 90}Sr + {sup 90}Y; Caracterizacao dosimetrica de CaF{sub 2} comercial para radiacao beta de {sup 90}Sr + {sup 90}Y

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Mercia L.; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: mlolivei@ipen.br, e-mail: lcaldas@ipen.br

    2003-07-01

    This work studies the dosimetric characteristics of the CaF{sub 2} commercial dosimetry for detection of {sup 90}Sr + {sup 90}Y beta radiation for using in the calibration of flat and concave appliers. Were determined the repetitiousness and linearity of answers of the samples, and their calibration curves.

  13. 瘤内注射90Y-SAg治疗小鼠肝癌移植瘤的实验研究%Experimental study of intratumor injection of 90Y-SAg for the treatment of liver cancer in mice

    Institute of Scientific and Technical Information of China (English)

    牟培源; 陈靖; 王建晨; 何千舸; 蒋小良; 金美娟; 李芳

    2006-01-01

    目的:探讨瘤内注射放射性核素钇-90(90Y)与超抗原(SAg)混悬液90Y-SAg治疗小鼠肝癌移植瘤的效果.方法:30只荷瘤小鼠随机分为三组,每组10只,分别瘤内注射0.1 ml SAg和0.1 ml (100 μci)90Y(A组)、0.1 ml (100 μci)90Y(B组)、0.1 ml SAg(C组). 结果:注射后2周:B组、C组肿瘤生长率分别为0.18±0.12和0.21±0.17,两组差异不显著(P>0.05);A组呈负生长,生长率为-0.28±0.23,与B组和C组比较均有显著性差异(P<0.01);A、B、C三组肿瘤坏死率分别为0.36±0.18、0.11±0.09、0.10±0.06, B组和C组均为轻度坏死,两组间差异不显著(P>0.05),A组为中度坏死,与B组和C组比较有显著性差异(P<0.01). 结论:瘤内注射90Y-SAg疗效优于单一的 90Y或SAg注射,是一种有效的治疗小鼠肝癌移植瘤方法.

  14. (90)Y microspheres prepared by sol-gel method, promising medical material for radioembolization of liver malignancies.

    Science.gov (United States)

    Łada, Wiesława; Iller, Edward; Wawszczak, Danuta; Konior, Marcin; Dziel, Tomasz

    2016-10-01

    A new technology for the production of radiopharmaceutical (90)Y microspheres in the form of spherical yttrium oxide grains obtained by sol-gel method has been described. The authors present and discuss the results of investigations performed in the development of new production technology of yttrium microspheres and determination of their physic-chemical properties. The final product has the structure of spherical yttrium oxide grains with a diameter 25-100μm, is stable and free from contaminants. Irradiation of 20mg samples of grains with diameter of 20-50μm in the thermal neutron flux of 1.7×10(14)cm(-2)s(-1) at the core of MARIA research nuclear reactor allowed to obtain microspheres labelled with the (90)Y isotope on the way of the nuclear reaction (89)Y(n, ɤ)(90)Y. Specific activity of irradiated microspheres has been determined by application of absolute triple to double coincidence ratio method (TDCR) and has been evaluated at 190MBq/mg Y. (90)Y microspheres prepared by the proposed technique can be regarded as a promising medical material for radioembolization of liver malignancies.

  15. A systematic comparative evaluation of 90Y-labeled bifunctional chelators for their use in targeted therapy.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2014-02-01

    This paper describes a systematic comparative evaluation of five commonly used bifunctional chelators, namely,p-isothiocyanato benzyl derivatives of diethylenetriaminepentacetic acid (DTPA-NCS), trans-cyclohexyl diethylenetriaminepentaceticacid (CHX-A″-DTPA-NCS), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NCS), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS), and 3,6,9,15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA-NCS), on the basis of their ability to complex 90Y at room temperature, in vitro and in vivo stability and clearance pattern in biological system. The results of the experiments carried out revealed that CHX-A″-DTPA-NCS was the most promising option as it could be radiolabeled with 90Y at room temperature with highest specific activity and demonstrated high in vitro stability in human serum and in presence of challenging metal ions commonly present inhuman plasma. The clearance pattern in Swiss mice revealed that 90Y-CHX- A″-DTPA-NCS cleared through the kidneys with minimum retention in any other major organ. Thus, the use of cyclohexyl-DTPA based bifunctional chelators would increase the scope of making 90Y-labeled agents suitable for targeted therapy.

  16. Feasibility of bremsstrahlung dosimetry for direct dose estimation in patients undergoing treatment with {sup 90}Y-ibritumomab tiuxetan

    Energy Technology Data Exchange (ETDEWEB)

    Arrichiello, C.; Aloj, L.; Mormile, M.; D' Ambrosio, L.; Caraco, C.; De Martinis, F. [Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ' ' G. Pascale' ' , Nuclear Medicine Department, Napoli (Italy); Frigeri, F.; Arcamone, M.; Pinto, A. [Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ' ' G. Pascale' ' , Hematology-Oncology, Napoli (Italy); Stem Cells Transplantation Unit, Department of Hematology, Napoli (Italy); Lastoria, S. [Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ' ' G. Pascale' ' , Nuclear Medicine Department, Napoli (Italy); Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ' ' G. Pascale' ' , IRCCS, Napoli (Italy)

    2012-06-15

    Radioimmunotherapy with {sup 90}Y-ibritumomab tiuxetan has been used successfully used in the treatment of CD20-positive non-Hodgkin's lymphoma (NHL). Pretherapy imaging with {sup 111}In-ibritumomab tiuxetan has been used in provisional dosimetry studies. Posttherapy imaging of {sup 90}Y-ibritumomab tiuxetan for clinical use is appealing as it would simplify the data acquisition process and allow measurements of actual doses absorbed during treatment. The study included 29 patients with non-Hodgkin's lymphoma, of whom 16 (group I) received a pretherapy {sup 111}In-ibritumomab tiuxetan diagnostic study and {sup 90}Y-ibritumomab tiuxetan treatment 1 week later, and 13 (group II) received only {sup 90}Y-ibritumomab tiuxetan treatment. Planar imaging and blood sampling were performed in all patients. The doses absorbed by organs at risk were calculated using a whole-body average attenuation correction factor (relative dosimetry approach) and, in the case of the {sup 111}In-ibritumomab tiuxetan image sets, also using organ-specific attenuation correction factors (absolute dosimetry method). Red marrow absorbed doses were based on gamma counting of blood samples. The estimated red marrow absorbed doses from {sup 111}In and {sup 90}Y data were equivalent. In all cases, the doses absorbed by organs at risk were found to be within prescribed limits. The relative dosimetry approach applied to both the {sup 90}Y and {sup 111}In data significantly underestimated the doses relative to those obtained with the {sup 111}In absolute dosimetry method which is generally accepted as the reference method (MIRD 16). In the case of {sup 111}In, the relative dosimetry approach values were highly correlated (R {sup 2} = 0.61) with the reference method values. Relative dosimetry estimates may be adjusted multiplying by a correction factor of 2.8. The {sup 90}Y-ibritumomab tiuxetan relative dosimetry data correlated poorly with the reference method values (R {sup 2} = 0.02). Based

  17. Gastric injury from {sup 90}Y to left hepatic lobe tumors adjacent to the stomach: fact or fiction?

    Energy Technology Data Exchange (ETDEWEB)

    Gates, Vanessa L.; Hickey, Ryan; Marshall, Karen; Williams, Melissa; Salzig, Krystina; Lewandowski, Robert J. [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Salem, Riad [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States)

    2015-12-15

    Radioembolization with {sup 90}Y microspheres is a locoregional radiation therapy for unresectable hepatic neoplasm. Non-target delivery of {sup 90}Y microspheres resulting in gastrointestinal (GI) symptoms is a recognized complication; there is minimal knowledge regarding the radiation effect to the gastric wall from left hepatic lobe {sup 90}Y treatments. Our aim was to study the incidence of GI complications when the target tissue (hepatic parenchyma ± tumor) is in close proximity to the gastric wall. We hypothesized that liver (tumor) to stomach proximity does not correlate with increased toxicity. Between November 2011 and September 2013, we studied all patients who underwent left lobe radioembolization with {sup 90}Y glass microspheres. With Institutional Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these patients, identifying a subset of patients with the left hepatic lobe <1 cm from the gastric wall. Patients were seen in clinic 1 month posttreatment and subsequently at 3-month intervals. Short- and long-term gastric adverse events were tabulated. Ninety-seven patients successfully underwent left hepatic lobe {sup 90}Y microsphere radioembolization in which the average distance from the liver to the stomach wall was 1.0 ± 2.8 mm. The average dose for patients who received radioembolization to the left hepatic lobe was 109 ± 57 Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose for patients who received radioembolization to the left hepatic lobe with tumor within 1 cm of the gastric wall was 121 ± 41 Gy. There were no reportable or recordable medical events. Of the patients, 34 % reported abdominal pain that was grade 1-2; 65 % of the patients reported no abdominal pain. None of the 97 patients developed a clinically evident GI ulcer. Patients with left lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic radiation effects following radioembolization with glass

  18. Intra-arterial treatment with {sup 90}Y microspheres for hepatocellular carcinoma: 4 years experience at the Ghent University Hospital

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, Bieke; Mertens, Jeroen; Oltenfreiter, Ruth [Ghent University Hospital, Department of Nuclear Medicine, Ghent (Belgium); Sturm, Emiel; Defreyne, Luc [Ghent University Hospital, Department of Vascular and Interventional Radiology, Ghent (Belgium); Smeets, Peter [Ghent University Hospital, Department of Radiology, Ghent (Belgium); Troisi, Roberto [Ghent University Hospital, Department of Hepatobiliary Surgery and Liver Transplantation, Ghent (Belgium); Vlierberghe, Hans van [Ghent University Hospital, Department of Gastroenterology and Hepatology, Ghent (Belgium)

    2011-12-15

    We report on our experience in terms of eligibility, safety, response and survival for treatment of hepatocellular carcinoma (HCC) with {sup 90}Y microspheres. Secondly, we investigated the urinary excretion of {sup 90}Y following treatment. We retrospectively reviewed all HCC patients referred to our department for {sup 90}Y microsphere treatment. We recorded reasons for not proceeding to actual treatment. In case treatment was performed, we assessed the tolerance (Common Terminology Criteria for Adverse Events v3.0, CTCAE v3.0), the response [modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria] and long-term survival (Kaplan-Meier). The urinary excretion was estimated by 12-h urine collections post-injection for analysis in a gamma counter. Forty-three HCC patients were referred for radioembolization. Fourteen patients were excluded, mainly due to unfavourable {sup 99m}Tc-macroaggregated albumin (MAA) distribution. Twenty-nine patients were treated with {sup 90}Y microspheres (TheraSphere, mean activity 2.17 GBq). In four patients severe clinical adverse events were encountered, however only in one case clearly related to the therapy. Twenty patients were assessable by mRECIST: complete response in 15%, partial response in 35%, stable disease in 30% and progression in 20% were observed. A median survival of 12.3 months (95% confidence interval 9.4-15.2) was estimated. Concerning the substudy on urinary excretion, only 0.0025% of the administered activity was excreted in the urine within the first 12 h following TheraSphere. Following a strict workup before admitting patients to radioembolization with TheraSphere, we found good clinical tolerance in the vast majority of patients. Radiological response assessment yielded an overall response rate of 50%, when evaluated early following treatment. Urine analysis showed consistently only low activities of {sup 90}Y excreted in the urine. (orig.)

  19. Determining the effects of microsphere and surrounding material composition on {sup 90}Y dose kernels using egsnrc and mcnp5

    Energy Technology Data Exchange (ETDEWEB)

    Paxton, Adam B.; Davis, Stephen D.; DeWerd, Larry A. [Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705 (United States); Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705 and McGill University Health Centre, Department of Medical Physics, Montreal, Quebec H3G 1A4 (Canada); Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705 (United States)

    2012-03-15

    Purpose: Recent advances in the imaging of {sup 90}Y using positron emission tomography (PET) and improved uncertainty in the branching ratio for the internal pair production component of {sup 90}Y decay allow for a more accurate determination of the activity distribution of {sup 90}Y microspheres within a patient. This improved activity distribution can be convolved with the dose kernel of {sup 90}Y to calculate the dose distribution within a patient. This work investigates the effects of microsphere and surrounding material composition on {sup 90}Y dose kernels using egsnrc and mcnp5 and compares the results of these two transport codes. Methods: Monte Carlo simulations were performed with egsnrc and mcnp5 to calculate the dose rate at multiple radial distances around various {sup 90}Y sources. Point source simulations were completed with mcnp5 to determine the optimal electron transport settings for this work. After determining the optimal settings, point source simulations were completed using egsnrc (user code edknrc) and mcnp5 in water and liver [as defined by the International Commission on Radiation Units and Measurements (ICRU) Report 44]. The results were compared to ICRU Report 72 reference data. Point source simulations were also completed in water with a density of 1.06 g{center_dot}cm{sup -3} to evaluate the effect of the density of the surrounding material. Glass and resin microsphere simulations were performed with average and maximum diameter and density values (based on values given in the literature) in water and in liver. The results were compared to point source simulation results using the same transport code and in the same surrounding material. All simulations had statistical uncertainties less than 1%. Results: The optimal transport settings in mcnp5 for this work included using the energy-and step-specific algorithm (DBCN 17J 2) and ESTEP set to 10. These settings were used for all subsequent simulations with mcnp5. The point source

  20. Role of neutron and proton system in spin cut off parameter and entropy of 89,90Y

    Science.gov (United States)

    Rahmatinejad, A.; Razavi, R.; Kakavand, T.

    2015-09-01

    The nuclear level densities, entropies and spin cut off parameters have been determined in 89,90Y nuclei using the BCS model with inclusion of pairing interaction. The results have a good agreement with the recent experimental data on the level densities measured by the Oslo group. In addition, the entropy excess of 90Y compared to 89Y as a function of temperature has been extracted. Also, the role of neutron and proton systems in the entropy excess as well as the spin cut off excess have been investigated using the entropy excess ratio and spin cut off excess ratio introduced in our previous publication. The role of the neutron system at low temperatures, the temperatures below critical temperature, in the semi-magic nucleus 89Y is similar compared to the closed shell proton system in the tin isotopes.

  1. Role of neutron and proton system in spin cut off parameter and entropy of {sup 89,90}Y

    Energy Technology Data Exchange (ETDEWEB)

    Rahmatinejad, A. [Department of Physics, Faculty of Science, University of Zanjan, Zanjan (Iran, Islamic Republic of); Razavi, R., E-mail: rrazavin@ihu.ac.ir [Physics Department, Faculty of Science, Imam Hossein Comprehensive University, Tehran (Iran, Islamic Republic of); Kakavand, T. [Department of Physics, Faculty of Science, Imam Khomeini International University, Qazvin (Iran, Islamic Republic of)

    2015-09-15

    The nuclear level densities, entropies and spin cut off parameters have been determined in {sup 89,90}Y nuclei using the BCS model with inclusion of pairing interaction. The results have a good agreement with the recent experimental data on the level densities measured by the Oslo group. In addition, the entropy excess of {sup 90}Y compared to {sup 89}Y as a function of temperature has been extracted. Also, the role of neutron and proton systems in the entropy excess as well as the spin cut off excess have been investigated using the entropy excess ratio and spin cut off excess ratio introduced in our previous publication. The role of the neutron system at low temperatures, the temperatures below critical temperature, in the semi-magic nucleus {sup 89}Y is similar compared to the closed shell proton system in the tin isotopes.

  2. Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post Radioembolization 90Y PET

    Directory of Open Access Journals (Sweden)

    Shyam Mohan Srinivas

    2014-10-01

    Full Text Available Background: Radioembolization with Yttrium-90 (90Y microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC. Using post-treatment 90Y PET/CT scans,the distribution of microspheres within the liver can be determined and quantitatively assessesed . We studied the radiation dose of 90Y delivered to liver and treated tumors.Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres® to the frequency of complications with mRECIST. 90Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL to an absorbed dose (Gy.Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90-120 Gy;range 0-570 Gy. Tumor response by mRECIST criteria was performed for 48 tumors that had follow up scans. There were 21 responders (mean dose 215 Gy and 27 nonresponders (mean dose 167 Gy. The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p=0.099. Normal liver tissue received a mean dose of 67 Gy (mode 60-70 Gy; range 10-120 Gy. There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p=0.036.Conclusion: Our cohort of patients showed a possible dose response trend for the tumors. Collateral dose to normal liver is nontrivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose which the tumor or normal liver received.

  3. Development of anthropomorphic hand phantoms for personal dosimetry in 90Y-Zevalin preparation and patient delivering.

    Science.gov (United States)

    Ciolini, R; d'Errico, F; Traino, A C; Paternostro, E; Laganà, A; Romei, C; Pazzagli, F; Del Gratta, A

    2014-01-01

    Anthropomorphic tissue-equivalent hand phantoms were achieved to measure the extremity dose involved in Zevalin (90)Y-labelling and patient delivering procedure for radioimmunotherapy treatment of non-Hodgkin lymphoma. The extremity doses to hands and wrists of operators were measured by using thermoluminescent detectors mounted on the developed phantoms. Measurements of chest- and lens-equivalent doses performed on a Rando phantom are also reported.

  4. Dosimetric comparison of electron beam and 9{sup 0}Sr+{sup 90}Y applicator for keloids treatment

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, Talita S.; Tada, Ariane; Antonio, Patricia L.; Yoriyaz, Helio, E-mail: tasallesc@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Fernandes, Marco A.R., E-mail: marco@cetea.com.b [UNESP, Botucatu, SP (Brazil). Faculdade de Medicina. Dept. de Dermatologia e Radioterapia Rubiao Junior

    2009-07-01

    Studies have been shown that among several methods that have been used for the treatment of keloids the surgical excision followed by the adjuvant radiotherapy presents the lowest relapsed rate of the injury. In this work a comparative dosimetric study has been performed using a 4 MeV electron beam from a Varian Clinac 2100C linear accelerator at the radiotherapy service of the Hospital das Clinicas of UNESP-HC, Botucatu-SP and an Amershan {sup 90}Sr+{sup 90}Y brachytherapy applicator with 1491 MBq of activity. Percentage depth dose curves from ionization chamber measurements and through Monte Carlo simulation have been obtained and compared. Dose measurements have been obtained using parallel plates ionization chamber (Esradin A12) and extrapolation mini-chamber developed at IPEN. The dose calculations have been obtained using the well-known Monte Carlo radiation transport code MCNP-4C. Maximum dose differences obtained between measured/calculated values for {sup 90}Sr+{sup 90}Y applicator and for the electron beam were, respectively: 7.8 % and 8.0%. The profiles of the depth and superficial tissue dose distribution produced by the electron beam revealed themselves flatter and more homogeneous than those produced by the {sup 90}Sr+{sup 90}Y applicator, especially to wider fields, which cannot be obtained with beta therapy applicators because of their geometric limitations. In conclusion this present work has shown that {sup 90}Sr+{sup 90}Y applicators could be efficient for small and very superficial lesions but in most cases electron beam sources are more adequate especially for large and deeper lesions. (author)

  5. Update on the rational use of (90Y-ibritumomab tiuxetan in the treatment of follicular lymphoma

    Directory of Open Access Journals (Sweden)

    Martina Lehnert

    2009-07-01

    Full Text Available Martina Lehnert, Heinz Ludwig, Niklas Zojer 1st Department of Medicine, Center for Oncology and Hematology, Wilhelminenspital, Vienna, AustriaAbstract: The development of radiolabeled antibodies against CD20 has facilitated targeted treatment of follicular lymphoma (FL. By using 90Y-ibritumomab tiuxetan (Zevalin®, a radionuclide (yttrium-90, linked by the chelator tiuxetan to the antibody ibritumomab is brought into the vicinity of lymphoma cells. By the so-called cross-fire effect, this beta emitter has the capacity to destroy not only the lymphoma cells having bound the antibody, but also neighboring lymphoma cells. Currently this antibody is licensed in the European Union for use in relapsed or refractory FL. It is anticipated that this drug will also be approved for use as consolidation therapy after successful first-line treatment. Here we first will review the published literature supporting the use of 90Y-ibritumomab tiuxetan in the aforementioned indications and emerging data showing applicability of ibritumomab tiuxetan as sole first-line therapy for FL, as well as in the transplant setting. Possible strategies of incorporating ibritumomab tiuxetan into the treatment algorithm of FL are discussed.Keywords: follicular lymphoma, 90Y-ibritumomab tiuxetan

  6. Development and biological evaluation of {sup 90}Y-BPAMD as a novel bone seeking therapeutic agent

    Energy Technology Data Exchange (ETDEWEB)

    Rabiei, Ali; Shamsaei, Mojtaba [Amir Kabir University of Technology, Tehran (Iran, Islamic Republic of). Energy Engineering and Physics Dept.; Yousefnia, Hassan; Zolghadri, Samaneh; Jalilian, Amir Reza [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Enayati, Razieh [Islamic Azad Univ. (IAU), Tehran (Iran, Islamic Republic of). Faculty of Engineering

    2016-07-01

    Nowadays, the bone-seeking radiopharmaceuticals play an important role in the treatment of the bone-related pathologies. Whereas various phosphonate ligands have already been identified, a DOTA-based bisphosphonate, 4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) -1,4,7,10-tetraazacyclododec-1-yl (BPAMD) with better characteristics has recently been synthesized. In this study, {sup 90}Y-BPAMD was developed with radiochemical purity >98% and the specific activity of 3.52 TBq/mmol in the optimized conditions as a new bone-seeking therapeutic agent. The complex demonstrated significant stability at room temperature and in human serum even after 48 h. At even low amount of hydroxyapatite (5 mg), more than 90% binding to hydroxyapatite was observed. Biodistribution studies after injection of the complex into the Syrian rats showed major accumulation of the labelled compound in the bone tissue and an insignificant uptake in the other organs all the times after injection. Generally, {sup 90}Y-BPAMD demonstrated interesting characteristics compared to the other {sup 90}Y bone-seeking agents and even {sup 166}Ho-BPAMD, and can be considered as a new bone-seeking candidate for therapeutic applications.

  7. Hepatic Toxicity After Radioembolization of the Liver Using {sup 90}Y-Microspheres: Sequential Lobar Versus Whole Liver Approach

    Energy Technology Data Exchange (ETDEWEB)

    Seidensticker, Ricarda; Seidensticker, Max; Damm, Robert; Mohnike, Konrad [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany); Schuette, Kerstin; Malfertheiner, Peter [Universitaetsklinikum Magdeburg, Klinik fuer Gastroenterologie, Hepatologie und Infektiologie (Germany); Buskirk, Mark Van [Data Reduction (United States); Pech, Maciej; Amthauer, Holger; Ricke, Jens, E-mail: jens.ricke@med.ovgu.de [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany)

    2012-10-15

    Purpose: {sup 90}Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus 'whole liver' {sup 90}Y-radioembolization. Methods: Thirty-four patients with liver malignancy in noncirrhotic livers were included; {sup 90}Y-radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12 weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed. Results: Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P < 0.05). Three patients treated with whole liver RE suffered from radioembolization-induced liver disease (REILD). Pathological increases in bilirubin at 3 months were observed for the whole liver group only (52.3 vs. 18.7 {mu}mol/l, P = 0.012). Total liver volume did not change significantly in either group, but shrinkage of the initially treated hepatic lobe with compensatory hypertrophy of the subsequently treated lobe was observed in the sequential lobar group (P < 0.05). Portal vein diameter increased significantly in whole liver-treated patients only (+17% vs. +6.6%, P = 0.043). Conclusions: Noncirrhotic patients undergoing sequential lobar radioembolization had less hepatic toxicity compared to whole liver embolization. The sequential approach should be the preferred strategy.

  8. 188Re标记叶酸偶联白蛋白纳米微球对SKOV3人卵巢癌生长抑制作用研究*%The Inhibitory Effects of 188Re-Labeled Folate Coupling with Magnetic Albumin Nanoparticles on SKOV3 Ovarian Cancer in Vivo

    Institute of Scientific and Technical Information of China (English)

    唐秋莎; 陈道桢; 臧嘉; 郭彩琴

    2013-01-01

    Objective To investigate the effects of isotope labeled folate targeting albumin nanoparticles (188Re-fo-late-CDDP/HAS MNP) on human SKOV3 ovarian cancer cells in vivo. Methods The human SKOV3 ovarian cancer model was established in mice. Sixty-four tumor-bearing mice were randomly divided into eight groups:(A) negative control group, (B) chemotherapy group, (C) radiotherapy alone group, (D) hyperthermia alone group, (E) chemotherapy combined with radio-therapy group, (F) chemotherapy combined with hyperthermia therapy group, (G) radiotherapy combined with hyperthermia therapy group and (H) hyperthermia, chemotherapy and radiotherapy combined treatment group. After treatment, the cell pro-liferation and tumor growth were observed. The inhibitory rate of tumor mass was measured. The histopathological changes of tumor were observed in all groups. Results The quality of tumor was significantly lower in treatment groups than that of control group (P<0.05). There was the lowest quality of tumor in hyperthermia, chemotherapy and radiotherapy combined treatment group than that of other treatment groups (P<0.05). Conclusion The combination of magnetic induction hyper-thermia, chemotherapy, targeted radionuclide of radiation exposure can effectively inhibit the growth of ovarian cancer, which has the potential application for ovarian cancer treatment.%目的观察核素标记叶酸靶向白蛋白纳米微球(188Re-folate-CDDP/HAS MNP)对SKOV3人卵巢癌细胞生长作用的影响。方法建立人卵巢癌细胞SKOV3裸鼠模型,并将64只荷瘤鼠随机分成8组,每组8只,分别为(A)阴性对照组;(B)采用CDDP方案化疗的单纯化疗组;(C)核素靶向内照射的单纯放疗组;(D)磁感应热疗的单纯热疗组;(E)化疗联合放疗组;(F)化疗联合热疗治疗组;(G)放疗联合热疗治疗组;(H)热疗、化疗、放疗联合治疗组。各组经治疗后,观察肿瘤生长增殖情况,计算肿瘤质量抑

  9. Clinical and laboratory toxicity after intra-arterial radioembolization with (90y-microspheres for unresectable liver metastases.

    Directory of Open Access Journals (Sweden)

    Maarten L J Smits

    Full Text Available OBJECTIVE: To investigate clinical and laboratory toxicity in patients with unresectable liver metastases, treated with yttrium-90 radioembolization ((90Y-RE. METHODS: Patients with liver metastases treated with (90Y-RE, between February 1(st 2009 and March 31(st 2012, were included in this study. Clinical toxicity assessment was based on the reporting in patient's charts. Laboratory investigations at baseline and during a four-month follow-up were used to assess laboratory toxicity according to the Common Terminology Criteria for Adverse Events version 4.02. The occurrence of grade 3-4 laboratory toxicity was stratified according to treatment strategy (whole liver treatment in one session versus sequential sessions. Response assessment was performed at the level of target lesions, whole liver and overall response in accordance with RECIST 1.1 at 3- and 6 months post-treatment. Median time to progression (TTP and overall survival were calculated by Kaplan-Meier analysis. RESULTS: A total of 59 patients, with liver metastases from colorectal cancer (n = 30, neuroendocrine tumors (NET (n = 6 and other primary tumors (n = 23 were included. Clinical toxicity after (90Y-RE treatment was confined to grade 1-2 events, predominantly post-embolization symptoms. No grade 3-4 clinical toxicity was observed, whereas laboratory toxicity grade 3-4 was observed in 38% of patients. Whole liver treatment in one session was not associated with increased laboratory toxicity. Three-months disease control rates for target lesions, whole liver and overall response were 35%, 21% and 19% respectively. Median TTP was 6.2 months for target lesions, 3.3 months for the whole liver and 3.0 months for overall response. Median overall survival was 8.9 months. CONCLUSION: The risk of severe complications or grade 3-4 clinical toxicity in patients with liver metastases of various primary tumors undergoing (90Y-RE is low. In contrast, laboratory toxicity grade 3

  10. Thermoluminescent dosimetry of beta radiations of {sup 90} Sr/ {sup 90} Y using amorphous ZrO{sub 2}; Dosimetria termoluminiscente de radiaciones beta de {sup 90} Sr/ {sup 90} Y usando ZrO{sub 2} amorfo

    Energy Technology Data Exchange (ETDEWEB)

    Rivera M, T. [CICATA-Legaria, IPN, Legaria Num. 694, 11500 Mexico D.F. (Mexico); Olvera T, L.; Azorin N, J.; Barrera R, M.; Soto E, A.M. [UAM-I, 09340 Mexico D.F. (Mexico)

    2005-07-01

    In this work the results of studying the thermoluminescent properties (Tl) of the zirconium oxide in its amorphous state (ZrO{sub 2}-a) before beta radiations of {sup 90} Sr/ {sup 90} Y are presented. The amorphous powders of the zirconium oxide were synthesized by means of the sol-gel technique. The sol-gel process using alkoxides like precursors, is an efficient method to prepare a matrix of zirconium oxide by hydrolysis - condensation of the precursor to form chains of Zr-H{sub 3} and Zr-O{sub 2}. One of the advantages of this technique is the obtention of gels at low temperatures with very high purity and homogeneity. The powders were characterized by means of thermal analysis and by X-ray diffraction. The powders of ZrO{sub 2}-a, previously irradiated with beta particles of {sup 90} Sr/{sup 90} Y, presented a thermoluminescent curve with two peaks at 150 and 257 C. The dissipation of the information of the one ZrO{sub 2}-a was of 40% the first 2 hours remaining constant the information for the following 30 days. The reproducibility of the information was of {+-} 2.5% in standard deviation. The studied characteristics allow to propose to the amorphous zirconium oxide as thermoluminescent dosemeter for the detection of beta radiation. (Author)

  11. Thermoluminescent dosimetry of beta radiations of {sup 90} Sr/ {sup 90} Y using ZrO{sub 2}: Eu; Dosimetria termoluminiscente de radiaciones beta de {sup 90} Sr/ {sup 90} Y usando ZrO{sub 2}: Eu

    Energy Technology Data Exchange (ETDEWEB)

    Olvera T, L.; Azorin N, J.; Barrera S, M.; Soto E, A.M. [UAM-I, 09340 Mexico D.F. (Mexico); Rivera M, T. [CICATA-IPN, Legaria 694, 11500 Mexico D.F. (Mexico)

    2005-07-01

    In this work the results of studying the thermoluminescent properties (TL) of the doped zirconium oxide with europium (ZrO{sub 2}: Eu{sup 3+}) before beta radiations of {sup 90}Sr/ {sup 90}Y are presented. The powders of ZrO{sub 2}: Eu{sup 3+} were obtained by means of the sol-gel technique and they were characterized by means of thermal analysis and by X-ray diffraction. The powders of ZrO{sub 2}: Eu{sup 3+}, previously irradiated with beta particles of {sup 90}Sr/ {sup 90}Y, presented a thermoluminescent curve with two peaks at 204 and 292 C respectively. The TL response of the ZrO{sub 2}: Eu{sup 3+} as function of the absorbed dose was lineal from 2 Gy up to 90 Gy. The fading of the information of the ZrO{sub 2}: Eu{sup 3+} was of 10% the first 2 hours remaining almost constant the information by the following 30 days. The ZrO{sub 2} doped with the (Eu{sup 3+}) ion it was found more sensitive to the beta radiation that the one of zirconium oxide without doping (ZrO{sub 2}) obtained by the same method. Those studied characteristics allow to propose to the doped zirconium oxide with europium like thermoluminescent dosemeter for the detection of the beta radiation. (Author)

  12. Development of a dosimetric system for {sup 90}Sr + {sup 90}Y betatherapy applicators; Desenvolvimento de um sistema de dosimetria para aplicadores de betaterapia de {sup 90}Sr + {sup 90}Y

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, Talita Salles

    2010-07-01

    The {sup 90}Sr+{sup 90}Y applicators, used in betatherapy for prevention of keloids and pterigium, are imported and many times their dosimetric features are shown only in an illustrated form by the manufacturers. The exhaustive routine of the medical physicists in the clinic do not make possible the accomplishment of procedures for the confirmation of these parameters. This work presents the development of a methodology for the dosimetry of {sup 90}Sr+{sup 90}Y betatherapy applicators. The Monte Carlo code MCNP5 was used for the simulation of the percentage depth dose curves and dose distribution profiles produced by these applicators. The experimental measurements of the radial and axial radiation attenuation, have been done with a mini-extrapolation chamber, thermoluminescent dosimeters and radiographic films. The experimental results have been compared with the simulated values. Both percentage depth dose curves and the radial dose profiles, the theoretical and the experimental ones, have presented good agreement, which may validate the use of the MCNP5 for these simulations, confirming the viability of the usage of this method in procedures of beta emitter sources dosimetry. (author)

  13. Studies on production of high specific activity {sup 99}Mo and {sup 90}Y by Szilard Chalmers reaction

    Energy Technology Data Exchange (ETDEWEB)

    Tomar, B.S.; Steinebach, O.M.; Terpstra, B.E.; Bode, P.; Wolterbeek, H.T. [TU Delft (Netherlands). Section for Radiation and Isotopes for Health

    2010-07-01

    Attempts have been made to use Szilard Chalmers reaction to prepare {sup 99}Mo and {sup 90}Y in high specific activity. Experiments were carried out using irradiation of freshly prepared oxinate complexes of molybdenum and yttrium in the HOR reactor of Reactor Institute at TU Delft. The irradiated target was dissolved in dichloromethane and the radionuclides were separated by solvent extraction into aqueous phase. Detailed investigations on the effect of pH of aqueous solution, irradiation time and target amount was also carried out to optimize the enrichment factor and yield. The highest enrichment factor for {sup 99}Mo was found to be around 200 with a yield close to 30%. In the case of {sup 90}Y, solvent extraction method did not yield high enrichment factors. Slightly higher enrichment factors were achieved with ion exchange method. Studies were also carried out with yttrium oxide nano-powder. Speciation study of {sup 99}Mo in the separated aqueous fraction showed it to be present as {sup 99}MoO{sub 4}{sup 2-} ion. The results appear to be quite promising for large scale production of {sup 99}Mo for medical applications. (orig.)

  14. {sup 18}F-FDG PET/CT predicts survival after {sup 90}Y transarterial radioembolization in unresectable hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jreige, Mario; Mitsakis, Periklis; Gucht, Axel van der; Pomoni, Anastasia; Silva-Monteiro, Marina; Boubaker, Ariane; Nicod-Lalonde, Marie; Prior, John O.; Schaefer, Niklaus [Lausanne University Hospital, Department of Nuclear Medicine and Molecular Imaging, Lausanne (Switzerland); Gnesin, Silvano [Lausanne University Hospital, Institute of Radiation Physics, Lausanne (Switzerland); Duran, Rafael; Denys, Alban [Lausanne University Hospital, Department of Radiodiagnostic and Interventional Radiology, Lausanne (Switzerland)

    2017-07-15

    To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 ({sup 90}Y-TARE) for unresectable hepatocellular carcinoma (uHCC). We analysed data from 48 patients in our prospective database undergoing {sup 90}Y-TARE treatment for uHCC (31 resin, 17 glass). All patients underwent {sup 18}F-FDG PET/CT and morphological imaging (CT and MRI scans) as part of a pretherapeutic work-up. Patients did not receive any treatment between these imaging procedures and {sup 90}Y-TARE. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were used to assess the prognostic value of {sup 18}F-FDG PET/CT metabolic parameters, including SUV{sub max}, tumour-to-liver (T/L) uptake ratio and SUV{sub mean} of healthy liver, and morphological data, including number and size of lesions, portal-venous infiltration (PVI). Relevant prognostic factors for HCC including Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumour size, PVI and serum AFP level were compared with metabolic parameters in univariate and multivariate analyses. The median follow-up in living patients was 16.2 months (range 11.4-50.1 months). Relapse occurred in 34 patients (70.8%) at a median of 7.4 months (range 1.4-27.9 months) after {sup 90}Y-TARE, and relapse occurred in 24 of 34 patients (70.8%) who died from their disease at a median of 8.1 months (range 2.2-35.2 months). Significant prognostic markers for PFS were the mean and median lesion SUV{sub max} (both P = 0.01; median PFS 10.2 vs. 7.4 months), and significant prognostic markers for OS were the first quarter (Q1) cut-off values for lesion SUV{sub max} and T/L uptake ratio (both P = 0.02; median OS 30.9 vs. 9 months). The multivariate analysis confirmed that lesion SUV{sub max} and T/L uptake ratio were independent negative predictors of PFS (hazard ratio, HR, 2.7, 95% CI 1.2-6.1, P = 0.02, for mean

  15. Production of large quantities of {sup 90}Y by ion-exchange chromatography using an organic resin and a chelating agent

    Energy Technology Data Exchange (ETDEWEB)

    Xiques Castillo, Abmel, E-mail: axcastillo@yahoo.co [Centro de Isotopos (CENTIS), Ave. Monumental y Carretera La Rada Km 3 1/2, Guanabacoa, Havana (Cuba); Perez-Malo, Marylaine; Isaac-Olive, Keila [Centro de Isotopos (CENTIS), Ave. Monumental y Carretera La Rada Km 3 1/2, Guanabacoa, Havana (Cuba); Mukhallalati, Heyam [Division of Radiopharmaceuticals, Atomic Energy Commission of Syria, Damascus (Syrian Arab Republic); Casanova Gonzalez, Edgar; Torres Berdeguez, Mirta [Centro de Isotopos (CENTIS), Ave. Monumental y Carretera La Rada Km 3 1/2, Guanabacoa, Havana (Cuba); Cornejo Diaz, Nestor [Centro de Proteccion e Higiene de las Radiaciones, AP: 6195 Habana 6, CP 10600, Havana (Cuba)

    2010-11-15

    The performance of a system composed of an organic cation exchanger (Dowex 50Wx8) and a chelating agent (EDTA) previously described for the successful production of {sup 90}Y via a {sup 90}Sr/{sup 90}Y generator is assessed under dynamic conditions. In an attempt to overcome the established limitation of ion-exchange resins for the separation of subcurie quantities of activity, {sup 90}Y is repeatedly isolated from an 11.8-GBq (320 mCi) {sup 90}Sr cow using a three-column tandem arrangement. The high recovery and radionuclidic purity obtained for {sup 90}Y and the parameters of the separation (time, eluant concentration, pH and flow rate range) strongly suggest that Ci quantities of {sup 90}Y can be handled satisfactorily by the ion-exchange method. No replacement or treatment of the cow, low waste generation and {sup 90}Sr losses less than 0.1% after each run were observed during the present study which, in combination with the low cost of this resin, may result in an attractive alternate method for the production of large quantities of {sup 90}Y.

  16. {sup 99m}Tc-MAA/{sup 90}Y-Bremsstrahlung SPECT/CT after simultaneous Tc-MAA/{sup 90}Y-microsphere injection for immediate treatment monitoring and further therapy planning for radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadzadehfar, Hojjat; Sabet, Amir; Muckle, Marianne; Reichmann, Karl; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Wilhelm, Kai [University Hospital Bonn, Department of Radiology, Bonn (Germany)

    2011-07-15

    An angiographic evaluation combined with {sup 99m}Tc-macroaggregated albumin (Tc-MAA) scanning should precede the treatment of any selected candidates for radioembolization (RE) of the liver. If the tumours in one liver lobe have not been targeted in the test angiogram, it should be repeated. However, in a few cases treatment of one liver lobe or at least some segments is safe and feasible and performing a repeated test angiogram with Tc-MAA (Re-MAA) in a separate session leads to more radiation exposure and could be time consuming. Our aim was to evaluate the feasibility of concurrent RE of a part of the liver and therapy planning for another region by simultaneous injection of the Tc-MAA and {sup 90}Y-microspheres in two different locations in the therapy session. Tc-MAA and bremsstrahlung (BS) single photon emission computed tomography (SPECT)/CT were performed separately in an effort to distinguish between the distributions of these two different radiopharmaceuticals. RE was combined with a simultaneous second test angiogram of another lobe or segments in the same session in six patients [44-70 years; five women (83%)]. Five patients suffered from colorectal carcinoma (CRC) and one from ovarian cancer. Tc-MAA and BS SPECT/CT were performed for all cases. Post-therapeutic Tc-MAA SPECT/CT showed in all patients only the distribution of Tc-MAA without any detectable BS. Evaluation of {sup 90}Y-microsphere distribution was not always possible in the post-therapeutic BS scan performed 24 h later due to remaining Tc-MAA radiation. However, scans performed at 48 h post-intervention no longer showed any Tc-MAA ''contamination''. Combining RE and Re-MAA is feasible in appropriately selected patients. (orig.)

  17. Positron-emitting resin microspheres as surrogates of {sup 90}Y SIR-Spheres: a radiolabeling and stability study

    Energy Technology Data Exchange (ETDEWEB)

    Avila-Rodriguez, Miguel A. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States)]. E-mail: maavilarodri@wisc.edu; Selwyn, Reed G. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); Hampel, Joseph A. [Waisman Center, University of Wisconsin, Madison, WI 53706 (United States); Thomadsen, Bruce R. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); DeJesus, Onofre T. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); Converse, Alexander K. [Waisman Center, University of Wisconsin, Madison, WI 53706 (United States); Nickles, Robert J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States)

    2007-07-15

    Commercially available resin microspheres and SIR-Spheres were labeled with metallic positron emitters and evaluated as positron emission tomography (PET) imaging surrogates of {sup 90}Y SIR-Spheres. Radiolabeling was performed using a batch method, and in vitro stability over 24 h was evaluated in saline at physiological pH at 37{sup o}C. The activity per microsphere distribution, as evaluated by autoradiography, showed the activity per microsphere to be proportional to the square radius of the spheres, suggesting surface binding. The in vivo stability of radiolabeling was evaluated in rats by micro-PET imaging after the intravenous injection of labeled microspheres. The different resin microspheres and radionuclides evaluated in this study all showed good radiolabeling efficiency and in vitro stability. However, only resins labeled with {sup 86}Y and {sup 89}Zr proved to have the in vivo stability required for clinical applications.

  18. Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus {sup 90}Y-radioembolization for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Johannes M.; Xing, Minzhi [Yale School of Medicine, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Zhang, Di [University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (United States); Kim, Hyun S. [Yale School of Medicine, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Yale School of Medicine, Yale Cancer Center, New Haven, CT (United States)

    2017-05-15

    To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 ({sup 90}Y)-radioembolization for hepatocellular carcinoma (HCC). Studies comparing conventional (c)TACE versus {sup 90}Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus {sup 90}Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger's and Begg's tests. Fourteen studies comparing DEB-TACE or {sup 90}Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over {sup 90}Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. DEB-TACE and {sup 90}Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to {sup 90}Y-radioembolization but direct comparison is warranted for further evaluation. (orig.)

  19. Preparation and 177Lu Labeling of p-SCN-Bn-DOTA-h-R3

    Institute of Scientific and Technical Information of China (English)

    DENG; Xin-rong; FAN; Cai-yun; LUO; Zhi-fu

    2013-01-01

    The humanized monoclonal antibodies(mAbs)h-R3 has been used as a targeting biomolecule better than other anti-EGFR(epidermal growth factor receptor)for the delivery of radionuclide onto tumor cells in radio immunotherapy(RIT).Several bifunctional chelating agents(BCAs)could be used as a bridge coupling h-R3 and radiometals.In this study,h-R3 was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,

  20. Preparation, Radiolabelling and Biodistribution Study of ~(177)Lu-DTPA-G3

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Polyamidoamine (PAMAM) dendrimers are new artificial macromolecules with tree-like structure and have characteristics of greater water-solubility, bioavailability and compatibility. It can be carried by the drug molecules. PAMAM have been

  1. Production of {sup 177}Lu, a potential radionuclide for diagnostic and therapeutic applications

    Energy Technology Data Exchange (ETDEWEB)

    Khandaker, Mayeen Uddin; Kassim, Hasan Abu [Department of Physics, University of Malaya, 50603 Kuala Lumpur (Malaysia); Haba, Hiromitsu [Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan)

    2015-04-24

    {sup 177g}Lu (T{sub 1/2}=6.647d; E{sub β{sup −max}}=498.3KeV, I{sub β{sup −total}}=100%; E{sub γ} = 112.9498 keV, I{sub γ} = 6.17%; E{sub γ} = 208.3662 keV, I {sub γ} = 10.36%) is widely used in many clinical procedures due to its excellent decay characteristics. Production cross-sections of the {sup nat}Yb(d,x){sup 177g}Lu reactions have been measured from a 24-MeV deuteron energy down to the threshold by using a stacked-foil activation technique combined with high resolution γ-ray spectrometry. An overall good agreement is found with some of the earlier measurements, whereas a partial agreement is obtained with the theoretical data extracted from the TENDL-2013 library. Physical thick target yield for the {sup 177g}Lu radionuclide was deduced using the measured cross-sections. The deduced yield curves indicate that a low energy (<11 MeV) cyclotron and a highly enriched {sup 176}Yb target could be used to obtain {sup 177g}Lu with negligible impurity from {sup 177m}Lu.

  2. Molecular response assessed by {sup 68}Ga-DOTANOC and survival after {sup 90}Y microsphere therapy in patients with liver metastases from neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Luca; Salvatori, Rita; Bagni, Oreste [Santa Maria Goretti Hospital, Department of Nuclear Medicine, Latina (Italy); Scopinaro, Francesco [Sant' Andrea Hospital, Department of Nuclear Medicine, Rome (Italy); Pelle, Giuseppe; Cianni, Roberto [Santa Maria Goretti Hospital, Department of Interventional Radiology, Latina (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy)

    2016-03-15

    We investigated the prognostic role of {sup 68}Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing {sup 90}Y radioembolization ({sup 90}Y-RE). A group of 15 consecutive patients with unresectable NET liver metastases underwent {sup 68}Ga-DOTANOC PET at baseline and 6 weeks after {sup 90}Y-RE. Molecular response was defined as a reduction of >50 % in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50 % and nonresponders with ΔT/S <50 %) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following {sup 90}Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). A decrease in T/S ratio was seen in all patients on {sup 68}Ga-DOTANOC PET scans performed after {sup 90}Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. Molecular response assessed with {sup 68}Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with {sup 90}Y-RE. (orig.)

  3. Rapid determination of {sup 90}Sr impurities in freshly 'generator eluted'{sup 90}Y for radiopharmaceutical preparation

    Energy Technology Data Exchange (ETDEWEB)

    Bonardi, Mauro L. [LASA, Universita degli Studi di Milano and INFN-Milano, via F.lli Cervi 201, I-20090 Segrate, Milano (Italy); Martano, Luigi [Division of Nuclear Medicine, European Institute of Oncology, via G. Ripamonti 435, I-20141 Milano (Italy); Groppi, Flavia [LASA, Universita degli Studi di Milano and INFN-Milano, via F.lli Cervi 201, I-20090 Segrate, Milano (Italy); Chinol, Marco [Division of Nuclear Medicine, European Institute of Oncology, via G. Ripamonti 435, I-20141 Milano (Italy)], E-mail: marco.chinol@ieo.it

    2009-10-15

    {sup 90}Y is one of the most useful radionuclides for radioimmunotherapeutic applications and has a half-life (t{sub 1/2}=64.14 h) suitable for most therapeutic applications, beta particles of high energy and decays to a stable daughter. It is significant that {sup 90}Y is available conveniently and inexpensively from a radionuclide 'generator' by decay of its parent, {sup 90}Sr. Nevertheless, current and planned clinical applications with [{sup 90}Y] labelled compounds employ activity levels that cannot be readily obtained from an in-house generator, but from commercial sources. We have evaluated Eichrom's Sr-resin, either as an 'in-house' generator or as a fast QC method for analysis of {sup 90}Y solutions. In particular, for the development as a generator, we investigated the percentage of the radio-Sr in the first 8 M HNO{sub 3} eluate: in this fraction the concentration of {sup 90}Sr must be smaller than 10{sup -5}% (recommendations of the International Commission on Radiological Protection). For evaluation as a rapid QC method, we analyzed the concentration of {sup 90}Y in all the fractions containing 'only' radio-Sr: {sup 90}Y should not be present in these eluates. After the collection of {beta}{sup -} and {gamma} spectra and analysis of them, we concluded that commercial Sr-resin minicolumn cannot give us the results expected; we developed an in-house system loaded with 4 mL of Sr-resin which gave better results as a generator and a rapid QC method.

  4. Thin CaSO{sub 4}:Dy thermoluminescent dosimeters for calibration of {sup 90}Sr+{sup 90}Y applicators

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, Patricia L. [Instituto de Pesquisas Energeticas e Nucleares, Comissao Nacional de Energia Nuclear, Av. Prof. Lineu Prestes, 2242, 05508-000, Sao Paulo, SP (Brazil); Oliveira, Mercia L. [Centro Regional de Ciencias Nucleares, Comissao Nacional de Energia Nuclear, Av. Prof. Luis Freire, 200, 50740-540, Recife, PE (Brazil); Caldas, Linda V.E., E-mail: lcaldas@ipen.br [Instituto de Pesquisas Energeticas e Nucleares, Comissao Nacional de Energia Nuclear, Av. Prof. Lineu Prestes, 2242, 05508-000, Sao Paulo, SP (Brazil)

    2012-04-15

    Clinical applicators are used in brachytherapy to treat superficial lesions of skin and eye. They should be periodically calibrated according to quality control programs and international recommendations. Thin CaSO{sub 4}:Dy thermoluminescent dosimeters were used to calibrate various applicators with a dermatological applicator as a reference. The obtained absorbed dose rates were compared with those quoted in their calibration certificates. Depth-dose curves were constructed for all the applicators. A mail dosimetry system was developed for calibration of clinical applicators. - Highlights: Black-Right-Pointing-Pointer Absorbed dose rates were obtained for {sup 90}Sr+{sup 90}Y applicators using CaSO{sub 4}:Dy pellets. Black-Right-Pointing-Pointer Depth-dose curves were obtained for all studied applicators. Black-Right-Pointing-Pointer CaSO{sub 4}:Dy dosimeters presented satisfactory results in all realized tests. Black-Right-Pointing-Pointer A mail dosimetry system was developed with CaSO{sub 4}:Dy pellets.

  5. Electrochemical separation of 90-yttrium in the electrochemical 90Sr/90Y generator and its use for radiolabelling of DOTA-conjugated somatostatin analog [DOTA0, Tyr3] octreotate

    Directory of Open Access Journals (Sweden)

    Petrović Đorđe Ž.

    2012-01-01

    Full Text Available Radiopharmaceuticals based on 90Y are widely used in the treatment of malignant deseases. In order to meet the requirements for their future application, a 90Sr/90Y generator was developed and 90Y eluted from this locally produced generator was used for the radiolabelling of the DOTA-conjugated somatostatin analog [DOTA0,Tyr3] octreotate and the preparation of [90Y-DOTA0,Tyr3] octreotate (90Y-DOTATATE for peptide receptore radionuclide therapy. 90Sr/90Y generator was based on the electrochemical separation of 90Y from 90Sr in a two-cycle electrolysis procedure. Three electrode cells were used to perform both electrolyses. In both cycles, working electrodes were kept on constant potential. The pH of the solution was adjusted to 2.7 of the value before the electrolyses. The radionuclidic purity of the 90Y solution was analysed by ITLC and extraction paper chromatography. The labelling of peptide (100 mg DOTATATE with 90YCl3 was performed at 95°C for 30 minutes. Radiochemical purity was determined by HPLC and chromatographic separation, using a solid SepPak C-18 column. Results obtained confirmed the efficiency of our electrochemical separation technique and quality control methods for 90Y. The achieved efficiency of the 90Sr/90Y generator above 96% of the theoretical value represents a good basis for the further development of this generator. The labelling of the DOTATATE with 90Y exhibited a high efficiency, too: there was less than 1% of 90Y3+in the 90Y-DOTATATE.

  6. Calculation of electron and isotopes dose point kernels with FLUKA Monte Carlo code for dosimetry in nuclear medicine therapy

    CERN Document Server

    Mairani, A; Valente, M; Battistoni, G; Botta, F; Pedroli, G; Ferrari, A; Cremonesi, M; Di Dia, A; Ferrari, M; Fasso, A

    2011-01-01

    Purpose: The calculation of patient-specific dose distribution can be achieved by Monte Carlo simulations or by analytical methods. In this study, FLUKA Monte Carlo code has been considered for use in nuclear medicine dosimetry. Up to now, FLUKA has mainly been dedicated to other fields, namely high energy physics, radiation protection, and hadrontherapy. When first employing a Monte Carlo code for nuclear medicine dosimetry, its results concerning electron transport at energies typical of nuclear medicine applications need to be verified. This is commonly achieved by means of calculation of a representative parameter and comparison with reference data. Dose point kernel (DPK), quantifying the energy deposition all around a point isotropic source, is often the one. Methods: FLUKA DPKS have been calculated in both water and compact bone for monoenergetic electrons (10-3 MeV) and for beta emitting isotopes commonly used for therapy ((89)Sr, (90)Y, (131)I, (153)Sm, (177)Lu, (186)Re, and (188)Re). Point isotropic...

  7. Human anti-mouse IgM and IgG responses in ovarian cancer patients after radioimmunotherapy with 90Y-muHMFG1.

    NARCIS (Netherlands)

    Oei, A.L.M.; Sweep, F.C.; Geurts-Moespot, A.; Tienoven, D. van; Mensdorff-Pouilly, S von; Thomas, C.M.G.; Massuger, L.F.A.G.

    2008-01-01

    BACKGROUND: Human anti-mouse antibody (HAMA)-IgM and IgG in ovarian cancer patients treated with intraperitoneal (i.p.) 90Y-muHMFG1 as consolidating therapy were analyzed for a relationship with outcome of disease. PATIENTS AND METHODS: Serial serum samples from 208 ovarian cancer patients

  8. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    Directory of Open Access Journals (Sweden)

    Marincek Nicolas

    2013-01-01

    Full Text Available Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle, 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158 months, 34 (range: 1–118 months and 29 (range: 1–113 months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59 vs. intermediate dose, p = 0.03 and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79 vs. low dose, p = 0.03. Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211.

  9. Comparison of yttrium and indium complexes of DOTA-BA and DOTA-MBA: models for (90)Y- and (111)In-labeled DOTA-biomolecule conjugates.

    Science.gov (United States)

    Liu, Shuang; Pietryka, John; Ellars, Charles E; Edwards, D Scott

    2002-01-01

    Yttrium and indium complexes of 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetylbenzylamine (DOTA-BA) and 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetyl-R-(+)-alpha-methylbenzylamine (DOTA-MBA) were prepared in order to study solution structures of (90)Y- and (111)In-labeled DOTA-biomolecule conjugates. (90)Y and (111)In complexes M(L) (M = (90)Y and (111)In; L = DOTA-BA and DOTA-MBA) were prepared from the reaction of MCl(3) with DOTA-BA and DOTA-MBA, respectively, in ammonium acetate buffer. A reverse phase HPLC method revealed that both (90)Y and (111)In complexes show only one radiometric peak in their radio-HPLC chromatograms. It was also found that (111)In(DOTA-BA) and (111)In(DOTA-MBA) are more hydrophilic than their corresponding (90)Y analogues, suggesting different coordination spheres in (111)In and (90)Y complexes of the same DOTA conjugate. Complexes M(L) (M = Y and In; L = DOTA-BA and DOTA-MBA) were prepared and characterized by HPLC, LC-MS, and NMR ((1)H and (13)C) methods. The HPLC concordance experiments for (90)Y(DOTA-MBA)/Y(DOTA-MBA) and (111)In(DOTA-MBA)/In(DOTA-MBA) show that the same complex is prepared at both tracer and macroscopic levels. The NMR data ((1)H and (13)C) clearly demonstrates that Y(DOTA-BA) and Y(DOTA-MBA) exist in solution as one predominant isomer. VT NMR data ((1)H and (13)C) show that In(DOTA-BA) and In(DOTA-MBA) are fluxional at room temperature while Y(DOTA-BA) and Y(DOTA-MBA) become fluxional only at elevated temperatures. The fluxionality of these complexes is due to rapid rotation of acetate/acetamide chelating arms and inversion of ethylenic groups of the macrocyclic ring.

  10. {sup 99m}Tc-labelled macroaggregated albumin (MAA) scintigraphy for planning treatment with {sup 90}Y microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, Bieke; Mertens, Jeroen; Stienaers, Steven; D' Asseler, Yves [Ghent University Hospital, Department of Nuclear Medicine, Ghent (Belgium); Sturm, Emiel J.; Defreyne, Luc [Ghent University Hospital, Department of Interventional Radiology, Ghent (Belgium)

    2010-12-15

    {sup 90}Y microspheres are used for intra-arterial treatment of liver tumours. In the patient preparation, a hepatic angiogram is performed and all arteries that could transport microspheres from the targeted liver vasculature to extrahepatic organs are blocked. {sup 99m}Tc-labelled macroaggregated albumin (MAA) is injected intra-arterially to simulate the treatment and whole-body scintigraphy and single photon emission computed tomography (SPECT) of the abdomen are performed. Various aspects of lung shunt fraction (LSF) estimation were studied: interobserver and intrapatient variability, influence of scan quality and underlying disease. Secondly, the interobserver variability in reading the MAA SPECT of the abdomen was investigated. We reviewed 90 whole-body scans and 20 SPECT scans performed at our institution. Readers were blinded to each other's findings. Scoring the scan quality was based on the visualization of tracer degradation. The mean difference in LSF between the readers was 1%. In 1 of 23 patients who underwent repeated MAA injections a marked change in LSF was observed. No significant differences in LSF were recorded for primary versus secondary liver tumours. There was a correlation between scan quality and LSF, suggesting that low scan quality leads to overestimation of the LSF. Concordant results in ruling out the presence of extrahepatic tracer deposition were reached in 17 of 20 scans (85%). Interobserver and intrapatient variability in LSF calculation was limited. LSF was clearly dependent on scan quality. The underlying disease had no significant impact on the LSF. Interobserver variability for reading the MAA SPECT scans was acceptable. (orig.)

  11. Selective intraarterial radionuclide therapy with yttrium-90 (Y-90 microspheres for hepatic neuroendocrine metastases: Initial experience at a single center

    Directory of Open Access Journals (Sweden)

    Arslan Nuri

    2011-01-01

    Full Text Available Background/Aim. Selective intraarterial radionuclide therapy (SIRT with Yttrium-90 (Y-90 microspheres is also known as radioembolization and delivers high doses of radiation to hepatic tumors with minimum healthy liver exposure. The aim of this study was to present our preliminary experience in the role of liver directed radiotherapy with Y-90 microspheres for the treatment of unresectable hepatic metastases from neuroendocrine tumors (NET. Methods. The results of SIRT in 10 patients (5 males, 5 females; mean age 48.7 years; age range 24-73 years with metastatic liver disease from NETs during the period from April 2008 through August 2010 were reviewed. All patients had meticulous pre- and post-imaging studies as a part of their work-up procedure, as well as serologic tests of liver function to determine the extent of liver function damage. The patients who were eligible for SIRT had pretreatment visceral angiography to define and occlude non-target arteries. Results. The mean ± SD administered SIR-Spheres® activity was 1.49 ± 0.42 GBq (range 0.72-2.21 GBq in all the patients. These treatments delivered a dose of 99.73 ± 66.36 Gy (range 49- 420.8 Gy to the target tumors. The estimated dose to the lungs and normal liver was 4.45 ± 1.95 Gy (range 2.4-8.5 Gy and 26.73 ± 14.19 Gy (range 5-58.9 Gy, respectively. Overall response rate of 90% and patient tolerance was satisfactory for most patients. Conclusion. From our limited experience, we can conclude that SIRT with Y-90 microspheres is a safe and efficacious treatment option for patients with liver metastasis of NET without any serious side effects.

  12. Evaluation of EGS4/PRESTA multiple-scattering algorithms for 90Sr/90Y intravascular brachytherapy dosimetry.

    Science.gov (United States)

    Wang, R; Li, X A; Yu, C X

    2000-08-01

    The purpose of this work is to evaluate the EGS4/PRESTA electron multiple-scattering (MS) algorithms for dose calculation in intravascular brachytherapy (IVBT) using a 90Sr/90Y source. The small source size and the small volume of interest in IVBT require very fine spatial resolution, which may break down the constraints of Molière's MS theory as implemented in EGS4. The theory is accurate only when the electron step sizes are large enough to allow the number of collisions omega0 to be much greater than e = 2.7183. When step sizes are too small to allow at least 2.7183 collisions, as may be necessitated by the fine geometry, the algorithm may switch off MS, producing dosimetric artefacts. This study showed that switching off MS could produce a dose deviation of up to 6% when the half-thickness (d/2) of the dose scoring region is comparable with the Moliere minimum step size (t(min) = 2.7183). The effect of switching off MS is negligible if d/2 > t(min) For the case of omega0 > e, if the electron step sizes are chosen to allow five to 40 collisions, with increasing step size, the doses surrounding the source increase and the error decreases. On the other hand, when larger step sizes are chosen, the dose calculation voxel size must also be increased in order for the calculations to converge. A good compromise between accuracy and applicability for IVBT simulation can be made, if the thickness of the scoring region is 0.1 mm and the electron step sizes are in the range allowing 10 to 30 collisions.

  13. Development of Reactor RIs and Radiation Sources

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ul Jae; Han, H. S.; Lee, J. S. [KAERI, Daejeon (Korea, Republic of); and others

    2010-04-15

    This project aimed to develop radioisotopes and radiation sources, which are employed radiotherapy in medical fields and process diagnoses and measurements in industry. Major accomplishments are as followed. {center_dot} Development of Non-Carrier-Added Therapeutic RI's - Developed the core separation processes by using novel adsorbents - Succeeded commercial scale production of non-carrier-added {sup 177}Lu and developed production processes for {sup 147}Pm and {sup 47}Sc {center_dot} Demonstration of {sup 188}W/{sup 188}Re generator technology and prototype product - Demonstrated 1 Ci generator (30 times better performance than commercial products) - Developed pilot-scale production system, and supplied generators for the development of radiopharmaceuticals {center_dot} Development of {sup 90}Sr/{sup 90}Y Generator System - Developed core adsorbents for the RI separation - Constructed Proto type generator and demonstrated for 500mCi production - Demonstrated the production of radiopharmaceutical grade {sup 90}Y : 100 {approx} 10,000 purer than commercially available products - Constructed pilot scale generator system for regular production of {sup 90}Y {center_dot}Development of {beta}-ray sources for thickness measurements and brachytherapy - Developed {sup 90}Sr thickness gauge source and received KOLAS certification - Developed and tested for the possibility of the application of a {beta}-ray source to brachytherapy of eye diseases. - Completed safety accessment of the P-32brachytherapy source {center_dot}Development of Small Focal {gamma}-ray Source for Radiography - Developed the source and tested in real conditions: 28.5% improvement in radiography quality compared to a regular source - Technology-transferred for earlier commercialization {center_dot}Extraction of RI Mixture from Irradiated Natural Uranium without Dissolution - Multi-step separation of fission products for useful RI's - Developed six adsorbents and tested for the separation of

  14. {sup 18}F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with {sup 90}Y microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Haug, Alexander R. [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany); Klinikum Grosshadern, Department of Nuclear Medicine, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University, Department of Internal Medicine III, Munich (Germany); Bruns, Christiane J. [Ludwig-Maximilians-University, Department of Surgery, Munich (Germany); Hoffmann, Ralf; Jakobs, Tobias [Ludwig-Maximilians-University, Institute of Clinical Radiology, Munich (Germany); Bartenstein, Peter; Hacker, Marcus [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany)

    2011-06-15

    {sup 90}Y radioembolization has emerged as a valuable therapy for intrahepatic cholangiocellular carcinomas (ICC). We aimed to evaluate the prognostic power of FDG PET/CT and that of pretherapeutic scintigraphy with {sup 99m}Tc-labelled macroagglutinated albumin (MAA), an index of tumour vascularization. The study group comprised 26 consecutive patients suffering from nonresectable ICC. Before treatment with radioembolization, all patients underwent MRI of the liver, as well as MAA scintigraphy, which was followed immediately by SPECT(/CT) to quantify the liver-lung shunt fraction. Using image fusion, regions of interest were drawn around the tumours and the entire liver, and the tumour-to-liver quotient was calculated. In addition, FDG PET/CT was performed at baseline and 3 months after radioembolization, and the percentage changes in peak ({delta}SUV{sub max}) and mean ({delta}SUV{sub mean}) FDG uptake and in metabolic tumour volume ({delta}Vol{sub 2SD}) relative to baseline were calculated. Treatment response at 3 months was also assessed using contrast-enhanced MRI and CT on the basis of standard criteria. Of 23 patients in whom follow-up MRI was available, 5 (22%) showed a partial response, 15 (65%) stable disease and 3 (13%) progressive disease. The change in all FDG values significantly predicted survival by Kaplan-Meier analysis after radioembolization; {delta}Vol{sub 2SD} responders had a median survival of 97 weeks versus 30 weeks in nonresponders (P = 0.02), whereas {delta}SUV{sub max} and {delta}SUV{sub mean} responders had a median survival of 114 weeks (responder) versus 19 weeks (nonresponder) and 69 weeks in patients with stable disease (P < 0.05). Pretherapeutic MAA scintigraphy or MRI did not predict survival, nor did the presence of extrahepatic metastases, or prior therapies. Only {delta}Vol{sub 2SD} was significantly associated with survival by univariate analysis (hazard ratio 0.25; P = 0.04) and multivariate analysis (hazard ratio 0.20, P = 0

  15. Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90 microspheres for unresectable primary and metastatic liver tumors

    Directory of Open Access Journals (Sweden)

    Ozkan Elgin

    2011-08-01

    Full Text Available Abstract Background The aim of this study was to evaluate the success of selective intraarterial radionuclide therapy (SIRT with Yttrium-90 (Y-90 microspheres in liver metastases of different tumors. We also interpreted the contribution of SIRT to survival times according to responder- non responder and hepatic- extra hepatic disease. Methods The clinical and follow-up data of 124 patients who were referred to our department for SIRT between June 2006 and October 2010 were evaluated retrospectively. SIRT has been applied to 78 patients who were suitable for treatment. All the patients had primary liver tumor or unresectable liver metastasis of different malignancies. The treatment was repeated at least one more time in 5 patients to the same or other lobes. Metabolic treatment response evaluated by fluorine-18 fluorodeoxyglucose (F18-FDG positron emission tomography/computed tomography (PET/CT in the 6th week after treatment. F18-FDG PET/CT was repeated in per six weeks periods. The response criterion had been described as at least 20% decrease of SUV value. Also in patients with neuroendocrine tumor serial Gallium-68 (Ga-68 PET/CT was used for evaluation of response. Patients were divided into 2 groups according to their treatment response. Results 68 patients received treatment for the right lobe, seven patients received treatment for the left lobe and 3 patients for both lobes. The mean treatment dose was estimated at 1.62 GBq. In the evaluation of treatment response; 43(55% patients were responder (R and 35 (45% patients were non-responder (NR in the sixth week F18-FDG PET/CT. Mean pretreatment SUVmax value of R group was 11.6 and NR group was 10.7. While only 11 (31% out of 35 NR patients had H disease, 30 (69% out of 43 R patients had H disease (p Conclusions SIRT is a useful treatment method which can contribute to the lengthening of survival times in patients with primary or metastatic unresectable liver malignancies. Also F18-FDG PET

  16. Optimization of energy window for {sup 90}Y bremsstrahlung SPECT imaging for detection tasks using the ideal observer with model-mismatch

    Energy Technology Data Exchange (ETDEWEB)

    Rong Xing; Ghaly, Michael; Frey, Eric C. [Department of Radiology, Johns Hopkins University, Baltimore, Maryland 21287-0859 (United States)

    2013-06-15

    Purpose: In yttrium-90 ({sup 90}Y) microsphere brachytherapy (radioembolization) of unresectable liver cancer, posttherapy {sup 90}Y bremsstrahlung single photon emission computed tomography (SPECT) has been used to document the distribution of microspheres in the patient and to help predict potential side effects. The energy window used during projection acquisition can have a significant effect on image quality. Thus, using an optimal energy window is desirable. However, there has been great variability in the choice of energy window due to the continuous and broad energy distribution of {sup 90}Y bremsstrahlung photons. The area under the receiver operating characteristic curve (AUC) for the ideal observer (IO) is a widely used figure of merit (FOM) for optimizing the imaging system for detection tasks. The IO implicitly assumes a perfect model of the image formation process. However, for {sup 90}Y bremsstrahlung SPECT there can be substantial model-mismatch (i.e., difference between the actual image formation process and the model of it assumed in reconstruction), and the amount of the model-mismatch depends on the energy window. It is thus important to account for the degradation of the observer performance due to model-mismatch in the optimization of the energy window. The purpose of this paper is to optimize the energy window for {sup 90}Y bremsstrahlung SPECT for a detection task while taking into account the effects of the model-mismatch. Methods: An observer, termed the ideal observer with model-mismatch (IO-MM), has been proposed previously to account for the effects of the model-mismatch on IO performance. In this work, the AUC for the IO-MM was used as the FOM for the optimization. To provide a clinically realistic object model and imaging simulation, the authors used a background-known-statistically and signal-known-statistically task. The background was modeled as multiple compartments in the liver with activity parameters independently following a

  17. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma.

    Science.gov (United States)

    Janik, John E; Morris, John C; O'Mahony, Deirdre; Pittaluga, Stefania; Jaffe, Elaine S; Redon, Christophe E; Bonner, William M; Brechbiel, Martin W; Paik, Chang H; Whatley, Millie; Chen, Clara; Lee, Jae-Ho; Fleisher, Thomas A; Brown, Maggie; White, Jeffrey D; Stewart, Donn M; Fioravanti, Suzanne; Lee, Cathryn C; Goldman, Carolyn K; Bryant, Bonita R; Junghans, Richard P; Carrasquillo, Jorge A; Worthy, Tat'Yana; Corcoran, Erin; Conlon, Kevin C; Waldmann, Thomas A

    2015-10-20

    Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody (90)Y-daclizumab. (90)Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with (90)Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25(-) provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated (90)Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients.

  18. Sustained safety and efficacy of extended-shelf-life {sup 90}Y glass microspheres: long-term follow-up in a 134-patient cohort

    Energy Technology Data Exchange (ETDEWEB)

    Lewandowski, Robert J.; Minocha, Jeet; Memon, Khairuddin; Riaz, Ahsun; Gates, Vanessa L.; Ryu, Robert K.; Sato, Kent T.; Omary, Reed; Salem, Riad [Northwestern University, Department of Radiology, Chicago, IL (United States)

    2014-03-15

    To validate our initial pilot study and confirm sustained safety and tumor response of extended-shelf-life {sup 90}Y glass microspheres. We hypothesized that for the same planned tissue dose, the increase in number of glass microspheres (decayed to the second week of their allowable shelf-life) administered for the same absorbed dose would result in better tumor distribution of the microspheres without causing additional adverse events. Between June 2007 and January 2010, 134 patients underwent radioembolization with extended-shelf-life {sup 90}Y glass microspheres; data from 84 new patients were combined with data from our 50-patient pilot study cohort. Baseline and follow-up imaging and laboratory data were obtained 1 and 3 months after therapy and every 3 months thereafter. Clinical and biochemical toxicities were prospectively captured and categorized according to the Common Terminology Criteria. Response in the index lesion was assessed using WHO and EASL guidelines. The mean delivered radiation dose was 123 Gy to the target liver tissue. The mean increase in number of microspheres with this approach compared to standard {sup 90}Y glass microsphere dosimetry was 103 %, corresponding to an increase from 3.84 to 7.78 million microspheres. Clinical toxicities included fatigue (89 patients, 66 %), abdominal pain (49 patients, 36.6 %), and nausea/vomiting (25 patients, 18.7 %). Grade 3/4 bilirubin toxicity was seen in three patients (2 %). Two (1 %) of the initial 50-patient cohort showed gastroduodenal ulcers; gastroduodenal ulcers were not seen in any of the subsequent 84 patients. According to WHO and EASL guidelines, response rates were 48 % and 57 %, respectively, and 21 % demonstrated a complete EASL response. This study showed sustained safety and efficacy of extended-shelf-life {sup 90}Y glass microspheres in a larger, 134-patient cohort. The increase in number of microspheres administered theoretically resulted in better tumor distribution of the

  19. Influence of time delay on the estimated lung shunt fraction on 99mTc-labeled MAA scintigraphy for 90Y microsphere treatment planning.

    Science.gov (United States)

    De Gersem, Ruth; Maleux, Geert; Vanbilloen, Hubert; Baete, Kristof; Verslype, Chris; Haustermans, Karin; Verbruggen, Alfons; Van Cutsem, Eric; Deroose, Christophe Michel

    2013-12-01

    90Y-microspheres therapy is used to treat selected patients with primary or metastatic liver tumors in a safe and effective way. As a preparation for 90Y-microspheres treatment, a 99mTc-macroaggregated albumin (99mTc-MAA) simulation procedure is essential to evaluate particle shunting to the lung or gastrointestinal tract. We investigated the effect of interval between injection of 99mTc-MAA and time of scanning on the lung shunt fraction (LSF). In 4 patients with secondary hepatic malignancies who underwent repeated whole-body scintigraphy up to 5 hours after injection of 99mTc-MAA, a marked change in LSF was observed. It appears that tracer degradation leads to an important overestimation of LSF at later time points. An overestimation of LSF can lead to dose reduction or canceling of the planned 90Y-microspheres treatment. It is concluded that the interval between injection and scanning should be kept as short as possible.

  20. Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models.

    Directory of Open Access Journals (Sweden)

    Aya Sugyo

    Full Text Available Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that 89Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR, is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT with 90Y-TSP-A01 in pancreatic cancer mouse models.TfR expression in pancreatic cancer cell lines (AsPC-1, BxPC-3, MIAPaCa-2 was evaluated by immunofluorescence staining. 111In-labeled anti-TfR antibodies (TSP-A01, TSP-A02 were evaluated in vitro by cell binding assay with the three cell lines and by competitive inhibition assay with MIAPaCa-2. In vivo biodistribution was evaluated in mice bearing BxPC-3 and MIAPaCa-2 xenografts. Tumor volumes of BxPC-3 and MIAPaCa-2 were sequentially measured after 90Y-TSP-A01 injection and histological analysis of tumors was conducted.MIAPaCa-2 cells showed the highest TfR expression, followed by AsPC-1 and BxPC-3 cells. 111In-TSP-A01 and 111In-TSP-A02 bound specifically to the three cell lines according to TfR expression. The dissociation constants for TSP-A01, DOTA-TSP-A01, TSP-A02, and DOTA-TSP-A02 were 0.22, 0.28, 0.17, and 0.22 nM, respectively. 111In-TSP-A01 was highly accumulated in tumors, especially in MIAPaCa-2, but this was not true of 111In-TSP-A02. The absorbed dose for 90Y-TSP-A01 was estimated to be 8.3 Gy/MBq to BxPC-3 and 12.4 Gy/MBq to MIAPaCa-2. MIAPaCa-2 tumors treated with 3.7 MBq of 90Y-TSP-A01 had almost completely disappeared around 3 weeks after injection and regrowth was not observed. Growth of BxPC-3 tumors was inhibited by 3.7 MBq of 90Y-TSP-A01, but the tumor size was not reduced.90Y-TSP-A01 treatment achieved an almost complete response in MIAPaCa-2 tumors, whereas it merely inhibited the growth of BxPC-3 tumors. 90Y-TSP-A01 is a promising RIT agent for pancreatic cancer, although further

  1. Differences in 3D dose distributions due to calculation method of voxel S-values and the influence of image blurring in SPECT.

    Science.gov (United States)

    Pacilio, Massimiliano; Amato, Ernesto; Lanconelli, Nico; Basile, Chiara; Torres, Leonel Alberto; Botta, Francesca; Ferrari, Mahila; Diaz, Nestor Cornejo; Perez, Marco Coca; Fernández, María; Lassmann, Michael; Gil, Alex Vergara; Cremonesi, Marta

    2015-03-07

    This study compares 3D dose distributions obtained with voxel S values (VSVs) for soft tissue, calculated by several methods at their current state-of-the-art, varying the degree of image blurring. The methods were: 1) convolution of Dose Point Kernel (DPK) for water, using a scaling factor method; 2) an analytical model (AM), fitting the deposited energy as a function of the source-target distance; 3) a rescaling method (RSM) based on a set of high-resolution VSVs for each isotope; 4) local energy deposition (LED). VSVs calculated by direct Monte Carlo simulations were assumed as reference. Dose distributions were calculated considering spheroidal clusters with various sizes (251, 1237 and 4139 voxels of 3 mm size), uniformly filled with (131)I, (177)Lu, (188)Re or (90)Y. The activity distributions were blurred with Gaussian filters of various widths (6, 8 and 12 mm). Moreover, 3D-dosimetry was performed for 10 treatments with (90)Y derivatives. Cumulative Dose Volume Histograms (cDVHs) were compared, studying the differences in D95%, D50% or Dmax (ΔD95%, ΔD50% and ΔDmax) and dose profiles.For unblurred spheroidal clusters, ΔD95%, ΔD50% and ΔDmax were mostly within some percents, slightly higher for (177)Lu with DPK (8%) and RSM (12%) and considerably higher for LED (ΔD95% up to 59%). Increasing the blurring, differences decreased and also LED yielded very similar results, but D95% and D50% underestimations between 30-60% and 15-50%, respectively (with respect to 3D-dosimetry with unblurred distributions), were evidenced. Also for clinical images (affected by blurring as well), cDVHs differences for most methods were within few percents, except for slightly higher differences with LED, and almost systematic for dose profiles with DPK (-1.2%), AM (-3.0%) and RSM (4.5%), whereas showed an oscillating trend with LED.The major concern for 3D-dosimetry on clinical SPECT images is more strongly represented by image blurring than by differences among the VSVs

  2. Depth dose distribution in the water for clinical applicators of {sup 90}Sr + {sup 90}Y, with a extrapolation mini chamber; Distribuicao de dose em profundidade na agua para aplicadores clinicos de {sup 90}Sr + {sup 90}Y, com uma mini-camara de extrapolacao

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, Patricia de Lara; Caldas, Linda V.E., E-mail: patrilan@ipen.b, E-mail: lcaldas@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Oliveira, Mercia L., E-mail: mercial@cnen.gov.b [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2009-07-01

    This work determines the depth dose in the water for clinical applicators of {sup 90}Sr + {sup 90}Y, using a extrapolation mini chamber developed at the IPEN, Sao Paulo, Brazil, and different thickness acrylic plates. The obtained results were compared with the international recommendations and were considered satisfactory

  3. Towards tailored radiopeptide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Radojewski, Piotr [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); Dumont, Rebecca [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); UCLA, Department of Radiology, David Geffen School of Medicine, Los Angeles, CA (United States); Marincek, Nicolas; Walter, Martin A. [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Brunner, Philippe; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Briel, Matthias [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland)

    2015-07-15

    Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor. Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving {sup 90}Y-DOTATOC, {sup 177}Lu-DOTATOC or their combination. {sup 90}Y-DOTATOC plus {sup 177}Lu-DOTATOC treatment was associated with longer survival than {sup 90}Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or {sup 177}Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). {sup 177}Lu-DOTATOC was associated with longer survival than {sup 90}Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). {sup 90}Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5 % vs. 4.0 %, p = 0.005) or {sup 177}Lu-DOTATOC (9.5 % vs. 1.4 %, p = 0.002). Renal toxicity was similar among the treatments. Using {sup 90}Y and {sup 177}Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors. (orig.)

  4. New modalities (setting, fractionation) of radioimmunotherapy by {sup 90}Y-ibritumomab tiuxetan ({sup 90}Y zevalin) in first line treatment of follicular type non Hodgkin malignant lymphomas: efficiency, toxicity and personalized dosimetry approach; Nouvelles modalites (consolidation, fractionnement) de radioimmunotherapie par {sup 90}Y-ibritumomab tiuxetan (Zevalin) en traitement de premiere ligne des lymphomes malin non hodgkiniens de type folliculaire: efficacite, toxicite et approche dosimetrique personnalisee

    Energy Technology Data Exchange (ETDEWEB)

    Morschhauser, F

    2008-12-15

    Rationale: radioimmunotherapy (R.I.T.) with {sup 90}Y-ibritumomab tiuxetan ([{sup 90}Y] Zevalin ) is a new treatment option for patients with relapsed/refractory non Hodgkin follicular lymphoma (F.L.). Efficacy increases when Zevalin is used earlier in the disease course. Currently, Zevalin dosage is based on weight and not dosimetry. This most likely results in a wide range of absorbed dose to critical organs and tumor, which in turn translates in unpredictable efficacy and toxicity. Optimizing R.I.T. with [{sup 90}Y] Zevalin will require its use as part of first-line therapy and implementation of patient-specific dosimetry methods in clinical trials. Objectives and methods: we have consecutively studied 2 new modalities of using Zevalin in first line therapy of F.L.. First, we conducted an international, randomized, phase 3 trial to evaluate the efficacy and safety of consolidation with Zevalin(15 MBq/Kg) in patients with advanced-stage F.L. achieving at least a partial response after induction immuno chemotherapy. A second approach consisted of evaluating a fractionated schedule with 2 doses of Zevalin (11.1 MBq/kg each), 9 to 13 weeks apart, as front line therapy in F.L. patients with high tumor burden. As part of this second approach, we designed a refined imaging-based (planar and 3-dimensional) dosimetry protocol to improve prediction of dose efficacy and toxicity after each dose of zevalin. Data acquisition was performed in 3 centers (Lille, Nantes and Manchester) while data treatment and specific dose calculations for major organ, tumor masses and bone marrow were centralized. Conclusion: Consolidation of first remission with {sup 90}Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging P.F.S. by 2 years and resulting in high P.R.-to-C.R. conversion rates regardless of type of first-line induction treatment. Preliminary data show the feasibility of front line fractionated R.I.T. with

  5. Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: results of a phase II study with {sup 90}Y-labeled biotin

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, Giovanni; De Cicco, Concetta; Carbone, Giuseppe; Pacifici, Monica [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Ferrari, Mahila E.; Cremonesi, Marta; Di Dia, Amalia [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Pagani, Gianmatteo; Galimberti, Viviana; Luini, Alberto [European Institute of Oncology, Division of Senology, Milan (Italy); Leonardi, Maria Cristina; Ferrari, Annamaria; Orecchia, Roberto [European Institute of Oncology, Division of Radiotherapy, Milan (Italy); De Santis, Rita [Sigma-Tau SpA R and D, Rome (Italy); Zurrida, Stefano [European Institute of Oncology, Division of Senology, Milan (Italy); University of Milan School of Medicine, Milan (Italy); Veronesi, Umberto [European Institute of Oncology, Scientific Director, Milan (Italy)

    2010-02-15

    External beam radiotherapy (EBRT) after conservative surgery for early breast cancer requires 5-7 weeks. For elderly patients and those distant from an RT center, attending for EBRT may be difficult or impossible. We investigated local toxicity, cosmetic outcomes, and quality of life in a new breast irradiation technique - intraoperative avidination for radionuclide therapy (IART) - in which avidin is administered to the tumor bed and {sup 90}Y-labelled biotin later administered intravenously to bind the avidin and provide irradiation. Reduced duration EBRT (40 Gy) is given subsequently. After surgery, 50 (ten patients), 100 (15 patients) or 150 mg (ten patients) of avidin was injected into the tumor bed. After 12-24 h, 3.7 GBq {sup 90}Y-biotin (beta source for therapeutic effect) plus 185 MBq {sup 111}In-biotin (gamma source for imaging and dosimetry) was infused slowly. Whole-body scintigraphy and SPECT/CT images were taken for up to 30 h. Shortened EBRT started 4 weeks later. Local toxicity was assessed by RTOG scale; quality of life was assessed by EORTC QOL-30. Of 35 patients recruited (mean age 63 years; range 42-74) 32 received IART plus EBRT. 100 mg avidin provided 19.5 {+-} 4.0 Gy to the tumor bed and was considered the optimum dose. No side-effects of avidin or {sup 90}Y-biotin occurred, with no hematological or local toxicity. Local G3 toxicity occurred in 3/32 patients during EBRT. IART plus EBRT was well accepted, with good cosmetic outcomes and maintained quality of life. IART plus reduced EBRT can accelerate irradiation after conservative breast surgery. (orig.)

  6. {sup 90}Y microsphere treatment of unresectable liver metastases: changes in {sup 18}F-FDG uptake and tumour size on PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Bienert, Maren [University of Pittsburgh Medical Center (UPMC), Department of Radiology, Pittsburgh, PA (United States); Charite-University Medicine Berlin, Department of Nuclear Medicine, Berlin (Germany); McCook, Barry; Sheetz, Mike; Tutor, Cecilia; Amesur, Nikhil; Avril, Norbert [University of Pittsburgh Medical Center (UPMC), Department of Radiology, Pittsburgh, PA (United States); Carr, Brian I.; Geller, David A. [University of Pittsburgh Medical Center (UPMC), Department of Surgery, Pittsburgh, PA (United States)

    2005-07-01

    The intra-arterial administration of {sup 90}Y microspheres is a new palliative treatment option for unresectable liver metastases. The aim of this study was to quantitatively assess changes in FDG uptake and tumour size following {sup 90}Y microsphere treatment (SIR-Spheres) using {sup 18}F-fluorodeoxyglucose (FDG) PET/CT imaging. Five patients with unresectable liver metastases who had failed multiple prior chemotherapy regimens received seven {sup 90}Y microsphere treatments to a single liver lobe. All patients underwent a baseline PET/CT scan prior to treatment, as well as up to four follow-up PET/CT scans. The tumour area of 30 liver metastases was measured on CT and the FDG uptake was semiquantitatively assessed by calculation of standardised uptake values (SUVs). A total of 18 FDG-PET/CT scans were performed. The SUVs in the 30 treated liver metastases decreased from 6.5{+-}2.3 at baseline to 4.2{+-}1.8 after the first follow-up PET/CT scan (p=0.001). In contrast, the SUVs of untreated metastases increased slightly from 7.2{+-}2.3 to 8.0{+-}0.8. There was no difference in FDG uptake in treated versus untreated normal liver tissue. Using a previously defined threshold of 20% decrease in SUV from baseline to determine response, 20 out of 30 liver metastases were considered to have responded at the first follow-up PET/CT scan approximately 1 month after treatment. In these metastases, the SUV decreased by 47{+-}12%, compared with a slight increase by 5.9{+-}19% in ten non-responding metastases (p=0.0001). The changes in tumour size did not correlate with changes in FDG uptake. On the first follow-up PET/CT scan, the tumour area on CT increased by 3.1{+-}57% in treated metastases compared with 23.3{+-}32% in untreated metastases. A wide range of post-treatment changes of target lesions was observed on CT, including an increase in the size of hypodense lesions, necrotic features and complete resolution of CT abnormalities. The metabolic information obtained from

  7. Pyclen Tri-n-butylphosphonate Ester as Potential Chelator for Targeted Radiotherapy: From Yttrium(III) Complexation to (90)Y Radiolabeling.

    Science.gov (United States)

    Le Fur, Mariane; Beyler, Maryline; Lepareur, Nicolas; Fougère, Olivier; Platas-Iglesias, Carlos; Rousseaux, Olivier; Tripier, Raphaël

    2016-08-15

    The Y(3+) complex of PCTMB, the tri-n-butyl phosphonate ester of pyclen (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene), was synthesized as well as its Ho(3+) and Lu(3+) analogues. X-ray diffraction analyses revealed isomorphous dimeric M2(PCTMB)2·9H2O (M = Y, Ho, Lu) structures that crystallize in the centrosymmetric P1̅ triclinic space group. (1)H NMR and UV studies in aqueous solutions indicated that Y(3+) complexation is fast, being quantitative in 167 min at pH 3.8 and in 13 min at pH 5.5 (25 °C, acetate buffer, I = 0.150 M, [Y(3+)] = [PCTMB] = 0.2 mM). (1)H NMR DOSY and photon correlation spectroscopy experiments evidenced the formation of aggregates in chloroform with a bimodal distribution that changes slightly with concentration (11-24 and 240-258 nm). The behavior of the acid-assisted dissociation of the complex of Y(3+) with PCTMB was studied under pseudo-first-order conditions, and the half-life of the [Y(PCTMB)] complex in 0.5 M HCl at 25 °C was found to be 37 min, a value that decreases to 2.6 min in 5 M HCl. The Y(3+) complex of PCTMB is thermodynamically very stable, with a stability constant of log KY-PCTMB = 19.49 and pY = 16.7 measured by potentiometry. (90)Y complexation studies revealed fast radiolabeling kinetics; optimal radiolabeling conditions were obtained for (90)Y in acetate medium, PCTMB at 10(-4) to 10(-2) M in acetate buffer pH = 4.75, 15 min at 45-60 °C. In vitro stability studies in human serum showed that [(90)Y(PCTMB)] is quite stable, with about 90% of the activity still in the form of the radiotracer at 24 h and 80% from 48 h to 72 h. A comparison with other ligands such as PCTA, DOTA, and DTPA already used for in vivo application shows that [(90)Y(PCTMB)] is an interesting lipophilic and neutral analogue of these reference chelates for therapeutic applications in aqueous and nonaqueous media.

  8. Preparation and evaluation of {sup 89}Zr-Zevalin for monitoring of {sup 90}Y-Zevalin biodistribution with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Perk, Lars R.; Stigter-van Walsum, M.; Vosjan, Maria J.W.D. [VU University Medical Centre, Department of Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, P.O. Box 7057, Amsterdam (Netherlands); Visser, Otto J.; Huijgens, Peter C. [VU University Medical Centre, Department of Hematology, Amsterdam (Netherlands); Visser, Gerard W.M. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Zijlstra, Josee M. [VU University Medical Centre, Department of Hematology, Amsterdam (Netherlands); VU University Medical Centre, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Dongen, Guus A.M.S. van [VU University Medical Centre, Department of Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Centre, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands)

    2006-11-15

    To evaluate whether {sup 89}Zr can be used as a PET surrogate label for quantification of {sup 90}Y-ibritumomab tiuxetan ({sup 90}Y-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy. Zevalin was labelled with {sup 89}Zr by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of {sup 89}Zr-Zevalin and {sup 88}Y-Zevalin (as a substitute for {sup 90}Y), samples were incubated in human serum at 37 C up to 6 days. Biodistribution of {sup 89}Zr-Zevalin and {sup 88}Y-Zevalin was assessed at 24, 48, 72 and 144 h p.i. by co-injection in nude mice bearing the non-Hodgkin's lymphoma (NHL) xenograft line Ramos. The clinical performance of {sup 89}Zr-Zevalin-PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone [{sup 18}F]FDG-PET 2 weeks previously. Modification of Zevalin with N-sucDf resulted in an N-sucDf-to-antibody molar ratio of 0.83{+-}0.04. After radiolabelling and purification, the radiochemical purity and immunoreactivity of {sup 89}Zr-Zevalin always exceeded 95% and 80%, respectively. {sup 89}Zr-Zevalin showed the same stability in serum as {sup 88}Y-Zevalin, with a radiochemical purity >95% during a period of 6 days. The co-injected {sup 89}Zr-Zevalin and {sup 88}Y-Zevalin conjugates showed a very similar biodistribution, except for liver and bone accumulation at 72 and 144 h p.i., which was significantly higher for {sup 89}Zr than for {sup 88}Y. PET images obtained after injection of {sup 89}Zr-Zevalin showed clear targeting of all known tumour lesions. {sup 89}Zr-Zevalin and {sup 88}Y-Zevalin showed a very similar biodistribution in mice, implying that {sup 89}Zr-Zevalin-PET might be well suited for prediction of {sup 90}Y-Zevalin biodistribution in a myeloablative setting. (orig.)

  9. (Depth-dose curves of the beta reference fields (147)Pm, (85)Kr and (90)Sr/(90)Y produced by the beta secondary standard BSS2.

    Science.gov (United States)

    Brunzendorf, Jens

    2012-08-01

    The most common reference fields in beta dosimetry are the ISO 6980 series 1 radiation fields produced by the beta secondary standard BSS2 and its predecessor BSS. These reference fields require sealed beta radiation sources ((147)Pm, (85)Kr or (90)Sr/(90)Y) in combination with a source-specific beam-flattening filter, and are defined only at a given distance from the source. Every radiation sources shipped with the BSS2 is sold with a calibration certificate of the Physikalisch-Technische Bundesanstalt. The calibration workflow also comprises regular depth-dose measurements. This work publishes complete depth-dose curves of the series 1 sources (147)Pm, (85)Kr and (90)Sr/(90)Y in ICRU tissue up to a depth of 11 mm,when all electrons are stopped. For this purpose, the individual depth-dose curves of all BSS2 sources calibrated so far have been determined, i.e. the complete datasets of all BSS2 beta sources have been re-evaluated. It includes 191 depth-dose curves of 116 different sources comprising more than 2200 data points in total. Appropriate analytical representations of the nuclide-specific depth-dose curves are provided for the first time.

  10. Radioimmunotherapy with {sup 131}I-Rituximab in a Patient with Diffuse Large B-Cell Lymphoma Relapsed After Treatment with {sup 90}Y-Ibritumomab Tiuxetan

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Geon Wook; Kang, Hye Jin; Shin, Dongyeop; Gu, Ha Ra; Choi, Hong Seok; Lim, Sang Moo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2013-12-15

    We report a case that demonstrates the efficacy of radioimmunotherapy (RIT) with radioiodinated rituximab ({sup 131}I-rituximab) for relapsed diffuse large B-cell lymphoma (DLBCL). A 79-year-old male patient with DLBCL initially achieved a complete response (CR) after six cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. However, the lymphoma relapsed 20 months later. Although the patient had achieved a second and a third CR after two cycles of {sup 90}Y-ibritumomab tiuxetan, he experienced a third relapse approximately 3 years later. Between March and June 2011, the patient received three cycles of {sup 131}I-rituximab. Although he had achieved partial response after the second cycle, the disease progressed after the third cycle, and the total progression. Free survival was thus 5 months. The patient suffered only relatively mild toxicity (grade 1 thrombocytopenia) during treatment. RIT with {sup 131}I-rituximab is therefore potentially effective in patients with relapsed DLBCL, even after the failure of {sup 90}Y-ibritumomab tiuxetan therapy.

  11. Dosimetry analysis of distribution radial dose profiles of {sup 90}Sr + {sup 90}Y beta therapy applicators using the MCNP-4C code and radio chromium films; Analise dosimetrica de perfis de distribuicoes radiais de doses relativas de um aplicador de betaterapia de {sup 90}Sr + {sup 90}Y utilizando o codigo MCNP-4C e filmes radiocromicos

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, T.S.; Yoriyaz, H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Fernandes, M.A.R. [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Fac. de Medicina. Servico de Radioterapia; Louzada, M.J.Q. [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Aracatuba, SP (Brazil). Curso de Medicina Veterinaria

    2010-07-01

    Although they are no longer manufactured, the applicators of {sup 90}Sr +{sup 90}Y acquired in the decades of 1990 are still in use, by having half-life of 28.5 years. These applicators have calibration certificate given by their manufacturers, where few have been recalibrated. Thus it becomes necessary to accomplish thorough dosimetry of these applicators. This paper presents a dosimetric analysis distribution radial dose profiles for emitted by an {sup 90}Sr+{sup 90}Y beta therapy applicator, using the MCNP-4C code to simulate the distribution radial dose profiles and radiochromium films to get them experimentally . The results with the simulated values were compared with the results of experimental measurements, where both curves show similar behavior, which may validate the use of MCNP-4C and radiochromium films for this type of dosimetry. (author)

  12. Dosimetry analysis of distributions radials dose profiles of {sup 90}Sr + {sup 90}Y beta therapy applicators using the MCNP-4C code and radio chromium films; Analise dosimetrica de perfis de distribuicoes radias de doses relativas de um aplicador de betaterapia de {sup 90}Sr + {sup 90}Y utilizando o codigo MCNP-4C e filmes radiocromicos

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, Talita S.; Yoriyaz, Helio [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Fernandes, Marco A.R., E-mail: tasallesc@gmail.co [UNESP, Botucatu, SP (Brazil). Faculdade de Medicina. Servico de Radioterapia; Louzada, Mario J.Q. [UNESP, Aracatuba, SP (Brazil). Curso de Medicina Veterinaria

    2011-07-01

    Although they are no longer manufactured, the applicators of {sup 90}Sr + {sup 90}Y acquired in the decades of 1990 are still in use, by having half-life of 28.5 years. These applicators have calibration certificate given by their manufacturers, where few have been re calibrated. Thus it becomes necessary to accomplish thorough dosimetry of these applicators. This paper presents a dosimetric analysis distribution radial dose profiles for emitted by an {sup 90}Sr + {sup 90}Y beta therapy applicator, using the MCNP-4C code to simulate the distribution radial dose profiles and radio chromium films to get them experimentally . The results with the simulated values were compared with the results of experimental measurements, where both curves show similar behavior, which may validate the use of MCNP-4C and radio chromium films for this type of dosimetry. (author)

  13. Calibration of {sup 90}Sr+{sup 90}Y chemical applicators using a mini extrapolation chamber as reference system;Calibracao de aplicadores clinicos de {sup 90}Sr+{sup 90}Y utilizando uma mini-camera de extrapolacao como sistema de referencia

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, Patricia L.; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Oliveira, Mercia L. [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2009-07-01

    {sup 90}Sr + {sup 90}Y clinical applicators are beta radiation sources utilized in several radiotherapy Brazilian clinics, although don't be more manufactured. These sources are employed in brachytherapy procedures for the treatment of superficial lesions of skin and eyes. International recommendations and previous works determine that dermatological and ophthalmic applicators shall be calibrated periodically, and one of the methods for their calibration consists of the use of an extrapolation chamber. In this work, a method of calibration of {sup 90}Sr + {sup 90}Y clinical applicators was applied using a mini-extrapolation chamber of plane window, developed at the Calibration Laboratory at IPEN, as a reference system. The results obtained were considered satisfactory, when compared with the results given in the calibration certificates of the sources. (author)

  14. The prognostic value of functional tumor volume and total lesion glycolysis in patients with colorectal cancer liver metastases undergoing {sup 90}Y selective internal radiation therapy plus chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gulec, Seza A.; Suthar, Rekha R.; Barot, Tushar C. [Jackson North Medical Center, Florida International University College of Medicine, North Miami Beach, FL (United States); Pennington, Kenneth [Center for Cancer Care, Goshen, IN (United States)

    2011-07-15

    Functional tumor volume (FTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images. These parameters could potentially have clinical value in response to treatment evaluation and disease prognostication. The objectives of this study were to investigate the relationship between functional tumor parameters (FTV and TLG) and clinical outcomes in patients with colorectal cancer liver metastases (CRCLM) undergoing {sup 90}Y-resin microsphere selective internal radiation therapy (SIRT) (SIR-Spheres {sup registered}, Sirtex Medical Limited, Lane Cove, NSW, Australia). FDG PET/CT studies of 20 patients with unresectable CRCLM who underwent {sup 90}Y SIRT under a phase II clinical trial were analyzed. FTV and TLG were calculated using PET VCAR (GE Healthcare, Milwaukee, WI, USA) on pretreatment and 4-week posttreatment scans. The effects of pretreatment and posttreatment functional tumor activity on patient survival were evaluated using Kaplan-Meier survival curves. The median survival in the study group was 14.8 months (range 2.0-27.7 months). The median survival for patients with pretreatment FTV values of above and below 200 cc were 11.2 and 26.9 months, respectively (p < 0.05). The median survival for patients with 4-week posttreatment FTV values of above and below 30 cc were 10.9 and 26.9 months, respectively (p < 0.05). The median survival for patients with pretreatment TLG values of above and below 600 g were 11.2 and 26.9 months, respectively (p < 0.05). The median survival for patients with 4-week posttreatment TLG values of above and below 100 g were 10.9 and 26.9 months, respectively (p < 0.05). Pretreatment and posttreatment FTV and TLG showed very strong association with survival. These values can be useful quantitative criteria for patient selection and disease prognostication when {sup 90}Y SIRT is contemplated in patients with CRCLM. (orig.)

  15. A multicentre comparison of quantitative {sup 90}Y PET/CT for dosimetric purposes after radioembolization with resin microspheres. The QUEST phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Willowson, Kathy P. [University of Sydney, Institute of Medical Physics, School of Physics, Sydney, NSW (Australia); Tapner, Michael [Sirtex, North Sydney, NSW (Australia); Bailey, Dale L. [Royal North Shore Hospital, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Faculty of Health Sciences, Lidcombe (Australia); Collaboration: The QUEST Investigator Team

    2015-07-15

    To investigate and compare the quantitative accuracy of {sup 90}Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of {sup 90}Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter <20 mm. For spheres >20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Current generation ToF scanners can consistently reconstruct {sup 90}Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and

  16. Matched pairs dosimetry: {sup 124}I/{sup 131}I metaiodobenzylguanidine and {sup 124}I/{sup 131}I and {sup 86}Y/{sup 90}Y antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Fanti, Stefano [Policlinico S.Orsola-Malpighi and University of Bologna, Bologna (Italy); Chiti, Arturo; Pepe, Giovanna; Antunovic, Lidija [IRCCS Humanitas, Nuclear Medicine, Rozzano, MI (Italy); Castellani, Maria Rita; Bombardieri, Emilio [Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan (Italy)

    2011-06-15

    The technological advances in imaging and production of radiopharmaceuticals are driving an innovative way of evaluating the targets for antineoplastic therapies. Besides the use of imaging to better delineate the volume of external beam radiation therapy in oncology, modern imaging techniques are able to identify targets for highly specific medical therapies, using chemotherapeutic drugs and antiangiogenesis molecules. Moreover, radionuclide imaging is able to select targets for radionuclide therapy and to give the way to in vivo dose calculation to target tissues and to critical organs. This contribution reports the main studies published on matched pairs dosimetry with {sup 124}I/{sup 131}I- and {sup 86}Y/{sup 90}Y-labelled radiopharmaceuticals, with an emphasis on metaiodobenzylguanidine (MIBG) and monoclonal antibodies. (orig.)

  17. Individualized dosimetry-based activity reduction of {sup 90}Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Binnebeek, Sofie van; Baete, Kristof; Vanbilloen, Bert; Terwinghe, Christelle; Mortelmans, Luc [University Hospitals Leuven, Nuclear Medicine, Leuven (Belgium); KU Leuven, Department of Imaging and Pathology, Leuven (Belgium); Koole, Michel [University Medical Centre Groningen, Department of Nuclear Medicine, Groningen (Netherlands); Mottaghy, Felix M. [University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Clement, Paul M. [University Hospitals Leuven, Medical Oncology, Leuven (Belgium); KU Leuven, Laboratory of Experimental Oncology, Leuven (Belgium); Haustermans, Karin [University Hospitals Leuven, Radiation Oncology, Leuven (Belgium); KU Leuven, Department of Oncology, Leuven (Belgium); Cutsem, Eric van; Verslype, Chris [KU Leuven, Department of Oncology, Leuven (Belgium); University Hospitals Leuven, Division of Digestive Oncology, Leuven (Belgium); Verbruggen, Alfons [KU Leuven, Laboratory for Radiopharmacy, Leuven (Belgium); Bogaerts, Kris [KU Leuven, Division of Public Health and Primary Care (I-Biostat), Leuven (Belgium); Deroose, Christophe M. [University Hospitals Leuven, Nuclear Medicine, Leuven (Belgium); KU Leuven, Department of Imaging and Pathology, Leuven (Belgium); UZ Leuven, Nuclear Medicine, Leuven (Belgium)

    2014-06-15

    Assessment of kidney function evolution after {sup 90}Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney. In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq {sup 111}In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using {sup 51}Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL). Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33 % was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT. Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for {sup 90}Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity. (orig.)

  18. Does the pretherapeutic tumor SUV in 68Ga DOTATOC PET predict the absorbed dose of 177Lu octreotate?

    Science.gov (United States)

    Ezziddin, Samer; Lohmar, Jonas; Yong-Hing, Charlotte J; Sabet, Amir; Ahmadzadehfar, Hojjat; Kukuk, Guido; Biersack, Hans-Jürgen; Guhlke, Stefan; Reichmann, Karl

    2012-06-01

    Selection of candidates for peptide receptor radionuclide therapy (PRRT) is increasingly based on receptor positron emission tomography (PET) imaging, including the common tracer 68Ga DOTATOC. However, no studies have yet compared standardized uptake values (SUVs) and absorbed doses in this field. We retrospectively analyzed a consecutive cohort of 21 patients with 61 evaluable tumor lesions undergoing both pretherapeutic 68Ga DOTATOC-PET/CT (Biograph Duo [Siemens Medical Solutions, Erlangen, Germany]; PET acquisition, 75.3 ± 15.4 minutes postinjection; 117.3 ± 33.9 MBq 68Ga DOTATOC) and PRRT with Lu octreotate (7.47 ± 1.39 GBq; intratherapeutic tumor dosimetry with serial whole-body scans; 1, 2, and 4 days postinjection) at our institution. SUVs were compared with the tumor-absorbed doses per injected activity (D/A0) of the subsequent first treatment cycle. The correlation of SUV and D/A0 was r = 0.72 (SUVmean) and r = 0.71 (SUVmax), both P 15; SUVmax >25) resulted in high D/A0 (>10 Gy/GBq) in 66.7% to 70.8% and low D/A0 (<5 Gy/GBq) in only 8.3% to 12.5% on subsequent PRRT. The mentioned low D/A0 range, on the other hand, was achieved by all lesions with SUVmean <7 or SUVmax <9. Somatostatin receptor PET imaging may predict tumor-absorbed doses. The ability to indicate insufficient target irradiation by a low SUV could aid in selection of appropriate candidates for PRRT. However, larger series are needed to confirm and validate these initial findings.

  19. Investigation of models with temporal and spatial interference in image based dosimetry of {sup 177}Lu-labelled radioligand therapies

    Energy Technology Data Exchange (ETDEWEB)

    Delker, Andreas

    2016-07-12

    In targeted radio ligand therapy determination of the regional distribution of the radiation dose is mandatory for the development of therapy strategies which aim for maximizing the therapeutic effect on the tumor, while reducing radiation exposure to healthy tissue. For this purpose, after administration of the therapeutic agent, sequential measurements with a scintillation camera are required to quantitatively assess the kinetics and distribution of the radiopharmaceutical in the body. To improve the accuracy and robustness of existing dosimetric concepts, the kinetic of Lu-177-DOTATATE, a radiopharmaceutical for the treatment of patients with neuroendocrine tumors, was examined in depth. Subsequently, the findings from this study were used to carry out the first image-based dosimetry for the new active substance Lu-177-PSMA, a radiopharmaceutical for the treatment of patients with metastatic prostate cancer. Due to the specific distribution pattern of this ligand, overlay effects in the 2-dimensional (2-D) planar projection were observed. Therefore a quantitative 3-dimensional (3-D) SPECT imaging technique was established and optimized for dosimetry. To characterize the dynamics of Lu-177-DOTATATE, whole-body planar projections of 105 patients were recorded at 1, 24, 48 and 72 h after injection. Furthermore, the first hour beginning with the start of the therapeutic agent administration was measured in 12 time frames with duration of 5 min each. An optimal dose model was introduced for the kidneys, for those being a risk organ in this therapy, which consisted of three phases: a linear increase of tracer accumulation during infusion, followed by a 2-phase model being described by a bi-exponential decline. This full data model served as a basis for comparison with reduced data models based on mono-exponentials which made use of all four (at 1, 24, 48 and 72 h after injection) or the last three whole-body scintigraphies. The established quantitative 3-D SPECT technique presented a sufficient recovery of known activity in medium size spherical objects with more than 30 mm diameter (approx. 80 % and above), although a significant underestimation of activity was observed in smaller spheres. With this 3-D dosimetry an estimated dose of 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq) and 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq) could be reported. The dose to the salivary glands, being assessed with 2-D dosimetry, was 5.1 ± 1.8 Gy (1.4 Gy/GBq). By combining all available 2-D- and 3-D-dosimetric data the absorbed dose of the bone marrow was estimated with 44 ± 19 mGy (0.012 Gy/GBq). Kinetic analyses of the renal uptake revealed a fast and slow washout phase. Thereby, the slow phase component was found to be responsible to cause the major fraction of the absorbed dose (98.9 %). Although the fast phase did not contribute substantially to the estimated renal dose, it had a high likelihood of interfering with the slow phase within the initial hours after injection. The unexpected dose underestimation which was observed with dosimetry calculations relying on these early time points, such as the reduced data model including the 1h measurement, could finally be explained with this discovery. These underestimations could lead to an over dosage of the therapy activity and thus to a critical radiation exposure to healthy tissue. By omitting this influenced measurement point and the solely use of the last three data points in the reduced data model, the dose delivering phase could be accurately displayed. With the insights gained in this study we were therefore able to develop a dosimetry model and workflow with increased robustness and higher confidence in the reported dose estimates, which at the same time relied on fewer measurements and therefore provided a significant reduction of work load for the staff and overall burden for the patients. This model was then applied in the dose assessment of the new radiopharmaceutical Lu-177-PSMA to avoid the above reported temporal interference effects. Fur

  20. Favourable outcomes of {sup 177}Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Hofman, Michael S.; Kong, Grace; Akhurst, Timothy; Eu, Peter [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Peter MacCallum Cancer Centre, Neuroendocrine Tumour Service, Melbourne (Australia); Michael, Michael [University of Medicine, Department of Medicine, Melbourne (Australia); Peter MacCallum Cancer Centre, Division of Cancer Medicine, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Zannino, Diana [Peter MacCallum Cancer Centre, Biostatistics and Clinical Trials, Melbourne (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Peter MacCallum Cancer Centre, Neuroendocrine Tumour Service, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia)

    2014-09-11

    Increased glycolytic activity on FDG PET/CT defines a subgroup of patients with metastatic gastroenteropancreatic neuroendocrine tumour (NET) with a poor prognosis. A limited range of systemic treatment options exist for more aggressive NET. The role of peptide receptor chemoradionuclide therapy (PRCRT) in such patients is, however, unclear. This retrospective study assessed the outcomes of patients with FDG-avid NET treated with PRCRT. Clinical, biochemical and imaging response was assessed after completion of induction treatment of PRCRT with 5-fluorouracil in 52 patients selected for treatment on the basis of somatostatin-receptor imaging without spatially discordant FDG-avid disease. Of the cohort, 67 % had received prior chemotherapy. Overall survival (OS) and progression-free survival (PFS) were also analysed. PRCRT was well tolerated with negligible grade 3/4 toxicities. After a median follow-up period of 36 months, the median OS was not achieved with a median PFS of 48 months. At 3 months after completion of PRCRT 2 % of patients showed a complete anatomical response, 28 % a partial response, 68 % stable disease, and only 2 % progression. On FDG PET/CT, 27 % achieved a complete metabolic response during the follow-up period. A biochemical response (>25 % fall in chromogranin-A levels) was seen in 45 %. PRCRT is an effective treatment in patients with FDG-avid NET, even in patients who have failed conventional therapies. Given apparently higher response rates than with alternative therapeutic options and low toxicity, further research is needed to establish whether PRCRT should be used as a first-line treatment modality in this patient population. (orig.)

  1. Radioembolization of hepatocarcinoma with {sup 90}Y glass microspheres: development of an individualized treatment planning strategy based on dosimetry and radiobiology

    Energy Technology Data Exchange (ETDEWEB)

    Chiesa, C.; Maccauro, M.; Aliberti, G.; Padovano, B.; Seregni, E.; Crippa, F. [Foundation IRCCS Istituto Nazionale Tumori, Nuclear Medicine Division, Milan (Italy); Mira, M.; Negri, A. [University of Milan, Postgraduate Health Physics School, Milan (Italy); Spreafico, C.; Morosi, C.; Civelli, E.; Lanocita, R.; Marchiano, A. [Foundation IRCCS Istituto Nazionale Tumori, Radiology 2, Milan (Italy); Romito, R.; Sposito, C.; Bhoori, S.; Facciorusso, A.; Mazzaferro, V. [Foundation IRCCS Istituto Nazionale Tumori, Surgery 1, Milan (Italy); Camerini, T. [Foundation IRCCS Istituto Nazionale Tumori, Scientific Direction, Milan (Italy); Carrara, M. [Foundation IRCCS Istituto Nazionale Tumori, Health Physics, Milan (Italy); Pellizzari, S. [University La Sapienza, Engineering Faculty, Rome (Italy); Migliorisi, M. [Foundation IRCCS Istituto Nazionale Tumori, Nuclear Medicine Division, Milan (Italy); Foundation IRCCS Istituto Nazionale Tumori, Clinical Engineering, Milan (Italy); De Nile, M.C. [University of Pavia, Physics Faculty, Pavia, Lombardy (Italy)

    2015-10-15

    The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an individualized treatment planning strategy based on {sup 99m}Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. We performed retrospective dosimetry of the standard TheraSphere registered treatment on 52 intermediate (n = 17) and advanced (i.e. portal vein thrombosis, n = 35) hepatocarcinoma patients with tumour burden < 50 % and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on {sup 99m}Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of {sup 99m}Tc-MAA and {sup 90}Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS trademark by Philips). STRATOS trademark absorbed dose calculation was validated for {sup 90}Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BED{sub ave}) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were

  2. 3D inpatient dose reconstruction from the PET-CT imaging of {sup 90}Y microspheres for metastatic cancer to the liver: Feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Fourkal, E.; Veltchev, I.; Lin, M.; Meyer, J. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 (United States); Koren, S. [Department of Radiation Oncology, Beth Israel Comprehensive Cancer Center, New York, New York 10011 (United States); Doss, M.; Yu, J. Q. [Department of Diagnostic Imaging, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 (United States)

    2013-08-15

    Purpose: The introduction of radioembolization with microspheres represents a significant step forward in the treatment of patients with metastatic disease to the liver. This technique uses semiempirical formulae based on body surface area or liver and target volumes to calculate the required total activity for a given patient. However, this treatment modality lacks extremely important information, which is the three-dimensional (3D) dose delivered by microspheres to different organs after their administration. The absence of this information dramatically limits the clinical efficacy of this modality, specifically the predictive power of the treatment. Therefore, the aim of this study is to develop a 3D dose calculation technique that is based on the PET imaging of the infused microspheres.Methods: The Fluka Monte Carlo code was used to calculate the voxel dose kernel for {sup 90}Y source with voxel size equal to that of the PET scan. The measured PET activity distribution was converted to total activity distribution for the subsequent convolution with the voxel dose kernel to obtain the 3D dose distribution. In addition, dose-volume histograms were generated to analyze the dose to the tumor and critical structures.Results: The 3D inpatient dose distribution can be reconstructed from the PET data of a patient scanned after the infusion of microspheres. A total of seven patients have been analyzed so far using the proposed reconstruction method. Four patients underwent treatment with SIR-Spheres for liver metastases from colorectal cancer and three patients were treated with Therasphere for hepatocellular cancer. A total of 14 target tumors were contoured on post-treatment PET-CT scans for dosimetric evaluation. Mean prescription activity was 1.7 GBq (range: 0.58–3.8 GBq). The resulting mean maximum measured dose to targets was 167 Gy (range: 71–311 Gy). Mean minimum dose to 70% of target (D70) was 68 Gy (range: 25–155 Gy). Mean minimum dose to 90% of target

  3. ANÁLISIS COMPARATIVO DE LOS EFECTOS AGUDOS DE SESIONES DE ENTRENAMIENTO DE FUERZA CON CARGAS DEL 90 Y 30% 1 RM.

    Directory of Open Access Journals (Sweden)

    Jorge Dopico Calvo

    2010-10-01

    Full Text Available En una medición inicial (Pretest se obtuvo la 1RM de 23 sujetos masculinos en el ejercicio press banca, así como la potencia y fuerza media aplicada al 90 y 30% de 1RM (PMED90, FMED90, PMED30, FMED 30. Posteriormente 11 sujetos (Gr90 llevaron a cabo 2 sesiones de entrenamiento con cargas del 90%, mientras los 12 sujetos restantes (Gr30 lo hacían con cargas del 30%. Inmediatamente finalizada cada una de las sesiones se valoraba nuevamente PMED90, FMED90, PMED30, FMED30. Una semana después de la finalización de los entrenamientos se efectuó un Postest. Los resultados mostraron una mejora estadísticamente significativa del rendimiento de Gr30 al final de cada una de las sesiones de entrenamiento, respecto a Pretest y Postest, con el 90% de 1RM, mientras que Gr90 obtuvo mejoras significativas con el 30% respecto a Pretest, pero no respecto a Postest.
    PALABRAS CLAVE: fuerza, potencia, medición, efecto agudo.

  4. Preliminary Study on Hydrogen Permeation and Stability of BaCe0.90Y0.10O3-δ Membrane under Asymmetric Atm osphere

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@High-temperature proton conductors (HTPC) have been extensively studied since I wahara et al?1? reported protonic conduction in SrCeO3-based oxid es. Later, the BaCeO3-based oxides, such as BaCe0.90Yb0.10O3- d (BCYb10) and BaCe0.90Y0.10-O3-d (BCY10), we re fou nd to show higher conductivity?2?. High electronic and protonic conducti vity makes BCY10 a potential membrane for hydrogen separation?3?. Thin f ilms with high density, most probably made by sequential coating on porous subst rates, are imperative in order to promote hydrogen permeation flux?4?. T his makes it more necessary for such membranes to be kept stable and unspoilt un der asymmetric hydrogen-permeation atmosphere at elevated temperatures. In this paper, the stability and hydrogen permeation ability of BCY10 membrane are stud ied by XRD, SEM, energy dispersive X-ray (EDX) analysis, H2-TPR process and hydrogen permeation experiment. The results showed that hydrogen cannot permeate through the BCY10 membrane without surface modification, and its surface cannot keep a uniform perovskite structure in the asymmetric atmosphere.

  5. Individual monitoring of internal exposure for nuclear medicine workers in Switzerland.

    Science.gov (United States)

    Baechler, S; Stritt, N; Bochud, F O

    2011-03-01

    Monitoring of internal exposure for nuclear medicine workers requires frequent measurements due to the short physical half-lives of most radionuclides used in this field. The aim of this study was to develop screening measurements performed at the workplace by local staff using standard laboratory instrumentation, to detect whether potential intake has occurred. Such measurements do not enable to determine the committed effective dose, but are adequate to verify that a given threshold is not exceeded. For radioiodine, i.e. (123)I, (124)I, (125)I and (131)I, a calibrated surface contamination monitor is placed in front of the thyroid to detect whether the activity threshold has been exceeded. For radionuclides with very short physical half-lives (≤ 6 h), such as (99m)Tc and those used in positron emission tomography imaging, i.e. (11)C, (15)O, (18)F and (68)Ga, screening procedures consist in performing daily measurements of the ambient dose rate in front of the abdomen. Other gamma emitters used for imaging, i.e. (67)Ga, (111)In and (201)Tl, are measured with a scintillation detector located in front of the thorax. For pure beta emitters, i.e. (90)Y and (169)Er, as well as beta emitters with low-intensity gamma rays, i.e. (153)Sm, (177)Lu, (186)Re and (188)Re, the procedure consists in measuring hand contamination immediately after use. In Switzerland, screening procedures have been adopted by most nuclear medicine services since such measurements enable an acceptable monitoring while taking into account practical and economic considerations.

  6. A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions

    Science.gov (United States)

    Lanconelli, N.; Pacilio, M.; Lo Meo, S.; Botta, F.; Di Dia, A.; Torres Aroche, L. A.; Coca Pérez, M. A.; Cremonesi, M.

    2012-01-01

    The increasing availability of SPECT/CT devices with advanced technology offers the opportunity for the accurate assessment of the radiation dose to the biological target volume during radionuclide therapy. Voxel dosimetry can be performed employing direct Monte Carlo radiation transport simulations, based on both morphological and functional images of the patient. On the other hand, for voxel dosimetry calculations the voxel S value method can be considered an easier approach than patient-specific Monte Carlo simulations, ensuring a good dosimetric accuracy at least for anatomic regions which are characterized by uniform density tissue. However, this approach has been limited because of the lack of tabulated S values for different voxel dimensions and radionuclides. The aim of this work is to provide a free dataset of values which can be used for voxel dosimetry in targeted radionuclide studies. Seven different radionuclides (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, 188Re), and 13 different voxel sizes (2.21, 2.33, 2.4, 3, 3.59, 3.9, 4, 4.42, 4.8, 5, 6, 6.8 and 9.28 mm) are considered. Voxel S values are calculated performing simulations of monochromatic photon and electron sources in two different homogeneous tissues (soft tissue and bone) with DOSXYZnrc code, and weighting the contributions on the basis of the radionuclide emission spectra. The outcomes are validated by comparison with Monte Carlo simulations obtained with other codes (PENELOPE and MCNP4c) performing direct simulation of the radionuclide emission spectra. The differences among the different Monte Carlo codes are of the order of a few per cent when considering the source voxel and the bremsstrahlung tail, whereas the highest differences are observed at a distance close to the maximum continuous slowing down approximation range of electrons. These discrepancies would negligibly affect dosimetric assessments. The dataset of voxel S values can be freely downloaded from the website www.medphys.it.

  7. A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions.

    Science.gov (United States)

    Lanconelli, N; Pacilio, M; Lo Meo, S; Botta, F; Di Dia, A; Aroche, A Torres; Pérez, M A Coca; Cremonesi, M

    2012-01-21

    The increasing availability of SPECT/CT devices with advanced technology offers the opportunity for the accurate assessment of the radiation dose to the biological target volume during radionuclide therapy. Voxel dosimetry can be performed employing direct Monte Carlo radiation transport simulations, based on both morphological and functional images of the patient. On the other hand, for voxel dosimetry calculations the voxel S value method can be considered an easier approach than patient-specific Monte Carlo simulations, ensuring a good dosimetric accuracy at least for anatomic regions which are characterized by uniform density tissue. However, this approach has been limited because of the lack of tabulated S values for different voxel dimensions and radionuclides. The aim of this work is to provide a free dataset of values which can be used for voxel dosimetry in targeted radionuclide studies. Seven different radionuclides (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, 188Re), and 13 different voxel sizes (2.21, 2.33, 2.4, 3, 3.59, 3.9, 4, 4.42, 4.8, 5, 6, 6.8 and 9.28 mm) are considered. Voxel S values are calculated performing simulations of monochromatic photon and electron sources in two different homogeneous tissues (soft tissue and bone) with DOSXYZnrc code, and weighting the contributions on the basis of the radionuclide emission spectra. The outcomes are validated by comparison with Monte Carlo simulations obtained with other codes (PENELOPE and MCNP4c) performing direct simulation of the radionuclide emission spectra. The differences among the different Monte Carlo codes are of the order of a few per cent when considering the source voxel and the bremsstrahlung tail, whereas the highest differences are observed at a distance close to the maximum continuous slowing down approximation range of electrons. These discrepancies would negligibly affect dosimetric assessments. The dataset of voxel S values can be freely downloaded from the website www.medphys.it.

  8. 188Re-SSS/Lipiodol: Development of a Potential Treatment for HCC from Bench to Bedside

    Science.gov (United States)

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-01-01

    Hepatocellular carcinoma (HCC) is the 5th most common tumour worldwide and has a dark prognosis. For nonoperable cases, metabolic radiotherapy with Lipiodol labelled with β-emitters is a promising therapeutic option. The Comprehensive Cancer Centre Eugène Marquis and the National Graduate School of Chemistry of Rennes (ENSCR) have jointly developed a stable and efficient labelling of Lipiodol with rhenium-188 (Eβmax = 2.1 MeV) for the treatment of HCC. The major “milestones” of this development, from the first syntheses to the recent first injection in man, are described. PMID:22518301

  9. (188)Re-SSS/Lipiodol: Development of a Potential Treatment for HCC from Bench to Bedside.

    Science.gov (United States)

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-01-01

    Hepatocellular carcinoma (HCC) is the 5th most common tumour worldwide and has a dark prognosis. For nonoperable cases, metabolic radiotherapy with Lipiodol labelled with β-emitters is a promising therapeutic option. The Comprehensive Cancer Centre Eugène Marquis and the National Graduate School of Chemistry of Rennes (ENSCR) have jointly developed a stable and efficient labelling of Lipiodol with rhenium-188 (E(βmax) = 2.1 MeV) for the treatment of HCC. The major "milestones" of this development, from the first syntheses to the recent first injection in man, are described.

  10. Biodistribution, radiation dosimetry and scouting of {sup 90}Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin's lymphoma using {sup 89}Zr-ibritumomab tiuxetan and PET

    Energy Technology Data Exchange (ETDEWEB)

    Rizvi, Saiyada N.F.; Lingen, Arthur van; Hoekstra, Otto S. [VU University Medical Center, Department of Nuclear Medicine and PET Research, PO Box 7057, Amsterdam (Netherlands); Visser, Otto J.; Zijlstra, Josee M.; Huijgens, Peter C. [VU University Medical Center, Department of Haematology, Amsterdam (Netherlands); Vosjan, Maria J.W.D.; Dongen, Guus A.M.S. van [VU University Medical Center, Department of Otolaryngology and Head and Neck Surgery, Amsterdam (Netherlands); Lubberink, Mark [VU University Medical Center, Department of Nuclear Medicine and PET Research, PO Box 7057, Amsterdam (Netherlands); Uppsala University, and Medical Physics, Uppsala University Hospital, Department of Nuclear Medicine and PET, Uppsala (Sweden)

    2012-03-15

    Positron emission tomography (PET) with {sup 89}Zr-ibritumomab tiuxetan can be used to monitor biodistribution of {sup 90}Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of {sup 90}Y-ibritumomab tiuxetan in humans on the basis of {sup 89}Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of {sup 90}Y-ibritumomab tiuxetan influences biodistribution of {sup 89}Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with {sup 89}Zr-ibritumomab tiuxetan can be used to predict biodistribution of {sup 90}Y-ibritumomab tiuxetan and the dose-limiting organ during therapy. Seven patients with relapsed B-cell non-Hodgkin's lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of {proportional_to}70 MBq {sup 89}Zr-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg {sup 90}Y-ibritumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data. The highest {sup 90}Y absorbed dose was observed in liver (3.2 {+-} 1.8 mGy/MBq) and spleen (2.9 {+-} 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 {+-} 0.04 mGy/MBq, and the effective dose was 0.87 {+-} 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on {sup 89}Zr-ibritumomab tiuxetan images was high (Pearson correlation coefficient r = 0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower (r = 0.75). Biodistribution of {sup 89}Zr-ibritumomab tiuxetan is not influenced by simultaneous

  11. The use of gel dosimetry to measure the 3D dose distribution of a 90Sr/90Y intravascular brachytherapy seed.

    Science.gov (United States)

    Massillon-Jl, G; Minniti, R; Mitch, M G; Maryanski, M J; Soares, C G

    2009-03-21

    Absorbed dose distributions in 3D imparted by a single (90)Sr/(90)Y beta particle seed source of the type used for intravascular brachytherapy were investigated. A polymer gel dosimetry medium was used as a dosemeter and phantom, while a special high-resolution laser CT scanner with a spatial resolution of 100 microm in all dimensions was used to quantify the data. We have measured the radial dose function, g(L)(r), observing that g(L)(r) increases to a maximum value and then decreases as the distance from the seed increases. This is in good agreement with previous data obtained with radiochromic film and thermoluminescent dosemeters (TLDs), even if the TLDs underestimate the dose at distances very close to the seed. Contrary to the measurements, g(L)(r) calculated through Monte Carlo simulations and reported previously steadily decreases without a local maximum as a function of the distance from the seed. At distances less than 1.5 mm, differences of more than 20% are observed between the measurements and the Monte Carlo calculations. This difference could be due to a possible underestimation of the energy absorbed into the seed core and encapsulation in the Monte Carlo simulation, as a consequence of the unknown precise chemical composition of the core and its respective density for this seed. The results suggest that g(L)(r) can be measured very close to the seed with a relative uncertainty of about 1% to 2%. The dose distribution is isotropic only at distances greater than or equal to 2 mm from the seed and is almost symmetric, independent of the depth. This study indicates that polymer gel coupled with the special small format laser CT scanner are valid and accurate methods for measuring the dose distribution at distances close to an intravascular brachytherapy seed.

  12. SU-E-T-02: 90Y Microspheres Dosimetry Calculation with Voxel-S-Value Method: A Simple Use in the Clinic

    Energy Technology Data Exchange (ETDEWEB)

    Maneru, F; Gracia, M; Gallardo, N; Olasolo, J; Fuentemilla, N; Bragado, L; Martin-Albina, M; Lozares, S; Pellejero, S; Miquelez, S; Rubio, A [Complejo Hospitalario de Navarra, Pamplona, Navarra (Spain); Otal, A [Hospital Clinica Benidorm, Benidorm, Alicante (Spain)

    2015-06-15

    Purpose: To present a simple and feasible method of voxel-S-value (VSV) dosimetry calculation for daily clinical use in radioembolization (RE) with {sup 90}Y microspheres. Dose distributions are obtained and visualized over CT images. Methods: Spatial dose distributions and dose in liver and tumor are calculated for RE patients treated with Sirtex Medical miscrospheres at our center. Data obtained from the previous simulation of treatment were the basis for calculations: Tc-99m maggregated albumin SPECT-CT study in a gammacamera (Infinia, General Electric Healthcare.). Attenuation correction and ordered-subsets expectation maximization (OSEM) algorithm were applied.For VSV calculations, both SPECT and CT were exported from the gammacamera workstation and registered with the radiotherapy treatment planning system (Eclipse, Varian Medical systems). Convolution of activity matrix and local dose deposition kernel (S values) was implemented with an in-house developed software based on Python code. The kernel was downloaded from www.medphys.it. Final dose distribution was evaluated with the free software Dicompyler. Results: Liver mean dose is consistent with Partition method calculations (accepted as a good standard). Tumor dose has not been evaluated due to the high dependence on its contouring. Small lesion size, hot spots in health tissue and blurred limits can affect a lot the dose distribution in tumors. Extra work includes: export and import of images and other dicom files, create and calculate a dummy plan of external radiotherapy, convolution calculation and evaluation of the dose distribution with dicompyler. Total time spent is less than 2 hours. Conclusion: VSV calculations do not require any extra appointment or any uncomfortable process for patient. The total process is short enough to carry it out the same day of simulation and to contribute to prescription decisions prior to treatment. Three-dimensional dose knowledge provides much more information than

  13. Clinical impact of {sup 99m}Tc-MAA SPECT/CT-based dosimetry in the radioembolization of liver malignancies with {sup 90}Y-loaded microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Garin, Etienne [Cancer Institute Eugene Marquis, Department of Nuclear Medicine, Rennes (France); University of Rennes 1, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Rolland, Yan [Cancer Institute Eugene Marquis, Department of Medical Imaging, Rennes (France); Laffont, Sophie [University of Rennes 1, Rennes (France); Edeline, Julien [University of Rennes 1, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Cancer Institute Eugene Marquis, Department of Medical Oncology, Rennes (France)

    2016-03-15

    Radioembolization with {sup 90}Y-loaded microspheres is increasingly used in the treatment of primary and secondary liver cancer. Technetium-99 m macroaggregated albumin (MAA) scintigraphy is used as a surrogate of microsphere distribution to assess lung or digestive shunting prior to therapy, based on tumoral targeting and dosimetry. To date, this has been the sole pre-therapeutic tool available for such evaluation. Several dosimetric approaches have been described using both glass and resin microspheres in hepatocellular carcinoma (HCC) and liver metastasis. Given that each product offers different specific activities and numbers of spheres injected, their radiobiological properties are believed to lightly differ. This paper summarizes and discusses the available studies focused on MAA-based dosimetry, particularly concentrating on potential confounding factors like clinical context, tumor size, cirrhosis, previous or concomitant therapy, and product used. In terms of the impact of tumoral dose in HCC, the results were concordant and a response relationship and tumoral threshold dose was clearly identified, especially in studies using glass microspheres. Tumoral dose has also been found to influence survival. The concept of treatment intensification has recently been introduced, yet despite several studies publishing interesting findings on the tumor dose-metastasis relationship, no consensus has been reached, and further clarification is thus required. Nor has the maximal tolerated dose to the liver been well documented, requiring more accurate evaluation. Lung dose was well described, despite recently identified factors influencing its evaluation, requiring further assessment. MAA SPECT/CT dosimetry is accurate in HCC and can now be used in order to achieve a fully customized approach, including treatment intensification. Yet further studies are warranted for the metastasis setting and evaluating the maximal tolerated liver dose. (orig.)

  14. Early post-treatment FDG PET predicts survival after {sup 90}Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Aouf, Anas; Sabet, Amin; Ghamari, Shahab; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Meyer, Carsten; Pieper, Claus C. [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2014-10-29

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with {sup 90}Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent {sup 18}F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUV{sub max}) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p < 0.001) with a median OS of 10 months (95 % CI 3-16) versus 4 months (95 % CI 2-6). Hepatic tumour burden also had significant impact on treatment outcome (p < 0.001) with a median OS of 5 months (95 % CI, 3-7) for patients with >25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using {sup 18}F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  15. Late and very late catch-up after 90Sr/90Y beta-irradiation for the treatment of coronary in-stent restenosis.

    Science.gov (United States)

    Schiele, Thomas M; Herbst, Jan; Pöllinger, Barbara; Rieber, Johannes; König, Andreas; Sohn, Hae-Young; Krötz, Florian; Leibig, Marcus; Belka, Claus; Klauss, Volker

    2011-03-01

    Since late vessel failure has been speculated as a significant limitation of vascular brachytherapy (VBT), we conducted a prospective clinical evaluation at 6, 12, 24, 36 and 60 months follow-up after irradiation with (90)Sr/(90)Y for in-stent restenosis (ISR) regardless of the patient's symptomatic status. Complete five-year follow-up is reported for 104 consecutive patients. The cumulative rate of death was 13.5% (6 months: 0.96%; 12 months: 2.88%; 24 months: 4.81%; 36 months: 7.69%), of acute myocardial infarction 4.81% (2.88%; 4.81%; 4.81%; 4.81%), of late thrombotic occlusion 4.81% (3.85%; 4.81%; 4.81%; 4.81%), of target lesion revascularization (TLR) 27.9% (8.65%; 12.5%; 17.3%; 21.2%), of target vessel revascularization (TVR) 43.3% (12.5%; 19.2%; 22.1%; 29.8%), and of all major adverse cardiovascular events (MACE) 61.5% (16.3%; 26.9%; 31.7%; 42.3%), respectively. Considered that the annual incidence of TVR after the first year following drug-eluting stenting for in-stent restenosis has been reported as approximately 3% per year, an incidence of 5.8% per year following VBT of our study population clearly indicates a more pronounced, delayed and, even in the fifth year after the index procedure, ongoing restenotic process following beta-irradiation of in-stent restenotic lesions associated with clinically relevant adverse cardiovascular events.

  16. The use of gel dosimetry to measure the 3D dose distribution of a {sup 90}Sr/{sup 90}Y intravascular brachytherapy seed

    Energy Technology Data Exchange (ETDEWEB)

    Massillon-JL, G; Minniti, R; Mitch, M G; Soares, C G [Ionizing Radiation Division, National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Maryanski, M J [MGS Research, Inc., Madison, CT 06443 (United States)], E-mail: massillon@fisica.unam.mx

    2009-03-21

    Absorbed dose distributions in 3D imparted by a single {sup 90}Sr/{sup 90}Y beta particle seed source of the type used for intravascular brachytherapy were investigated. A polymer gel dosimetry medium was used as a dosemeter and phantom, while a special high-resolution laser CT scanner with a spatial resolution of 100 {mu}m in all dimensions was used to quantify the data. We have measured the radial dose function, g{sub L}(r), observing that g{sub L}(r) increases to a maximum value and then decreases as the distance from the seed increases. This is in good agreement with previous data obtained with radiochromic film and thermoluminescent dosemeters (TLDs), even if the TLDs underestimate the dose at distances very close to the seed. Contrary to the measurements, g{sub L}(r) calculated through Monte Carlo simulations and reported previously steadily decreases without a local maximum as a function of the distance from the seed. At distances less than 1.5 mm, differences of more than 20% are observed between the measurements and the Monte Carlo calculations. This difference could be due to a possible underestimation of the energy absorbed into the seed core and encapsulation in the Monte Carlo simulation, as a consequence of the unknown precise chemical composition of the core and its respective density for this seed. The results suggest that g{sub L}(r) can be measured very close to the seed with a relative uncertainty of about 1% to 2%. The dose distribution is isotropic only at distances greater than or equal to 2 mm from the seed and is almost symmetric, independent of the depth. This study indicates that polymer gel coupled with the special small format laser CT scanner are valid and accurate methods for measuring the dose distribution at distances close to an intravascular brachytherapy seed.

  17. Comparison of ⁹⁰Y and ¹⁷⁷Lu measurement capability in UK and European hospitals.

    Science.gov (United States)

    Fenwick, Andrew; Baker, Michaela; Ferreira, Kelley; Keightley, John

    2014-05-01

    Comparison exercises involving (90)Y and (177)Lu were performed during 2009 and 2012, respectively, to assess the measurement capability of hospitals in the UK and Europe. The results from the measurement of a typical liquid solution of (90)Y show that only 40% of participants could measure the solution to within 5% of the certificated value and that a significant -6% bias was present due to the use of non-standard geometries for the calibration of equipment. The results from the measurement of a standard liquid solution of (177)Lu show that 81% of participants could measure to within 5% of the certificated value and in fact 65% of these results were within 2% of the certificated value, showing administered activities can be far more accurately measured for (177)Lu than for (90)Y and that (177)Lu has a far smaller geometry dependence. These studies were performed to identify specific measurement issues in the user community and to identify areas where future research should be focused. In addition to this the work allows the participants to adjust measurement practice and identify key measurement issues.

  18. Synthesis and characterization of a novel acryl amide-based yttrium imprinted sorbent via the ATRP approach for the preparation of medical-grade {sup 90}Y

    Energy Technology Data Exchange (ETDEWEB)

    Abedi, Mahvash [Nuclear Schience and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Shahid Beheshti Univ., Tehran (Iran, Islamic Republic of). Dept. of Chemistry; Shirvani-Arani, Simindokht; Bahrami-Samani, Ali [Nuclear Schience and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Nabid, Mohammad Reza [Shahid Beheshti Univ., Tehran (Iran, Islamic Republic of). Dept. of Chemistry

    2016-05-01

    Because of its favorable radionuclidic properties (pure beta emitter, E{sub βmax} = 2.28 MeV, T{sub 1/2} = 64.1 h), the preparation of carrier free {sup 90}Y is of a great importance in radiopharmacy. Herein, we report the synthesis, characterization, and application of a novel yttrium sorbent prepared on the basis of the ion-imprinting concept. The ion-imprinted polymer (IIP) was prepared by atom transfer radical copolymerization of acryl amide (AAm, functional monomer) and N,N'-methylenebisacrylamide (MBAAm) crosslinking agent in the presence of a complex of yttrium ions (template ions) with a homemade chelator, i.e., 2,2-bis(2-bromo-2-methylpropanoate)propane-1,3-disuccinate (also as initiator). For elimination of yttrium ions, which act as the template, the prepared particles were treated with 50% v:v HCl: H{sub 2}O to produce yttrium-imprinted polymeric sorbent. To control the imprinting effect, corresponding non-imprinted particles (NIP) were prepared in a similar manner except that yttrium ions were not used. The synthesized chemicals for the preparation of the chelator-initiator compound and the product itself were assessed in every step using {sup 1}H-NMR analysis. NIP and YIP were subjected to X-ray diffraction (XRD), infra-red spectroscopy (IR) and BET surface area analysis for characterization studies. Sorption/desorption studies were conducted, and the effects of potentially interfering ions, such as Sr{sup 2+} (α = 119.69) and Zr{sup 4+} (α = 73.01) in presence of radio-yttrium, were investigated (particle size: 50-100 μm, resultant recovery of > 99% within 60 min and a capacity of 33.33 mg Y(III) per gram of sorbent). The results showed that amounts of radio-yttrium as low as 250 μg could be extracted effectively with high radionuclidic and radiochemical purity from macro-gram amounts of strontium.

  19. Boosted selective internal radiation therapy with {sup 90}Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept

    Energy Technology Data Exchange (ETDEWEB)

    Garin, E.; Lenoir, L. [Comprehensive Cancer Center, Institute Eugene Marquis, Department of Nuclear Medicine, CS 44229, Rennes (France); University of Rennes 1, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Edeline, J. [University of Rennes 1, Rennes (France); Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France); Laffont, S. [Comprehensive Cancer Center, Institute Eugene Marquis, Department of Nuclear Medicine, CS 44229, Rennes (France); Mesbah, H.; Poree, P. [Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Informatics, CS 44229, Rennes (France); Sulpice, L. [INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Centre Hospitalier Universitaire Pontchaillou, Department of Digestive Surgery, Rennes (France); Boudjema, K. [University of Rennes 1, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Centre Hospitalier Universitaire Pontchaillou, Department of Digestive Surgery, Rennes (France); Mesbah, M. [University of Pierre et Marie Curie, Paris (France); Guillygomarc' h, A. [Centre Hospitalier Universitaire Pontchaillou, Department of Hepatology, Rennes (France); Quehen, E. [Centre Hospitalier Universitaire Pontchaillou, Department of Radiology, Rennes (France); Pracht, M. [Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France); Raoul, J.L. [Comprehensive Cancer Center, Institute Paoli Calmette, Department of Medical Oncology, Marseille (France); Clement, B. [INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Rolland, Y. [Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Imaging, CS 44229, Rennes (France); Boucher, E. [INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France)

    2013-07-15

    To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with {sup 90}Y-loaded glass microspheres (TheraSphere registered). TheraSphere registered was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS). The response rate was 78.8 %. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p < 0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100 % and overall accuracy of 90 %. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4 %), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2-9.5 months) and 11.5 months (2-31 months), respectively, in patients with TD <205 Gy and 13 months (10-16 months) and 23.2 months (17.5-28.5 months), respectively, in those with TD >205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD <205 Gy and 10 months (6-15.2 months) and 21.5 months (12-28.5 months), respectively, in those with TD >205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83 % and overall accuracy of 97 %. Dosimetry based on MAA SPECT/CT was

  20. Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours

    Energy Technology Data Exchange (ETDEWEB)

    Essen, Martijn van; Krenning, Eric P.; Jong, Marion De; Valkema, Roelf; Kwekkeboom, Dik J. [Dept. of Nuclear Medicine, Erasmus MC, ' s Gravendijkwal 230, Rotterdam (Netherlands)

    2007-08-15

    Peptide Receptor Radionuclide Therapy (PRRT) with radiolabelled somatostatin analogues is a promising treatment option for patients with inoperable or metastasised neuroendocrine tumours. Symptomatic improvement may occur with all of the various {sup 111}In, {sup 90}Y, or {sup 177}Lu-labelled somatostatin analogues that have been used. Since tumour size reduction was seldom achieved with {sup 111}Indium labelled somatostatin analogues, radiolabelled somatostatin analogues with beta-emitting isotopes like {sup 90}Y and {sup 177}Lu were developed. Reported anti-tumour effects of [{sup 90}Y-DOTA0,Tyr3]octreotide vary considerably between various studies: Tumour regression of 50% or more was achieved in 9 to 33% (mean 22%). With [{sup 177}Lu-DOTA0,Tyr3]octreotate treatments, tumour regression of 50% or more was achieved in 28% of patients and tumour regression of 25 to 50% in 19% of patients, stable disease was demonstrated in 35% and progressive disease in 18%. Predictive factors for tumour remission were high tumour uptake on somatostatin receptor scintigraphy and limited amount of liver metastases. The side-effects of PRRT are few and mostly mild, certainly when using renal protective agents: Serious side-effects like myelodysplastic syndrome or renal failure are rare. The median duration of the therapy response for [{sup 90}Y-DOTA0,Tyr3]octreotide and [{sup 177}Lu-DOTA0,Tyr3]octreotate is 30 months and more than 36 months respectively. Lastly, quality of life improves significantly after treatment with [{sup 177}Lu-DOTA0,Tyr3]octreotate. These data compare favourably with the limited number of alternative treatment approaches, like chemotherapy. If more widespread use of PRRT is possible, such therapy might become the therapy of first choice in patients with metastasised or inoperable gastroenteropancreatic neuroendocrine tumours. Also the role in somatostatin receptor expressing non-GEP tumours, like metastasised paraganglioma/pheochromocytoma and non

  1. Combination of chemical separation and data treatment for {sup 55}Fe, {sup 63}Ni, {sup 99}Tc, {sup 137}Cs and {sup 90}Sr/{sup 90}Y activity determination in radioactive waste by liquid scintillation

    Energy Technology Data Exchange (ETDEWEB)

    Mellado, J. [Departament de Quimica Analitica, Facultat de Quimica, Universitat de Barcelona, C/Marti Franques 1, 08028 Barcelona (Spain); Tarancon, A. [Departament de Quimica Analitica, Facultat de Quimica, Universitat de Barcelona, C/Marti Franques 1, 08028 Barcelona (Spain); Garcia, J.F. [Departament de Pintura, Facultat de Belles Arts, Universitat de Barcelona, C/Pau Gargallo 4, 08028 Barcelona (Spain)]. E-mail: jfgarcia@apolo.qui.ub.es; Rauret, G. [Departament de Quimica Analitica, Facultat de Quimica, Universitat de Barcelona, C/Marti Franques 1, 08028 Barcelona (Spain); Warwick, P. [Geoscience Advisory Unit, Southampton Oceanography Centre, Southampton SO14 3ZH (United Kingdom)

    2005-08-01

    Routine operations involving nuclear reactors and decommissioning activities require numerous chemical analyses. Most of the procedures developed for these chemical characterisations involve several separation steps to prepare the sample for measurement. Chemical treatments are time- and manpower-consuming, labour intensive and produce significant quantities of waste. In order to address this problem, we evaluate a data treatment procedure (multivariate calibration-PLS), which we propose as a substitute to some of these separation steps. Mixtures of beta emitter radionuclides of increasing complexity ({sup 90}Sr/{sup 90}Y-{sup 99}Tc, {sup 90}Sr/{sup 90}Y-{sup 99}Tc-{sup 63}Ni-{sup 137}Cs and {sup 90}Sr/{sup 90}Y-{sup 99}Tc-{sup 63}Ni-{sup 137}Cs-{sup 55}Fe) have been measured by liquid scintillation (LS) counting. The influences of quenching and level of activity was evaluated and the activity of unknown samples determined. Despite the spectra overlapping and low resolution of LS, relative errors in the activities quantification of unknown samples inside the range covered by the calibration matrix are lower than 15% whatever the number of radionuclides included in the solution was.

  2. Procedure to carry out leakage test in beta radiation sealed sources emitters of {sup 90}Sr/{sup 90}Y; Procedimiento para realizar prueba de fuga en fuentes selladas de radiacion beta emisoras de {sup 90}Sr/{sup 90}Y

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, J. T., E-mail: trinidad.alvarez@inin.gob.m [ININ, Departamento de Metrologia de Radiaciones Ionizantes, Laboratorio Secundario de Calibracion Dosimetrica, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2010-09-15

    In the alpha-beta room of the Secondary Laboratory of Dosimetric Calibration of the Metrology Department of Ionizing Radiations ophthalmic applicators are calibrated in absorbed dose terms in water D{sub w}; these applicators, basically are emitter sealed sources of pure beta radiation of {sup 90}Sr / {sup 90}Y. Concretely, the laboratory quality system indicates to use the established procedure for the calibration of these sources, which establishes the requirement of to carry out a leakage test, before to calibrate the source. However, in the Laboratory leakage test certificates sent by specialized companies in radiological protection services have been received, in which are used gamma spectrometry equipment s for beta radiation leakage tests, since it is not reliable to detect pure beta radiation with a scintillating detector with NaI crystal, (because it could detect the braking radiation produced in the detector). Therefore the Laboratory has had to verify the results of the tests with a correct technique, with the purpose of determining the presence of sources with their altered integrity and radioactive material leakage. The objective of this work is to describe a technique for beta activity measurement - of the standard ISO 7503, part 1 (1988) - and its application with a detector Gm plane (type pankage) in the realization of leakage tests in emitter sources of pure beta radiation, inside the mark of quality assurance indicated by the report ICRU 76. (Author)

  3. Partition Model-Based 99mTc-MAA SPECT/CT Predictive Dosimetry Compared with 90Y TOF PET/CT Posttreatment Dosimetry in Radioembolization of Hepatocellular Carcinoma: A Quantitative Agreement Comparison.

    Science.gov (United States)

    Gnesin, Silvano; Canetti, Laurent; Adib, Salim; Cherbuin, Nicolas; Silva Monteiro, Marina; Bize, Pierre; Denys, Alban; Prior, John O; Baechler, Sebastien; Boubaker, Ariane

    2016-11-01

    (90)Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment (99m)Tc-macroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of (99m)Tc-MAA SPECT/CT and posttreatment dosimetry based on (90)Y time-of-flight (TOF) PET/CT. We compared the (99m)Tc-MAA SPECT/CT results for 27 treatment sessions (25 HCC patients, 41 tumors) with (90)Y SIRT (7 glass spheres, 20 resin spheres) and the posttreatment (90)Y TOF PET/CT results. Three-dimensional voxelized dose maps were computed from the (99m)Tc-MAA SPECT/CT and (90)Y TOF PET/CT data. Mean absorbed dose ([Formula: see text]) was evaluated to compute the predicted-to-actual dose ratio ([Formula: see text]) in tumor volumes (TVs) and nontumor volumes (NTVs) for glass and resin spheres. The Lin concordance ([Formula: see text]) was used to measure accuracy ([Formula: see text]) and precision (ρ). Administered activity ranged from 0.8 to 1.9 GBq for glass spheres and from 0.6 to 3.4 GBq for resin spheres, and the respective TVs ranged from 2 to 125 mL and from 6 to 1,828 mL. The mean dose [Formula: see text] was 240 Gy for glass and 122 Gy for resin in TVs and 72 Gy for glass and 47 Gy for resin in NTVs. [Formula: see text] was 1.46 ± 0.58 (0.65-2.53) for glass and 1.16 ± 0.41 (0.54-2.54) for resin, and the respective values for [Formula: see text] were 0.88 ± 0.15 (0.56-1.00) and 0.86 ± 0.2 (0.58-1.35). DR variability was substantially lower in NTVs than in TVs. The Lin concordance between [Formula: see text] and [Formula: see text] (resin) was significantly better for tumors larger than 150 mL than for tumors 150 mL or smaller ([Formula: see text] = 0.93 and [Formula: see text] = 0.95 vs. [Formula: see text] = 0.57 and [Formula: see text] = 0.93; P < 0.05). In (90)Y

  4. Computed tomography hepatic arteriography has a hepatic falciform artery detection rate that is much higher than that of digital subtraction angiography and 99mTc-MAA SPECT/CT: Implications for planning 90Y radioembolization?

    Energy Technology Data Exchange (ETDEWEB)

    Burgmans, M.C., E-mail: mburgmans@hotmail.com [Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore 169608 (Singapore); Too, C.W., E-mail: too.chow.wei@singhealth.com.sg [Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore 169608 (Singapore); Kao, Y.H., E-mail: yung.h.kao@gmail.com [Department of Nuclear Medicine and PET, Singapore General Hospital, Outram Road, Singapore 169608 (Singapore); Goh, A.S.W., E-mail: anthony.goh.s.w@sgh.com.sg [Department of Nuclear Medicine and PET, Singapore General Hospital, Outram Road, Singapore 169608 (Singapore); Chow, P.K.H., E-mail: gsupc@singnet.com.sg [Department of General Surgery, Singapore General Hospital, Outram Road, Singapore 169608 (Singapore); Office of Clinical Sciences, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857 (Singapore); Department of Surgical Oncology, National Cancer Center Singapore, 11 Hospital Drive, Singapore 169610 (Singapore); Tan, B.S., E-mail: tan.bien.soo@sgh.com.sg [Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore 169608 (Singapore); Tay, K.H., E-mail: tay.kiang.hiong@sgh.com.sg [Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore 169608 (Singapore); Lo, R.H.G., E-mail: richard.lo.h.g@sgh.com.sg [Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore 169608 (Singapore)

    2012-12-15

    Purpose: To compare the hepatic falciform artery (HFA) detection rates of digital subtraction angiography (DSA), computed tomography hepatic arteriography (CTHA) and 99mTc-macroaggregated albumin (99mTc-MAA) single photon emission computed tomography with integrated CT (SPECT/CT) and to correlate HFA patency with complication rates of yttrium-90 (90Y) radioembolization. Material and methods: From August 2008 to November 2010, 79 patients (range 23–83 years, mean 62.3 years; 67 male) underwent pre-treatment DSA, CTHA and 99mTc-MAA scintigraphy (planar/SPECT/CT) to assess suitability for radioembolization with 90Y resin microspheres. Thirty-seven patients were excluded from the study, because CTHA was performed with a catheter position that did not result in opacification of the liver parenchyma adjacent to the falciform ligament. DSA, CTHA and 99mTc-MAA SPECT/CT images and medical records were retrospectively reviewed. Results: A patent HFA was detected in 22 of 42 patients (52.3%). The HFA detection rates of DSA, CTHA and 99mTc-MAA SPECT/CT were 11.9%, 52.3% and 13.3%, respectively (p < 0.0001). An origin from the segment 4 artery was seen in 51.7% of HFAs. Prophylactic HFA coil-embolization prior to 90Y microspheres infusion was performed in 2 patients. Of the patients who underwent radioembolization with a patent HFA, none developed supra-umbilical radiation dermatitis. One patient experienced epigastric pain attributed to post-embolization syndrome and was managed conservatively. Conclusion: The HFA detection rate of CTHA is superior to that of DSA and 99mTc-MAA SPECT/CT. Complications related to non-target radiation of the HFA vascular territory rarely occur, even in patients undergoing radioembolization with a patent HFA.

  5. Tumour targeting and radiation dose of radioimmunotherapy with {sup 90}Y-rituximab in CD20+ B-cell lymphoma as predicted by {sup 89}Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Muylle, Kristoff [Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium); Universite Libre de Bruxelles, Department of Nuclear Medicine, Jules Bordet Institute, Brussels (Belgium); Flamen, Patrick; Guiot, Thomas; Ghanem, Ghanem; Meuleman, Nathalie; Bourgeois, Pierre; Vanderlinden, Bruno; Vaes, Melanie; Bron, Dominique [Universite Libre de Bruxelles, Jules Bordet Institute, Brussels (Belgium); Vugts, Danielle J.; Dongen, Guus A.M.S. van [VU University Medical Centre, Amsterdam (Netherlands); Everaert, Hendrik [Vrije Universiteit Brussel, UZ Brussel, Brussels (Belgium); Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium)

    2015-07-15

    To compare using immuno-PET/CT the distribution of {sup 89}Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with {sup 90}Y-labelled rituximab in CD20+ B-cell lymphoma. Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline {sup 89}Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m{sup 2}) of unlabelled rituximab followed by injection of {sup 89}Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by {sup 90}Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. With a cold rituximab preload, the calculated whole-body dose of {sup 90}Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the ''prerituximab era''. (orig.)

  6. Development of radiopharmaceutical for radiosinovectomy; Desenvolvimento de radiofarmaco para radiosinovectomia

    Energy Technology Data Exchange (ETDEWEB)

    Couto, Renata Martinussi

    2009-07-01

    Radiopharmaceuticals prepared with different radionuclides have been used in diagnostic and therapeutic procedures in Nuclear Medicine. The interest in radionuclidic therapy has been increased in last years, with the introduction of new radiopharmaceuticals applied in the destruction of specific cells or to prevent its undesired proliferation. Radiosinovectomy (RSV) is a therapeutic modality that uses radiopharmaceuticals administered in the intra-articular cavity and represents an alternative to the treatment of different arthropaties and, in particular, the arthropaties derived from rheumatoid arthritis and haemophilic. The objective of the present work was to study the labeling of compounds with {sup 90}Y and {sup 177}Lu in order to improve the production conditions and quality control procedures, study the stability of the labeled compounds and preliminary biodistribution studies of the radiopharmaceuticals with potential for RSV applications. The study of the production of {sup 90}Y citrate colloid ({sup 90}Y-Cit) was based in a labeling procedure using {sup 90}Y Cl{sub 3} solution (37 - 54 MBq) that was previously dried, followed by the addition of yttrium nitrate and sodium citrate in p H 7 at 37 deg C for 30 minutes. The production of hydroxyapatite (HA) labeled with {sup 90}Y was based in a labeling procedure using mono hydrated citric acid, yttrium nitrate and {sup 90}Y Cl{sub 3} solution (37 - 370 MBq). The reaction mixture was incubated for 30 minutes at room temperature and the HA was introduced in aqueous medium and the reaction proceed for 30 minutes under strong stirring. {sup 177}Lu-HA was produced using {sup 177}Lu Cl{sub 3} solution (296 MBq), in presence of lutetium oxide in NaCl medium, p H 7, under continuous stirring for 30 minutes at room temperature. Several reaction parameters were studied for the three radiopharmaceuticals. Labeling yield was determined after particles were centrifuged and washed with NaCl 0,9%. Radiochemical purity was

  7. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this t...

  8. Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with {sup 177}Lu-D OTATATE

    Energy Technology Data Exchange (ETDEWEB)

    Sansovini, Maddalena; Severi, Stefano; Ianniello, Annarita; Nicolini, Silvia; Fantini, Lorenzo; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine Unit, Meldola (Italy); Mezzenga, Emilio [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Ferroni, Fabio [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Radiology Unit, Meldola (Italy); Scarpi, Emanuela; Monti, Manuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Bongiovanni, Alberto [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Cingarlini, Sara [University of Verona, Department of Oncology, Verona Comprehensive Cancer Network, G.B. Rossi Hospital, Verona (Italy); Grana, Chiara Maria; Bodei, Lisa [European Institute of Oncology Milan (IEO), Division of Nuclear Medicine, Milan (Italy)

    2017-03-15

    Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs. From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6-8 weeks), according to kidney and bone marrow parameters. Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P < 0.0002), regardless of the total activity administered. Both FA and RA are active in patients undergoing Lu-PRRT. However, an FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our results indicate that FDG PET is an independent prognostic factor in this patient setting. (orig.)

  9. 68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies

    National Research Council Canada - National Science Library

    Weineisen, Martina; Schottelius, Margret; Simecek, Jakub; Baum, Richard P; Yildiz, Akin; Beykan, Seval; Kulkarni, Harshad R; Lassmann, Michael; Klette, Ingo; Eiber, Matthias; Schwaiger, Markus; Wester, Hans-Jürgen

    2015-01-01

    ...) in metastatic prostate cancer (PC), the goal of this study was the development, preclinical evaluation, and first proof-of-concept investigation of a PSMA inhibitor for imaging and therapy (PSMA I&T) for (68)Ga-based PET and (177...

  10. (99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine-concentrating dedifferentiated thyroid carcinoma metastases: an unusual alternative diagnosis.

    Science.gov (United States)

    Basu, Sandip; Joshi, Amit

    2014-07-01

    The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic-predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine ablation) is illustrated. The whole-body radioiodine scan and battery of serum tumor markers were normal. Multiple metastatic foci in the liver and skeleton were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a highly positive scan in the setting of apparent non-iodine-concentrating metastatic disease in a patient of differentiated thyroid carcinoma.

  11. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2015-09-01

    Sincerely , Rosemary Kraemer, Ph.D. Director, Human Research Protections Program Please note the following important information about this approval...sciences journal literature , and be made publicly available within twelve months of publication. The Library and RASP have prepared general information

  12. Dynamic and static small-animal SPECT in rats for monitoring renal function after 177Lu-labeled Tyr3-octreotate radionuclide therapy.

    NARCIS (Netherlands)

    Melis, M.; Swart, J.; Visser, M. de; Berndsen, S.C.; Koelewijn, S.; Valkema, R.; Boerman, O.C.; Krenning, E.P.; Jong, M. de

    2010-01-01

    High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with beta-particle-emitting radiolabeled somatostatin analogs will lead to renal failure several months after treatment, urging the coinfusion of the cationic amino acids lysine and arginine to reduce the renal

  13. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Biochemically Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2010-09-01

    review on hold pending additional funding - University of Medicine and Dentistry , New Jersey – scientific review - Nevada Cancer Institute – scientific...BIOCHEMICALLY RELAPSED PROSTATE CANCER AFTER LOCAL THERAPY Scott T. Tagawa, Joseph Osborne, Paul J. Christos, Shankar Vallabhajosula, Kristen Petrillo

  14. Intrahepatic arterial {sup 99M}Technetium ({sup 99M}Tc) macroaggregated albumin (MAA) scan prior to selective internal radiation therapy (SIRT) with {sup 90}Yttrium (90Y) microspheres for liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Langan, P.; Alwan, M.H.; Stubbs, R.S. [Wakefield Hospital, Wellington (New Zealand). Department of Radiology and Gastroenterology

    1998-06-01

    Full text: {sup 90}Y-microspheres is a regional treatment modality that is used for patients with inoperable primary or secondary liver tumours. Success of treatment depends on the increased uptake and retention of the {sup 90}Y by the tumour relative to normal liver, and the absence of significant extrahepatic shunting. Between February and November 1997, 32 patients were treated with SIRT at Wakefield Gastroenterology Centre. A group of these patients received subsequent hepatic arterial infusion chemotherapy (HAI) using 5-Fluorouracil (5FU). {sup 99m}Tc-MAA in a median dose of 135 MBq (3.6 mCi) [range: 120-150 MBq, or 3.4- 4.1 mCi] with >90% of the particles 10 to 90 {mu}m in size and none greater than 150 {mu}n was injected through a subcutaneously implanted port inserted at laparotomy in the gastroduodenal artery which led to the common hepatic artery (26 patients), or through a transfemoral catheter positioned in the hepatic artery (6 patients). Scintigraphic images of the liver, lungs and gastroduodenal regions were taken with a GE Statcam 4000i gamma camera. The total count rate was computed from the digitised image, and the percentages of activity were calculated as the ratio of lung counts-to-total counts. A liver/lung shunt of < 15% was a prerequisite for treatment with SIRT. There were 18 males and 14 females with a median age of 60.5 years (range: 29 to 76). Twenty eight patients had secondary tumours (23 colorectal, 5 others) and 4 patients had hepatocellular cardnoma (HCC). The median liver/lung shunt was 0.6% (range: 0% to 9.3%). The median shunt for HCC was 0.7% (range: 0% to 2%) and for the secondary tumours 0.6% (<0.1% to 9.3%). No significant shunt was detected in the gastroduodenal region. Assessment of lung shunting of {sup 99m}Tc-MAA scan is useful for excluding patients who may be at risk of pulmonary irradiation, or significant systemic toxicity after regional chemotherapy

  15. Semi-quantitative analysis of post-transarterial radioembolization {sup 90}Y Microsphere position emission tomography combined with computed tomography (PET/CT) images in advance liver malignancy: Comparison with {sup 99m}Tc macroaggregated albumin (MAA) single photon emission computed tomography (SPECT)

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, Seung Hong; Kim, Sung Eun; Cho, Jae Hyuk; Park, Ju Kyung; Kim, Yun Hwan; Choe, Jae Gol [Korea University Anam Hospital, Seoul (Korea, Republic of); Eo, Jae Seon; Park, So Yeon; Lee, Eun Sub [Dept. of Nuclear Medicine, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2016-03-15

    The purpose of this study is to evaluate the correlation between pretreatment planning technetium-99m ({sup 99}mTc) macroaggregated albumin (MAA) SPECT images and posttreatment transarterial radioembolization (TARE) yttirum-90 ({sup 90}Y) PET/CT images by comparing the ratios of tumor-to-normal liver counts. Fifty-two patients with advanced hepatic malignancy who underwent {sup 90}Y microsphere radioembolization from January 2010 to December 2012 were retrospectively reviewed. Patients had undergone {sup 99}mTc MAA intraarterial injection SPECT for a pretreatment evaluation of microsphere distribution and therapy planning. After the administration of {sup 90}Y microspheres, the patients underwent posttreatment {sup 90}Y PET/CT within 24 h. For semiquantitative analysis, the tumor-to-normal uptake ratios in {sup 90}Y PET/CT (TNR-yp) and {sup 99}mTc MAA SPECT (TNR-ms) as well as the tumor volumes measured in angiographic CT were obtained and analyzed. The relationship of TNR-yp and TNR-ms was evaluated by Spearman's rank correlation and Wilcoxon's matched pairs test. In a total of 79 lesions of 52 patients, the distribution of microspheres was well demonstrated in both the SPECT and PET/CT images. A good correlation was observed of between TNR-ms and TNR-yp (rho value = 0.648, p < 0.001). The TNR-yp (median 2.78, interquartile range 2.43) tend to show significantly higher values than TNR-ms (median 2.49, interquartile range of 1.55) (p = 0.012). The TNR-yp showed weak correlation with tumor volume (rho = 0.230, p = 0.041). The 99mTc MAA SPECT showed a good correlation with {sup 90}Y PET/CT in TNR values, suggesting that {sup 99}mTc MAA can be used as an adequate pretreatment evaluation method. However, the {sup 99}mTc MAA SPECT image consistently shows lower TNR values compared to 90Y PET/CT, which means the possibility of underestimation of tumorous uptake in the partition dosimetry model using {sup 99}mTc MAA SPECT. Considering that

  16. Short-course R-CHOP followed by 90Y-Ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients: 7-year long-term results

    Science.gov (United States)

    Stefoni, V; Casadei, B; Bottelli, C; Gaidano, G; Ciochetto, C; Cabras, M G; Ansuinelli, M; Argnani, L; Broccoli, A; Gandolfi, L; Pellegrini, C; Zinzani, P L

    2016-01-01

    An update at 7 years was conceived for our multicenter phase II study in which 55 elderly high-risk untreated diffuse large B-cell lymphoma patients were treated with 90Y-ibritumomab tiuxetan after a short course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) as long-term follow-up analyses of this combined therapeutic modality are lacking. The overall response rate to the entire regimen was 80%, including 73% (40/55) of complete response (CR) rate and 7% (4/55) of partial response rate. At the time of writing, 24/55 (43.6%) patients experienced a progression disease and 20 of 40 (50%) patients who obtained a CR are still alive in continuous CR. With a median follow-up of 7 years, the disease-free survival was 43.3% and the progression-free survival was 36.1%. The overall survival at 7.9 years was 38.9% (27 deaths mainly because of lymphoma). Two patients developed secondary hematological malignancies, an acute myeloid leukemia and a myelodysplastic syndrome, at 4 and 3 years from radioimmunotherapy, respectively. Our data confirm the feasibility, efficacy and safety of four cycles of R-CHOP followed by radioimmunotherapy consolidation even in the long term: this combination allows dispensing less chemotherapy in a frail group of patients without invalidating response quality and duration. PMID:27176801

  17. Accounting for beta-particle energy loss to cortical bone via paired-image radiation transport (PIRT).

    Science.gov (United States)

    Shah, Amish P; Rajon, Didier A; Patton, Phillip W; Jokisch, Derek W; Bolch, Wesley E

    2005-05-01

    approximately 14% to 76% for high-energy beta emitters (32p, 188Re, and 90Y). The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high energy beta emitters.

  18. National pattern for the realization of the unit of the dose speed absorbed in air for beta radiation. (Method: Ionometer, cavity of Bragg-Gray implemented in an extrapolation chamber with electrodes of variable separation, exposed to a field of beta radiation of {sup 90}Sr/{sup 90}Y); Patron Nacional para la realizacion de la unidad de la rapidez de dosis absorbida en aire para radiacion beta. (Metodo: Ionometrico, cavidad de Bragg-Gray implementada en una camara de extrapolacion con electrodos de separacion variable, expuesta a un campo de radiacion beta de {sup 90}Sr/{sup 90}Y)

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, M. T.; Morales P, J. R. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2001-01-15

    From the year of 1987 the Department of Metrology of the ININ, in their Secondary Laboratory of Calibration Dosimetric, has a patron group of sources of radiation beta and an extrapolation chamber of electrodes of variable separation.Their objective is to carry out of the unit of the dose speed absorbed in air for radiation beta. It uses the ionometric method, cavity Bragg-Gray in the extrapolation chamber with which it counts. The services that offers are: i) it Calibration : Radioactive Fuentes of radiation beta, isotopes: {sup 90}Sr/{sup 90}Y; Ophthalmic applicators {sup 9}0{sup S}r/{sup 90}Y; Instruments for detection of beta radiation with to the radiological protection: Ionization chambers, Geiger-Muller, etc.; Personal Dosemeters. ii) Irradiation with beta radiation of materials to the investigation. (Author)

  19. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Kidd, Mark; Drozdov, Ignat; Lepensky, Christopher; Modlin, Irvin M. [Yale School of Medicine, Department of Surgery, New Haven, CT (United States); Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Cremonesi, Marta [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Kwekkeboom, Dik J.; Krenning, Eric P. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Baum, Richard P. [Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotheraphy and Molecular Imaging, Bad Berka (Germany)

    2015-01-15

    Peptide receptor radionuclide therapy (PRRT) with {sup 90}Y and {sup 177}Lu provides objective responses in neuroendocrine tumours, and is well tolerated with moderate toxicity. We aimed to identify clinical parameters predictive of long-term renal and haematological toxicity (myelodysplastic syndrome and acute leukaemia). Of 807 patients studied at IEO-Milan (1997-2013), 793 (98 %) received {sup 177}Lu (278, 34.4 %), {sup 90}Y (358, 44.4 %) or {sup 177}Lu and {sup 90}Y combined (157. 19.5 %), and 14 (2 %) received combinations of PRRT and other agents. Follow-up was 30 months (1-180 months). The parameters evaluated included renal risk factors, bone marrow toxicity and PRRT features. Data analysis included multiple regression, random forest feature selection, and recursive partitioning and regression trees. Treatment with {sup 90}Y and {sup 90}Y + {sup 177}Lu was more likely to result in nephrotoxicity than treatment with {sup 177}Lu alone (33.6 %, 25.5 % and 13.4 % of patients, respectively; p < 0.0001). Nephrotoxicity (any grade), transient and persistent, occurred in 279 patients (34.6 %) and was severe (grade 3 + 4) in 12 (1.5 %). In only 20-27 % of any nephrotoxicity was the disease modelled by risk factors and codependent associations (p < 0.0001). Hypertension and haemoglobin toxicity were the most relevant factors. Persistent toxicity occurred in 197 patients (24.3 %). In only 22-34 % of affected patients was the disease modelled by the clinical data (p < 0.0001). Hypertension (regression coefficient 0.14, p < 0.0001) and haemoglobin toxicity (regression coefficient 0.21, p < 0.0001) were pertinent factors. Persistent toxicity was associated with shorter PRRT duration from the first to the last cycle (mean 387 vs. 658 days, p < 0.004). Myelodysplastic syndrome occurred in 2.35 % of patients (modelled by the clinical data in 30 %, p < 0.0001). Platelet toxicity grade (2.05 ± 1.2 vs. 0.58 ± 0.8, p < 0.0001) and longer PRRT duration (22.6 ± 24 vs. 15.5

  20. Synthesis and application of a novel cysteine-based DTPA-NCS for targeted radioimmunotherapy.

    Science.gov (United States)

    Lee, So-Young; Hong, Young Don; Kim, Hak-Sung; Choi, Sun-Ju

    2013-04-01

    For the development of safe and effective protein-based radiolabeled complexes such as radioimmunotherapy (RIT), the selection of the radionuclides and the chelating agents used for the radiolabeling of tumor-targeting molecules is a critical factor. We aim to synthesize a novel bifunctional chelating agent containing the isothiocyanate group for easy conjugation with antibodies having the characteristics of high stable chelation with therapeutic radionuclides. We have synthesized the DTPA analogue retaining L-cysteine as a core ligand of the thiol group. The chelating power of cysteine-based DTPA-NCS (cys-DTPA-NCS) was compared with that of commercial ρ-SCN-Bn-DTPA. In an application, the cetuximab was radioimmunoconjugated with (177)Lu using cys-DTPA-NCS. The affinity was tested in a cell line overexpressing EGFR. A therapy study was conducted in nude mice with subcutaneous HT-29 xenografts. The cys-DTPA-NCS presents an excellent ability to chelate as compared to the ρ-SCN-Bn-DTPA. For mean ratio chemical labeling yields of 95%, the result was 0.97. (177)Lu-cys-DTPA-NCS-cetuximab was prepared under ambient condition with a high radiolabeling yield and the radiochemical purity was sustained for at least 6days. The IC50 value of the (177)Lu-labeled cetuximab was 10nM (95% confidence). The stability and therapeutic efficacy of the candidate radiopharmaceutical were verified. The new DTPA derivative, cys-DTPA-NCS, is a good bifunctional chelating agent that can be used for protein-based radiopharmaceutical using lanthanides such as (177)Lu and (90)Y. The prepared (177)Lu-cys-DTPA-NCS-cetuximab can be used for the diagnosis and treatment of human colorectal tumor. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Does tumoral {sup 111}In-ibritumomab accumulation correlate with therapeutic effect and outcome in relapsed or refractory low-grade B-cell lymphoma patients undergoing {sup 90}Y-ibritumomab radioimmunotherapy?

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Koichiro; Shinozaki, Kenji [National Kyushu Cancer Center, National Hospital Organization, Department of Radiology, Minami-ku, Fukuoka (Japan); Choi, Ilseung; Uike, Naokuni [National Kyushu Cancer Center, National Hospital Organization, Division of Hematology, Minami-ku, Fukuoka (Japan); Nakagawa, Makoto [PET Imaging Center, Koga Hospital 21, Kurume (Japan)

    2014-12-15

    The aim of this study was to determine whether tumoral {sup 111}In-ibritumomab accumulation on pre-treatment imaging correlates with therapeutic responses and progression-free survival (PFS) in patients with non-Hodgkin's lymphoma (NHL) undergoing {sup 90}Y-ibritumomab radioimmunotherapy (RIT). This was a retrospective study of 39 patients with low-grade B-cell NHL treated with RIT. We classified the patients into positive and negative groups according to the presence or absence of tumoral {sup 111}In-ibritumomab accumulation on pre-treatment {sup 111}In-ibritumomab examinations. We then determined the correlation between the {sup 111}In-ibritumomab imaging findings and the patients' therapeutic responses and PFS. Tumoral {sup 111}In-ibritumomab accumulation was positive in 64.1 % and negative in 35.9 % of the patients. The {sup 111}In-positive patients had a significantly higher overall response rate (ORR) compared to the {sup 111}In-negative patients (100.0 % vs. 78.6 %, p = 0.02). The {sup 111}In-negative patients with advanced disease (stages III/IV) had a significantly lower ORR (40 %) and a significantly higher rate of progressive disease (40.0 %) compared to those of the {sup 111}In-negative patients with limited disease (stages I/II) (100 % and 0 %, p = 0.009 each). However, these two groups had similar 2-year PFS rates (65.0 % vs. 50.0 %, p = 0.80). {sup 111}In-ibritumomab imaging findings seem to correlate with ORR and the progressive disease rate after RIT, but not with PFS. (orig.)

  2. Study of influence of plastic scintillators thicknesses to detect Beta particles and Gamma radiation by means of spectral analysis of {sup 90}Sr, {sup 90}Y and {sup 137}Cs sources

    Energy Technology Data Exchange (ETDEWEB)

    Cardenas, Jose Patricio Nahuel; Filho, Tufic Madi; Pereira, Maria da Conceicao Costa; Santos, Brianna B. dos; Correa, Eduardo de L.; Santos, Lucas Rodrigues dos; Lopes, Anderson Figueredo; Silva, Alexandre F.P. da; Santos, Diogo F. dos; Camilo, Douglas de S.; Purgato, Rafael T.; Aredes, Vitor O.G. [Nuclear and Energy Research Institute, IPEN-CNEN/SP, Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP, Av. Prof. Lineu Prestes 2242 Cid Universitaria CEP: 05508-000- Sao Paulo-SP (Brazil)

    2015-07-01

    The Nuclear and Energy Research Institute - IPEN, offers post-graduate programs, namely: Nuclear Technology - Applications (TNA), Nuclear Technology - Materials (TNM), Nuclear Technology - Reactors (TNR). The Institute programs mission is to form expert technicians, physicists and engineers with a strong knowledge in their discipline to work in the nuclear area. The course: 'Theoretical Fundamentals and Practices of the Instrumentation used in Nuclear Data Acquisition' covers the use of laboratory nuclear instrumentation and the accomplishment of experiments to obtain nuclear parameters. One of these experimental exercises is object of this work: 'Study of influence of plastic scintillators to detect Beta particles and Gamma radiation by means of spectral analysis of {sup 90}Sr, {sup 90}Y and {sup 137}Cs sources'. The use of scintillators plastic for the detection has the advantage of low cost, high mechanical strength, is not hygroscopic and can be manufactured in large volumes. This work aims to present the analysis of relative efficiency of detection of plastic scintillators of various thicknesses for beta particles and gamma radiation by the spectrum of {sup 137}Cs and {sup 90}Sr. Due to lack of resolution of the detectors plastic scintillators we worked with relative efficiency. The evaluation was done by reading deposited energy, using the software MAESTRO, for each detector thickness. For beta particles was observed an ideal thickness around 3 mm and the better photon efficiency was observed with increasing the thickness of the detector. The present experiment does not intend to establish a new technique for this subject: it solely aims student's practical exercises in nuclear properties of elements and detectors being part of the nuclear experimental course. (authors)

  3. Thermoluminescent characteristics (TL) of K{sub 2}F{sub 5}: Y{sub 0.99} Tb{sub 0.01} irradiated with beta particles of {sup 90}Sr/{sup 90} Y; Caracteristicas termoluminiscentes (TL) de K{sub 2}F{sub 5}: Y{sub 0.99} Tb{sub 0.01} irradiado con particulas beta de {sup 90}Sr/{sup 90} Y

    Energy Technology Data Exchange (ETDEWEB)

    Baillet, C.; Azorin, J.; Rivera, T. [Dep. de Fisica, UAM-I, 09340 Mexico D.F. (Mexico)

    2005-07-01

    In this work the results of studying the thermoluminescent characteristics of the K{sub 2}F{sub 5}: Y{sub 0.99} Tb{sub 0.01} are presented. The material was characterized irradiating samples of K{sub 2}F{sub 5}: Y{sub 0.99}Tb{sub 0.01} in powder with beta radiation of {sup 90}Sr/{sup 90}Y. The studied characteristics were TL curve, response reproducibility, TL response in function of the dose and fading of the information. The samples exhibited a thermoluminescent curve (TL) with two very defined peaks centered respectively in 167 and 307 C. The TL response of the samples under the action of the beta radiation after 10 cycles (thermal erased, irradiation and reading of the samples) presented a standard deviation of 3.09%. The TL response of K{sub 2}F{sub 5}: Y{sub 0.99} Tb{sub 0.01} in function of the absorbed dose of beta radiation resulted lineal in the interval of 3 mGy to 1.29 Gy. The fading of the information contained in the samples of K{sub 2}F{sub 5}: Y{sub 0.99} Tb{sub 0.01} was of 40% in the first 10 minutes, which is due to the first peak. The obtained results suggest that the TL material resulted as promissory for its possible use as thermoluminescent dosemeter of beta radiation using the second peak of its TL curve like dosimetric peak. (Author)

  4. Long-term results of PRRT in advanced bronchopulmonary carcinoid

    Energy Technology Data Exchange (ETDEWEB)

    Mariniello, Annapaola; Bodei, Lisa; Baio, Silvia Melania; Gilardi, Laura; Colandrea, Marzia; Papi, Stefano; Grana, Chiara Maria [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Tinelli, Carmine [IRCCS Foundation Policlinico San Matteo, Epidemiology and Biometric Unit, Pavia (Italy); Valmadre, Giuseppe [Presidio Ospedaliero E. Morelli AOVV, Sondalo (Italy); Fazio, Nicola [European Institute of Oncology, Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, Milan (Italy); Galetta, Domenico [European Institute of Oncology, Thoracic Surgery Division, Milan (Italy); Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy)

    2016-03-15

    Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT. We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols ({sup 90}Y-DOTATOC vs. {sup 177}Lu-DOTATATE vs. {sup 90}Y-DOTATOC + {sup 177}Lu-DOTATATE) were compared with regard to their efficacy and tolerability. The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The {sup 177}Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4 %). Morphological responses (partial responses + minor responses) were obtained in 26.5 % of the cohort and were associated with longer OS and PFS. The {sup 90}Y-DOTATOC + {sup 177}Lu-DOTATATE protocol provided the highest response rate (38.1 %). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with {sup 90}Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity. In a large cohort of patients with advanced BPC treated in a ''real-world'' scenario and followed up for a median of 45.1 months (range 2 - 191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite

  5. Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

    Science.gov (United States)

    Severi, Stefano; Grassi, Ilaria; Nicolini, Silvia; Sansovini, Maddalena; Bongiovanni, Alberto; Paganelli, Giovanni

    2017-01-01

    Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs]) and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%–70% of all NENs). They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases). Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon). Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors. Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided. PMID:28203088

  6. Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available 177Lu-DOTA-HH1 (177Lu-HH1 is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1 and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1.

  7. Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma

    Science.gov (United States)

    Repetto-Llamazares, Ada H. V.; Larsen, Roy H.; Patzke, Sebastian; Fleten, Karianne G.; Didierlaurent, David; Pichard, Alexandre; Pouget, Jean Pierre; Dahle, Jostein

    2015-01-01

    177Lu-DOTA-HH1 (177Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab) and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1) and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1. PMID:26066655

  8. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2015-07-01

    Full Text Available Objective(s: Peptide Receptor Radionuclide Therapy (PRRT with yttrium-90 (90Y and lutetium-177 (177Lu-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system.Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany. Sterile, GMP-certified, no-carrier added (NCA 177Lu was used with GMPcertifiedpeptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods.Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05% and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5% for this period.Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

  9. Self-assembled monolayers on gold for the fabrication of radioactive stents

    NARCIS (Netherlands)

    Bommel, van Kjeld J.C.; Friggeri, Arianna; Mateman, Dorine; Geurts, Frank A.J.; Leerdam, Kees G.C.; Verboom, Willem; Veggel, van Frank C.J.M.; Reinhoudt, David N.

    2001-01-01

    An innovative and easily applicable method for the fabrication of radioactive stents, to be used for the treatment of restenosis, is presented. By incorporating the b-emitting radioisotopes 186Re, 188Re, 90Y, or 32P into sulfur-containing adsorbates, it becomes possible to cover a gold surface with

  10. A preclinical simulated dataset of S-values and investigation of the impact of rescaled organ masses using the MOBY phantom

    Science.gov (United States)

    Kostou, Theodora; Papadimitroulas, Panagiotis; Loudos, George; Kagadis, George C.

    2016-03-01

    Nuclear medicine and radiation therapy, although well established, are still rapidly evolving, by exploiting animal models, aiming to define precise dosimetry in molecular imaging protocols. The purpose of the present study was to create a dataset based on the MOBY phantom for the calculation of organ-to-organ S-values of commonly used radionuclides. S-values of most crucial organs were calculated using specific biodistributions with a whole-body heterogeneous source. In order to determine the impact of the varying organs’ size on the S-values, and based on the fact that the anatomic properties of the organs are correlated with S-values, dosimetric calculations were performed by simulating the MOBY-version 2 model with different whole-body masses. The GATE Monte Carlo simulation toolkit was used for all simulations. Two mouse models of different body masses were developed to calculate the S-values of eight commonly used radioisotopes in nuclear imaging studies, namely 18F, 68Ga, 131I, 111In, 177Lu, and 99mTc, 90Y and 188Re. The impact of modified mass of the source organs in S-values was investigated with 18F, and 90Y in five different scalings of the source organs. Based on realistic preclinical exams, three mouse models, 22, 28 and 34 g, were used as input in the GATE simulator based on realistic preclinical exams to calculate the S-values of the six radioisotopes used. Whole body activity distributions were used as the source organ. The simulation procedure was validated in terms of extracting individual organ-to-organ S-values, and consequently in calculating the new S-values using a heterogeneous activity distribution as a source. The calculation was validated with 18F source in a 30 g mouse model. For the generation of the new S-values with heterogeneous activity sources, four organs were used for the calculation of a single S-value. The absorbed doses per organ were compared with previously published reports. The validation procedure of 18F indicates

  11. In vivo comparative study of hydroxyapatite labeled with different radioisotopes: evaluation of the scintigraphic images

    Energy Technology Data Exchange (ETDEWEB)

    Couto, Renata Martinussi; Barboza, Marycel Figols de; Souza, Adriano Aparecido de; Muramoto, Emiko; Mengatti, Jair; Araujo, Elaine Bortoleti de, E-mail: rmcouto@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia

    2008-07-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints that is characterized by the inflammation and proliferation of synovial tissues. Approximately 3% of the adult population in the world is affected by this disease which causes pain, joint immobility and disability. Adyo synovectomy (RSV) is a radiotherapeutic modality where a b--emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy in the treatment of RA and other inflammatory arthropathies. There are several radionuclides available for this purpose such as {sup 177}Lu, {sup 90}Y, {sup 153}Sm, {sup 165}Dy, and {sup 166}Ho. Hydroxyapatite (HA) is one of the preferred particulates for this application because it is the major chemical constituent of skeletal bone and it is converted into Ca and PO4 ions in the body. In addition HA is completely eliminated over a period of six weeks. The aim of this work is to compare the in vivo stability of hydroxyapatite labeled with {sup 177}Lu, {sup 90}Y and {sup 153}Sm in order to determine the influence of the radionuclide on biological pattern. In biological studies, 100mL of labeled HAs suspended in normal saline were injected into normal knee joints of Wistar rats and the retention of the activity into the synovium was determined. Labeled particles were also injected by intravenous and intramuscular administration, to verify the biodistribution in the case of an eventual leakage of the products from the joint. Sequential scintigraphic images were acquired from 1 hour to 7 days p.i. after anesthetizing the animals with ketamine. Hydroxyapatite was radiolabeled by all radionuclides with high yield. {sup 177}Lu-HA, {sup 90}Y-HA and {sup 153}Sm-HA were retained in the joint for 7 days, showing

  12. Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14

    Science.gov (United States)

    Hertzberg, Mark; Gandhi, Maher K.; Trotman, Judith; Butcher, Belinda; Taper, John; Johnston, Amanda; Gill, Devinder; Ho, Shir-Jing; Cull, Gavin; Fay, Keith; Chong, Geoff; Grigg, Andrew; Lewis, Ian D.; Milliken, Sam; Renwick, William; Hahn, Uwe; Filshie, Robin; Kannourakis, George; Watson, Anne-Marie; Warburton, Pauline; Wirth, Andrew; Seymour, John F.; Hofman, Michael S.; Hicks, Rodney J.

    2017-01-01

    In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan–BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17–20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3–4, 54% bulk, and 54% International Prognostic Index 3–5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results

  13. Mensuration of equivalent dose with personal dosemeters and instruments of radiological protection in the new operative quantities ICRU, for external fields of beta radiation. Part II. I study of the angular response of personal dosemeters TLD-100 in secondary patron fields of beta radiation ({sup 90}Sr / {sup 90}Y); Medicion de dosis equivalente con dosimetros personales e instrumentos de proteccion radiologica en las nuevas magnitudes operativas ICRU, para campos de radiacion beta externos. Parte II. Estudio de la respuesta angular de dosimetros personales TLD-100 en campos patrones secundarios de radiacion beta ({sup 90}Sr/{sup 90}Y)

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, J.T. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    1994-01-15

    The objective of this work is to carry out one of the possible ones test type for personal dosemeters TLD, under the recomendations of the ICRU 39, ICRU 43 and the draft of the norm ISO 6980,(1992), with the purpose of verifying the capacity of these detectors to carry out the operative unit: H' (0.07;{alpha}). Since H' (O. 07;{alpha}) this defined one in an expanded field, one of these tests type consist on determining the angular response of these detectors. 20 personal dosemeters TLD-100 was used, (card marks: Harshaw, Model: G-1, with two glasses of TLD-100 absorbed in teflon; the portadosemeters has two windows, a free one and another with a filter of Pb of 171.0 mg cm{sup -2}); these dosemeters they were previously selected, [to see, {sup S}tudy of the Homogeneity of the response of Personal Dosemeters (Cards G-l, TLD-100) in Radiation of Countrysides of {sup 60}Co{sup ,} J.T. Alvarez R. Technician Report GSR/IT/0001/94].The irradiations to effectued in secondary countryside of radiation beta of {sup 90}Sr/{sup 90}Y. The study was undertaken by means of an experimental design of blocks random that contemplate the following variables: intensity of the radiation source, (1850 MBq and 74 MBq); position of irradiation, (four positions); incidence of angle of the radiation (0, 15, 30, 45, 60 and 75 grades) and the absorbed dose in air, (0.005, 0.010, 0.020, 0.050 and 0.100 Gy). Then null hypothesis it was to suppose that there was not difference among the stockings of each treatment, to used the statistical of Duncan to carry out tests of stockings at a level of significance of 5%.These tests of stockings throw the following results in those variables of the experimental design: The irradiations carried out so much with the source pattern secondary of {sup 90}Sr/{sup 90}Y of 1850 MBq and of 74 MBq, they are equivalent reason why they can be used indistinctly. The responses of each one of the glasses of the card are strongly anisotropic for each glass

  14. Measurement of dose speed absorbed in depth imparted by sources external secondary patterns of beta radiation. Part 1 Measurement of dose speed absorbed in the surface of soft fabric for isotopes of {sup 90}Sr/{sup 90}Y, {sup 147}Pm and {sup 204}TI; Medicion de rapidez de dosis absorbida en profundidad impartida por fuentes patrones secundarios de radiacion beta externos. Parte 1. Medicion de rapidez de dosis absorbida en la superficie de tejido blando para isotopos de {sup 90}Sr/{sup 90}Y, {sup 147}Pm y {sup 204}TI

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, J.T. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    1993-01-15

    The dose speed was measured absorbed for depth zero, (superficial) in soft equivalent fabric, for the secondary pattern{sup s} four sources of beta radiation, (Nr. 86): {sup 90}Sr/{sup 90}Y, (1850 MBq and 74 MBq respectively); {sup 147}Pm, (518 MBq) and {sup 204}TI, (18.5 MBq). The measurement is carried out to different distances of source-detecting separation, (11.0, 30.0 and 50.0 cm for the source of 1850 MBq, 30.0 cm for that of 74 MBq; 11.00 cm for the source of {sup 147}Pmand to contact for all the sources); maintaining the radiation sheaf aligned the one axis of symmetry of the detector, ({alpha} 0 degrees). The detector employed was a extrapolation chambers of variable electrodes and electrode fixed collector, (30 mm of diameter). In accordance with the principle of Bragg-Gray the volume of the chambers is varied and they register the variations of the current of collected ionization, correcting until for a maximum of thirteen correction factors that take into account the deviation to the suppositions that it establishes this principle. The certain values of the speed of superficial absorbed dose are in the following intervals: {sup 90}Sr/{sup 90}Y, (1850 MBq, 0.0, 11.0, 30.0 and 50.0 cm): 43.164 mGy S-t, 0.544 mGy s-1 ,0.075 mGy s{sup -1} and 0.027 mGy s{sup -1}, respectively, with a Global Analysis of the order of 1.17%, 1.17%, 1.14% and 1.66%, K J; {sup 90}Sr / {sup 90}Y, (74 MBq, 0.0 and 30 cm): 1.536 mGy s{sup -1} and 0.002 mGy s{sup -1}, with Global Analysis of 1.19.0% and 5.22%, (K = 1) respectively, for the {sup 147}Pm, (0.0 and 11.0 in the interval of: 0.36 {mu}Gy s{sup -1} and 0.43 {mu}Gy s{sup -1}, with one Global Analysis of 1 .42% and 4.28%, (K = 1), respectively; and finally for the {sup 204}TI, (0.0 cm) in the interval of 0.10 {mu}Gy s{sup -1} with a Global Analysis of 1.27%. He calculates of the Global Analysis one carries out of agreement with those recommendations of the BIPM. In all the cases of source-detecting arrangement with

  15. Comparison of 111In-[DTPA0]Octreotide Versus Non Carrier Added 177Lu- [DOTA0,Tyr3]-Octreotate Efficacy in Patients With GEP-NET Treated Intra-arterially for Liver Metastases.

    Science.gov (United States)

    Limouris, G S; Poulantzas, V; Trompoukis, N; Karfis, I; Chondrogiannis, S; Triantafyllou, N; Gennimata, V; Moulopoulou, L-E; Patsouris, E; Nikou, G; Michalaki, V; Fragulidis, G; Paphiti, M; McCready, R V; Colletti, P M; Cook, G J; Rubello, D

    2016-03-01

    In patients with progre