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Sample records for cancerhapatocellular carcinomeby holmium-166

  1. Studies on therapeutic method of liver cancer(hapatocellular carcinome)by Holmium-166 radionuclide

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    Lee, Jong Tae; Yoo, H. S.; Kim, M. J.; Han, K. H.; Park, C. I. [Yonsei University Medical College, Seoul (Korea, Republic of)

    1997-07-01

    As the study of radioactive nuclide, Holmium-166 in the treatment of liver cancer(hepatocellular carcinoma), this study was performed under the base of animal experimental. Using dog liver, percutaneous injection of Ho-166 MAA or chitosan with premade dose was done under the ultrasound guidance. Continuously the same procedure as previous one was performed in the skin hapatoma, which was developed by the injection of hepatocellular carcinoma cell in the nude mouse, In case of injected normal liver of dog, imaging study including ultrasound, CT and MRI was done in order to evaluate effect of Ho-166 and pathologic reaction. The result showed well defined nectosis of normal liver as well as skin hepatoma. The area of nectosis is dependent on the dose of injected Ho-166. Generally, pathologic reaction is tissue coagulation nectosis, Ho-166 particles, fibrosis and hemorrhage. In the clinical study, 50 patients with hapatoma was selected for this study under the agreement of patient. Under ultrasound guidance percutaneous injection of Ho-166 Maa or chitosan to tumor was performed and follow-up study was extended from 6 to 12 month. The result showed that 64% of patient were completely treated. Overall, the effect of treatment could be obtained in 41 patient (82%) among 50 hepatoma patient. Conclusively Ho-166 is thought to be a compromising agent in the treatment of hepatocellular carcinoma and one of therapeutic modality, if it is established internally and world-wide. In the future, the popular percutaneous ethanol injection method will be replaced to this method. 19 refs., 1 tabs., 14 figs. (author)

  2. Holmium-166 therapy of malignant and benign diseases

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    Park, C.H. [Ajou Univ. School of Medicine, Suwon (Korea)

    1999-07-01

    Holmium-166 (Ho-166), one of the lanthanide radionuclides and produced upon neutron irradiation of naturally abundant Ho-165, is an almost ideal radionuclide for therapeutic purposes. The reasons for this are: (1) it is a strong beta emitter (Emax = 1.86 MeV) with maximum range in soft-tissue of 8.4 mm, (2) it has a short physical half-life of 26.9 hours, (3) it emits a gamma photon (81 keV, 5.4%) that can be used for external imaging of post-therapy monitoring purpose. Clinical trials of Ho-166 therapy for various malignancies and benign conditions are under way in Korea, {sup 166}Ho(NO{sub 3}) solution is applied into the balloon following percutaneous transfemoral coronary angioplasty (PTCA) in an attempt to inhibit neointimal hyperplasia incident to ballooning injury. Chitosan obtained by deacetylation of naturally abundant chitin is complexed with Ho-166 by mixing acidic chitosan solution at a room temperature with higher than 99% labelling yield. The Ho-166 complex is stable in vitro and vivo. Another benign condition, rheumatoid joint disease, is treated by local administration of the agent into the knee joint for radionuclide synovectomy. Malignant conditions being treated with Ho-166-CHICO (chitosan complex) include cystic brain tumours, malignant ascites and pleural effusion, hepatocellular carcinomas, recurrent melanoma and recurrent rectal carcinomas. Our clinical experience with Ho-166 or Ho-166-CHICO therapy is presented. (orig.)

  3. Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(l-lactic acid) microspheres in healthy pigs

    NARCIS (Netherlands)

    Vente, M.A.D.; Nijsen, J.F.W.; De Wit, T.C.; Seppenwoolde, J.H.; Krijger, G.C.; Seevinck, P.R.; Huisman, A.; Zonneneberg, B.A.; Van den Ingh, T.S.G.A.M.; Van het Schip, A.D.

    2008-01-01

    Purpose The aim of this study is to evaluate the toxicity of holmium-166 poly(l-lactic acid) microspheres administered into the hepatic artery in pigs. Methods Healthy pigs (20–30 kg) were injected into the hepatic artery with holmium-165-loaded microspheres (165HoMS; n = 5) or with holmium-166-l

  4. Quantitative Monte Carlo-based holmium-166 SPECT reconstruction

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    Elschot, Mattijs; Smits, Maarten L. J.; Nijsen, Johannes F. W.; Lam, Marnix G. E. H.; Zonnenberg, Bernard A.; Bosch, Maurice A. A. J. van den; Jong, Hugo W. A. M. de [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht (Netherlands); Viergever, Max A. [Image Sciences Institute, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht (Netherlands)

    2013-11-15

    Purpose: Quantitative imaging of the radionuclide distribution is of increasing interest for microsphere radioembolization (RE) of liver malignancies, to aid treatment planning and dosimetry. For this purpose, holmium-166 ({sup 166}Ho) microspheres have been developed, which can be visualized with a gamma camera. The objective of this work is to develop and evaluate a new reconstruction method for quantitative {sup 166}Ho SPECT, including Monte Carlo-based modeling of photon contributions from the full energy spectrum.Methods: A fast Monte Carlo (MC) simulator was developed for simulation of {sup 166}Ho projection images and incorporated in a statistical reconstruction algorithm (SPECT-fMC). Photon scatter and attenuation for all photons sampled from the full {sup 166}Ho energy spectrum were modeled during reconstruction by Monte Carlo simulations. The energy- and distance-dependent collimator-detector response was modeled using precalculated convolution kernels. Phantom experiments were performed to quantitatively evaluate image contrast, image noise, count errors, and activity recovery coefficients (ARCs) of SPECT-fMC in comparison with those of an energy window-based method for correction of down-scattered high-energy photons (SPECT-DSW) and a previously presented hybrid method that combines MC simulation of photopeak scatter with energy window-based estimation of down-scattered high-energy contributions (SPECT-ppMC+DSW). Additionally, the impact of SPECT-fMC on whole-body recovered activities (A{sup est}) and estimated radiation absorbed doses was evaluated using clinical SPECT data of six {sup 166}Ho RE patients.Results: At the same noise level, SPECT-fMC images showed substantially higher contrast than SPECT-DSW and SPECT-ppMC+DSW in spheres ≥17 mm in diameter. The count error was reduced from 29% (SPECT-DSW) and 25% (SPECT-ppMC+DSW) to 12% (SPECT-fMC). ARCs in five spherical volumes of 1.96–106.21 ml were improved from 32%–63% (SPECT-DSW) and 50%–80

  5. Preclinical studies on holmium-166 poly(L-lactic acid) microspheres for hepatic arterial radioembolization

    NARCIS (Netherlands)

    Vente, M.A.D.

    2009-01-01

    Hepatic arterial radioembolization with radioactive holmium-166 loaded poly(L-lactic acid) microspheres (166Ho-PLLA-MS) constitutes the subject of this thesis. This technique represents a potential treatment option for patients with unresectable liver malignancies. 166Ho-PLLA-MS are believed to be a

  6. Preclinical studies on holmium-166 poly(L-lactic acid) microspheres for hepatic arterial radioembolization

    OpenAIRE

    Vente, M.A.D.

    2009-01-01

    Hepatic arterial radioembolization with radioactive holmium-166 loaded poly(L-lactic acid) microspheres (166Ho-PLLA-MS) constitutes the subject of this thesis. This technique represents a potential treatment option for patients with unresectable liver malignancies. 166Ho-PLLA-MS are believed to be an improvement over the already clinically applied yttrium-90 microspheres (90Y-MS) due to the multimodality imaging properties of holmium, specifically its capability to be visualized by gamma scin...

  7. Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(L-lactic acid) microspheres in healthy pigs

    OpenAIRE

    Vente, M.A.D.; Nijsen, J. F. W.; De Wit, T.C.; Seppenwoolde, J.H.; Krijger, G. C.; Seevinck, P. R.; Huisman, Albert; Zonnenberg, Bernard A.; Ingh, T.S.G.A.M. van den; Schip, A.D. van het

    2008-01-01

    Purpose: The aim of this study is to evaluate the toxicity of holmium-166 poly(L-lactic acid) microspheres administered into the hepatic artery in pigs. Methods: Healthy pigs (20–30 kg) were injected into the hepatic artery with holmium-165-loaded microspheres (165HoMS; n=5) or with holmium-166-loaded microspheres (166HoMS; n=13). The microspheres’ biodistribution was assessed by single-photon emission computed tomography and/or MRI. The animals were monitored clinically, biochemically, and (...

  8. Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(l-lactic acid) microspheres in healthy pigs

    OpenAIRE

    Vente, M.A.D.; Nijsen, J. F. W.; De Wit, T.C.; Seppenwoolde, J.H.; Krijger, G. C.; Seevinck, P. R.; Huisman, A.; Zonneneberg, B.A.; van den Ingh, T.S.G.A.M.; van het Schip, A. D.

    2008-01-01

    Purpose The aim of this study is to evaluate the toxicity of holmium-166 poly(l-lactic acid) microspheres administered into the hepatic artery in pigs. Methods Healthy pigs (20–30 kg) were injected into the hepatic artery with holmium-165-loaded microspheres (165HoMS; n = 5) or with holmium-166-loaded microspheres (166HoMS; n = 13). The microspheres’ biodistribution was assessed by single-photon emission computed tomography and/or MRI. The animals were monitored clinically, biochemically, and...

  9. Holmium-166 poly(L-lactic acid) microsphere radioembolisation of the liver : technical aspects studied in a large animal model

    NARCIS (Netherlands)

    Vente, M A D; de Wit, T C; van den Bosch, M A A J; Bult, W; Seevinck, P R; Zonnenberg, B A; de Jong, H W A M; Krijger, G C; Bakker, C J G; van het Schip, A D; Nijsen, J F W

    2010-01-01

    OBJECTIVE: To assess the accuracy of a scout dose of holmium-166 poly(L-lactic acid) microspheres ((166)Ho-PLLA-MS) in predicting the distribution of a treatment dose of (166)Ho-PLLA-MS, using single photon emission tomography (SPECT). METHODS: A scout dose (60 mg) was injected into the hepatic arte

  10. Radiation dose measurements for staff members involved in holmium-166 preclinical trial

    International Nuclear Information System (INIS)

    Aim: Neutron-activated holmium-166 (166Ho) is an excellent radionuclide for internal radiation therapy (Eβmax = 1.84 MeV) with an appropriate half-life (26.8 h), which emits photons (81 keV, 6.2%) suitable to be detected by gamma cameras. Preparing and injecting radiopharmaceuticals containing beta/gamma emitting holmium-166 implies a risk of exceeding the upper limit for skin and hand radiation equivalent doses (500 mSv/an). This study was aimed to estimate the whole body and finger exposure for staff responsible for dose preparation, dose dispensing, and dose injection of holmium-166 therapy. Methods: To measure the finger dose from external exposure, all staff members wore TLD dosimeters. Personal dose equivalents Hp(10) were measured using electronic personal dosimeters (EPD MK2, Thermo Fischer Scientific) placed on the left side of the chest. During our study, staff members administered more than 40 166Ho-based therapies for preclinical trial. Appropriate radiation safety procedures and shielding were applied at each stage. Results: In this study, the whole body doses were 2.80 ± 1.56 nSv MBq−1 for one 166Ho-therapy preparation/formulation, and 2.68 ± 1.70 nSv MBq−1 for one intravenous injection. Maximum finger doses were 2.9 ± 0.2 μSv MBq−1 and 2.5 ± 0.3 μSv MBq−1 for preparation and injection, respectively (activities injected: 72 ± 3 MBq). Conclusion: Extrapolated annual doses from 300 166Ho radionuclide therapies were lower than the annual limit doses for skin and the whole body, 500 mSv and 20 mSv, respectively, reported in the European Directive EURATOM 96/29 when applying appropriate radiation protection standards. However, these doses have to be added to other diagnostic or therapeutic protocols, performed in preclinical facilities. - Highlights: • Radiation measurements for staff performing 166 Holmium radionuclide therapy was evaluated. • Hand exposure was estimated using TLD dosimeter. • Whole body doses was evaluated using EPD

  11. Feasibility of Endovascular Radiation Therapy Using Holmium-166 Filled Balloon Catheter in a Swine Hemodialysis Fistula Model: Preliminary Results

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    Won, Jong Yun; Lee, Kwang Hun; Lee, Do Yun [Dept. of Radiology, Research Institute of Radiological Science, Yensei University College of Medicine, Seoul (Korea, Republic of); Kim, Myoung Soo [Dept. of Radiology, Yensei University College of Medicine, Seoul (Korea, Republic of); Kang, Byung Chul [Dept. of Radiology, Internal Medicine, EwhaWoman' s University School of Medicine, Seoul (Korea, Republic of); Kim, Seung Jung [Dept. of Internal Medicine, EwhaWoman' s University School of Medicine, Seoul (Korea, Republic of)

    2011-08-15

    To describe how to make a swine hemodialysis fistula model and report our initial experience to test the feasibility of endovascular radiation therapy with Holmium-166 filled balloon catheters. The surgical formation of arterio-venous fistula (AVF) was performed by end-to-side anastomosis of the bilateral jugular vein and carotid artery of 6 pigs. After 4 weeks, angiograms were taken and endovascular radiation was delivered to the venous side of AVF with Holmium-166 filled balloon catheters. Pigs were sacrificed 4 weeks after the radiation and AVFs were harvested for histological examination. All animals survived without any morbidity during the experimental periods. The formation of fistula on the sides of necks was successful in 11 of the 12 pigs (92%). One AVF failed from the small jugular vein. On angiograms, 4 of the 11 AVFs showed total occlusion or significant stenosis and therefore, endovascular radiation could not be performed. Of 7 eligible AVFs, five underwent successful endovascular radiation and two AVFs did not undergo radiation for the control. Upon histologic analysis, one non-radiated AVF showed total occlusion and others showed intimal thickening from the neointimal hyperplasia. Formation of the swine carotid artery-jugular vein hemodialysis fistula model was successful. Endovascular radiation using a Holmium-166 filled balloon catheter was safe and feasible.

  12. Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(l-lactic acid) microspheres in healthy pigs

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    Vente, M.A.D.; Nijsen, J.F.W.; Wit, T.C. de; Schip, A.D. van het [University Medical Center Utrecht, Department of Nuclear Medicine, P.O. Box 85500, Utrecht (Netherlands); Seppenwoolde, J.H.; Seevinck, P.R. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Krijger, G.C. [Delft University of Technology, Department of Radiation, Radionuclides and Reactors, Faculty of Applied Sciences, Delft (Netherlands); Huisman, A. [University Medical Center Utrecht, Department of Clinical Chemistry and Haematology, Utrecht (Netherlands); Zonnenberg, B.A. [University Medical Center Utrecht, Department of Internal Medicine, Utrecht (Netherlands); Ingh, T.S.G.A.M. van den [TCCI Consultancy B.V., P.O. Box 85032, Utrecht (Netherlands)

    2008-07-15

    The aim of this study is to evaluate the toxicity of holmium-166 poly(l-lactic acid) microspheres administered into the hepatic artery in pigs. Healthy pigs (20-30 kg) were injected into the hepatic artery with holmium-165-loaded microspheres ({sup 165}HoMS; n = 5) or with holmium-166-loaded microspheres ({sup 166}HoMS; n = 13). The microspheres' biodistribution was assessed by single-photon emission computed tomography and/or MRI. The animals were monitored clinically, biochemically, and ({sup 166}HoMS group only) hematologically over a period of 1 month ({sup 165}HoMS group) or over 1 or 2 months ({sup 166}HoMS group). Finally, a pathological examination was undertaken. After microsphere administration, some animals exhibited a slightly diminished level of consciousness and a dip in appetite, both of which were transient. Four lethal adverse events occurred in the {sup 166}HoMS group due either to incorrect administration or comorbidity: inadvertent delivery of microspheres into the gastric wall (n = 2), preexisting gastric ulceration (n = 1), and endocarditis (n = 1). AST levels were transitorily elevated post-{sup 166}HoMS administration. In the other blood parameters, no abnormalities were observed. Nuclear scans were acquired from all animals from the {sup 166}HoMS group, and MRI scans were performed if available. In pigs from the {sup 166}HoMS group, atrophy of one or more liver lobes was frequently observed. The actual radioactivity distribution was assessed through ex vivo {sup 166m}Ho measurements. It can be concluded that the toxicity profile of HoMS is low. In pigs, hepatic arterial embolization with {sup 166}HoMS in amounts corresponding with liver-absorbed doses of over 100 Gy, if correctly administered, is not associated with clinically relevant side effects. This result offers a good perspective for upcoming patient trials. (orig.)

  13. Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study

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    Nijsen, F.; Rook, D.; Zonnenberg, B.; Klerk, J. de; Rijk, P. van; Schip, F. van het [Dept. of Nuclear Medicine, University Medical Center, Utrecht (Netherlands); Brandt, C. [Animal Inst., Utrecht Univ. (Netherlands); Meijer, R. [Dept. of Radiology, Univ. Medical Center, Utrecht (Netherlands); Dullens, H. [Dept. of Pathology, Univ. Medical Center, Utrecht (Netherlands); Hennink, W. [Dept. of Pharmaceutics, Utrecht Univ. (Netherlands)

    2001-06-01

    Intra-arterial administration of beta-emitting particles that become trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-{mu}m poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was {<=}0.1%ID/g, with incidental exceptions in the lungs and stomach. Very little {sup 166}Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6.1{+-}2.9 for rats with tumour (n=15) versus 0.7{+-}0.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use of adrenaline. Histological analysis showed that five times as many large (>10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma. (orig.)

  14. Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial

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    de Jong Hugo WAM

    2010-06-01

    Full Text Available Abstract Background Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid microspheres ( 166Ho-PLLA-MS have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases. Methods The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively. The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution. Discussion This will be the first clinical study on 166Ho-RE. Based on

  15. MR evaluation of radiation synovectomy of the knee by means of intra-articular injection of holmium-166-chitosan complex in patients with rheumatoid arthritis: results at 4-month follow-up

    International Nuclear Information System (INIS)

    To determine whether MRI is able to demonstrate the effect of radiation synovectomy after the intra-articular injection of holmium-166-chitosan complex for the treatment of rheumatoid arthritis of the knee. Fourteen patients aged 36-59 years were treated with 10-20 mCi of holmium-166-chitosan complex. A criterion for inclusion in this study was the absence of observable improvement after 3- or more months of treatment of the knee with disease-modifying anti-rheumatic drugs. MR images were acquired both prior to and 4-months after treatment. Clinical evaluation included the use of visual analog scales to assess pain, and the circumference of the knee and its range of motion were also determined. MR evaluation included measurement of the volume of synovial enhancement and wall thickness, the amount of joint effusion, and quantifiable scoring of bone erosion, bone edema and lymph nodes. Visual analog scale readings decreased significantly after radiation synovectomy (p<0.05). MRI showed that joint effusion decreased significantly (p<0.05), and that the volume of synovial enhancement tended to decrease, but to an insignificant extent (p=0.107). The decreased joint effusion noted at 4-month follow-up resulted from radiation synovectomy of the rheumatoid knee by means of intra-articular injection of holmium-166-chitosan complex

  16. A phase I/IIa study on intra-articular injection of holmium-166-chitosan complex for the treatment of knee synovitis of rheumatoid arthritis

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    Song, J.; Suh, C.H.; Park, Y.B.; Lee, S.H.; Lee, S.K. [Dept. of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea); Yoo, N.C. [Dept. of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea); Dept. of Clinical Pharmacology, Yonsei University College of Medicine, Seoul (Korea); Lee, J.D. [Dept. of Nuclear Medicine, Yonsei University College of Medicine, Seoul (Korea); Kim, K.H. [Dept. of Clinical Pharmacology, Yonsei University College of Medicine, Seoul (Korea)

    2001-04-01

    Previous animal studies have established that the intra-articular injection of holmium-166-chitosan complex (DW-166HC) causes effective necrosis of the inflamed synovium with little leakage of radioactivity from the injected joint. Based on these findings, we conducted a phase I/IIa study to examine the biodistribution of DW-166HC and to assess the safety of DW-166HC for the treatment of knee synovitis in patients with rheumatoid arthritis (RA). A total of 16 patients [1 man, 15 women; median age 49 (range 36-65) years] who had RA knee synovitis refractory to disease-modifying antirheumatic drug treatments of >3 months' duration were randomly assigned to three treatment groups with different radiation doses of DW-166HC: 370 MBq (n=6), 555 MBq (n=5) and 740 MBq (n=5). In each treatment group, blood and urine radioactivity were analysed by beta counter and biodistribution of the injected DW-166HC was evaluated using a gamma scan camera. Clinical assessment was done according to three variables (evaluation method): knee joint pain (visual analogue scale), range of motion (goniometry) and joint swelling (circumference of knee joint). The duration of follow-up observation was 3 months. Following the intra-articular injection of DW-166HC, the blood radioactivity was little changed from the baseline measurement and the accumulated radioactivity excreted in urine was minimal. Gamma scan study indicated that most of the injected radiochemical was localized within the injected joint cavity, and the extra-articular leakage was negligible at 24 h after the injection: brain, 0.3%; lung, 0.6%; abdomen, 0.7%; and pelvis, 0.8%. Major adverse events were transient post-injection knee joint pain and swelling. These results suggest that DW-166HC might be a safe agent for radiation synovectomy, particularly for the treatment of knee synovitis of RA, and further trials in a larger patient population are warranted to evaluate the therapeutic efficacy of DW-166HC. (orig.)

  17. A phase I/IIa study on intra-articular injection of holmium-166-chitosan complex for the treatment of knee synovitis of rheumatoid arthritis

    International Nuclear Information System (INIS)

    Previous animal studies have established that the intra-articular injection of holmium-166-chitosan complex (DW-166HC) causes effective necrosis of the inflamed synovium with little leakage of radioactivity from the injected joint. Based on these findings, we conducted a phase I/IIa study to examine the biodistribution of DW-166HC and to assess the safety of DW-166HC for the treatment of knee synovitis in patients with rheumatoid arthritis (RA). A total of 16 patients [1 man, 15 women; median age 49 (range 36-65) years] who had RA knee synovitis refractory to disease-modifying antirheumatic drug treatments of >3 months' duration were randomly assigned to three treatment groups with different radiation doses of DW-166HC: 370 MBq (n=6), 555 MBq (n=5) and 740 MBq (n=5). In each treatment group, blood and urine radioactivity were analysed by beta counter and biodistribution of the injected DW-166HC was evaluated using a gamma scan camera. Clinical assessment was done according to three variables (evaluation method): knee joint pain (visual analogue scale), range of motion (goniometry) and joint swelling (circumference of knee joint). The duration of follow-up observation was 3 months. Following the intra-articular injection of DW-166HC, the blood radioactivity was little changed from the baseline measurement and the accumulated radioactivity excreted in urine was minimal. Gamma scan study indicated that most of the injected radiochemical was localized within the injected joint cavity, and the extra-articular leakage was negligible at 24 h after the injection: brain, 0.3%; lung, 0.6%; abdomen, 0.7%; and pelvis, 0.8%. Major adverse events were transient post-injection knee joint pain and swelling. These results suggest that DW-166HC might be a safe agent for radiation synovectomy, particularly for the treatment of knee synovitis of RA, and further trials in a larger patient population are warranted to evaluate the therapeutic efficacy of DW-166HC. (orig.)

  18. Development of Holmium 166-chitosan complex as a radiopharmaceutical agent for liver cancer therapy

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    Ryu, Jei Man; Nam, Soon Chul; Park, Sun Joo; Moon, Eun Yi; Lee, Won Yong; Shin, Dong Hyuk; Cho, Eun Hee [Korea Atomic Energy Research Instisute, Taejon (Korea, Republic of)

    1997-09-01

    Effective therapeutic methods for cancer disease should be developed because the frequency of cancer disease is being increased rapidly. But there is no effective therapeutic method for treating these disease until now. The purpose of this research is to gain the clinical approval of Holmium{sup 166}-Chitosan complex as a radiopharmaceutical agent for liver cancer. We finished the preclinical test of Holmium{sup 166}-Chitosan complex and got the approval for clinical trial of this agent. 12 refs., 11 tabs., 9 figs. (author)

  19. Calcium phosphate holmium-166 ceramic to addition in bone cement: synthesis and characterization

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    Donanzam, Blanda A.; Campos, Tarcisio P.R., E-mail: campos@nuclear.ufmg.b [Universidade do Federal de Minas Gerais (DEN/UFMG), Belo Horizonte, MG (Brazil). Escola de Engenharia. Dept. de Engenharia Nuclear; Dalmazio, Ilza; Valente, Eduardo S., E-mail: id@cdtn.b, E-mail: valente@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2011-07-01

    Spine metastases are a common and painful complication of cancer. The treatment often consists of bone cement injection (vertebroplasty or kyphoplasty) within vertebral body for vertebrae stabilization, followed by external beam radiation therapy. Recently, researchers introduced the concept of radioactive bone cement for spine tumors therapy. Then, investigations about bioactive and radioactive materials became interesting. In this study, we present the synthesis of calcium phosphate incorporated holmium (CaP-Ho) via sol-gel technique, and its characterization by XRD, FT-IR, NA and SEM. Results showed a multiphasic bioceramic composed mainly of hydroxyapatite, {beta}-tricalcium phosphate, holmium phosphate and traces of calcium pyrophosphate. Furthermore, the nuclide Ho-166 was the major radioisotope produced. Despite that, the radioactive bioceramic CaP-{sup 166}Ho must be investigated in clinical trials to assure its efficacy and safety on spine tumors treatment (author)

  20. Holmium-166m: multi-gamma standard to determine the activity of radionuclides in semiconductor detectors

    International Nuclear Information System (INIS)

    The efficiency and calibration curves as function of gamma-ray energy for a germanium detector are usually established by using many standard gamma ray sources of radionuclides decaying with few gamma rays or radionuclides having complex decay scheme, as 152Eu or 133Ba. But these radionuclides cannot be used alone, because they have a few gamma lines with high intensity and these lines have a irregular distribution in the energy spectrum. 166mHo is found to be a convenient single source for such calibration, because it decays by β- with subsequent emission of about 40 strong and well distributed gamma lines between 80 and 1500 keV. Moreover, its long half - life (1200 years) and X-rays characteristics between 40 and 50 keV makes it a good standard for calibration of germanium detectors. However, it is necessary to know with accuracy and precision the gamma ray intensities of their main lines, due to the fact that literature has showed discrepant values. Then, a methodology to determine the emission probability of its main lines is proposed by means of combined use of gamma spectrometry and coincidence 4πβ -γ techniques. The experimental results show consistence to the others authors, with lower or compatible uncertainties. (author)

  1. Production of microspheres labeled with holmium-166 for liver cancer therapy: the preliminary experience at IPEN/CNEN-SP

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    Costa, Renata F.; Azevedo, Mariangela B.M.; Nascimento, Nanci; Sene, Frank F.; Martinelli, Jose R.; Osso Junior, Joao A., E-mail: renatafcosta@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    Microspheres labeled with therapeutic radionuclides for malignancies of liver are widely used in many countries. The internal radionuclide therapy uses a permanently implanted device, such as Therasphere{sup R} or SIR-Spheres{sup R}, or a biodegradable device that provides structural support for the radionuclide of choice and causes the tumor reduction. Three different types of material supports have been investigated, i.e., biodegradable polymer-based, glass-based and resin-based microspheres. Nowadays there is a project concerning the labeling of these 3 materials with {sup 166}Ho being developed at IPEN-CNEN/SP and coordinated by the Radiopharmacy Directory. {sup 166}Ho(t{sub 1/2}=26.8 h) is a beta minus emitter (E{sub max}=1.84 MeV), with right properties for radiotherapy and can be produced with the low power Brazilian Nuclear Reactor IEA-R1m. The aim of this work is to describe the stage of development of this project. The initial experience used resin-based microspheres, a cation exchange resin labeled with {sup 166}Ho, it showed the essential characteristics for liver therapy. Preliminary results of the preparation of glass-based microspheres labeled with {sup 165}Ho showed that 5% of Ho{sub 2}O{sub 3} was incorporated in an aluminosilicate glass, through the process of spheronization by flame, which produced spherical microspheres with 20-40mum particle size. The preparation of biodegradable material, polymer-based microspheres, is in its initial stage and the objective is to prepare and label with {sup 165}Ho different polymer-based microspheres. These combined efforts have been done to offer a national radiotherapeutic product for the the Brazilian nuclear medicine community at fair value and also to offer a viable possibility of treatment for patients affected by liver malignancies. (author)

  2. Multimodal imaging of holmium-loaded microsphere for internal Radiation therapy

    NARCIS (Netherlands)

    Seevinck, P.R.

    2009-01-01

    In this dissertation, the qualitative and quantitative multimodal imaging possibilities of holmium-166 loaded poly(L-lactic acid) microspheres (166Ho-PLLA MS) are explored and exploited to improve biodistribution assessment and dose calculations for planning, image-guidance and evaluation of hepatic

  3. Quantitative nuclear imaging for dosimetry in radioembolization

    NARCIS (Netherlands)

    Elschot, M.

    2013-01-01

    Intra-arterial microsphere radioembolization is an increasingly applied technique for treatment of unresectable liver tumors. During radioembolization, microspheres (diameter 30 μm) loaded with a high-energy beta-emitting radionuclide, such as yttrium-90 (Y-90) and holmium-166 (Ho-166), are instille

  4. Evaluation of the therapeutic effect of hydroxyapatite particles labeled with Ho sub 1 sub 6 sub 6 in rats with acute and chronic arthritis

    CERN Document Server

    Mendoza-Lopez, P

    2002-01-01

    with significantly statistical values (p<=0,01). This therapeutic effect was evident too when evaluating the measure of the articular perimeter in acute and chronic arthritis groups through the time with significantly statistical values (p<=0,01). In conclusion the hydroxyapatite particles labeled with Holmium-166 are biologically stable in vivo and have a therapeutic effect in the treatment of acute and chronic arthritis in rats. The therapeutic effect of an intraarticular injection of hydroxyapatite particles labeled with Holmium-166 ( Ho sub 1 sub 6 sub 6 HA) was evaluated. For this evaluation 72 antigen-induced arthritis rats; the arthritis was induced by an intraarticular injection of a suspension of ovoalbumin and Freund's adjuvant complete. The 72 rats were divided in three groups: control group, acute arthritis group and chronic arthritis group. The evaluation of the therapeutic effect was achieved by the measuring of the perimeter of the arthritic knee joint in different days after the intraart...

  5. Radiolanthanides in therapeutic nuclear oncology

    International Nuclear Information System (INIS)

    Radiolanthanides such as Holmium-166 (T1/2 26.8h), Samarium-153 (T1/2 46.3h) and Lutetium-177 (T1/2 6.7 days) all have beta emissions suitable for radiopharmaceutical therapy, bone marrow ablation and for pain palliation of skeletal metastases. They also emit gamma photons of energies which permit quantitative imaging on conventional gamma cameras which facilitates calculation of dosimetry in individual patients. The range of half-lives has the potential to match the irradiation of tumour cells to the residence time of the radiopharmaceutical thus minimising radiotoxicity to normal tissues. Relative ease and low cost of production of these radiolanthanides in rectors such as HIFAR at ANSTO render radiolanthanides a practical option for radiopharmaceutical treatment of cancer for patients in whom conventional therapy has failed. Radioimmunotherapy of cancer using various monoclonal antibodies targeted to specific tumor-cell antigens has been performed with Samarium-153, Holmium-166 and Lutetium-177-labelled antibodies in human tumor xenographs in nude mice and in clinical trials. The development of a large animal model of human cancer will be described, in particular in relation to improving the accuracy of prediction of dosimetry and preclinical evaluation of efficacy and toxicity of radiolanthanides in therapeutic nuclear oncology

  6. Separation device of radio lanthanides (DISER)

    International Nuclear Information System (INIS)

    At the present time the cancer is one of the main causes of mortality in our country, therefore, its prevention, diagnostic and treatment is of vital importance for those health systems. The treatment of the cancer and other illnesses, starting from monoclonal antibodies, peptides, macro aggregates or marked aminoacids with beta particles emitting radioisotopes, it is an extremely promising field. The radioactive lanthanides: Promethium 149, Terbium 161, Holmium 166 and Lutetium 177 are beta emitting (β), which possess nuclear and chemical properties that have shown their feasibility like radioisotopes of radiotherapeutic use. However, these radioisotopes are not commercially available; to this respect, the Radioactive Materials Research Laboratory (LIMR) of the National Institute of Nuclear Research (ININ), it has developed the methodology of production of these radioisotopes and based on these works, there is designed, built and mounted the Radio lanthanides Separation Device (DISER) able to carry out the radioisotopes production in a routine way. This device is content in a cell that has an auxiliary air service, an extraction system and it is protected with a lead armor-plating of 10 cm. The DISER it is manual and easy of managing. The main function of this equipment is the radio lanthanides separation starting from the extractive chromatography by means of packed columns with a commercial resin (LnSPS) and recovered in the superior and inferior part by fiber glass. The DISER is composed by a main carrousel where the separation columns and the elution recipients are mounted. Also counts with an opening system of irradiation vials, port samples for columns and glass material. The present work presents a detailed description of the DISER, as well as its handling that allows to produce the radioisotopes Promethium-149, Terbium-161, Holmium-166 and Lutetium-177 starting from the separation of its parent elements Neodymium-149, Gadolinium-161, Dysprosium-166 and

  7. Separation device of radio lanthanides (DISER); Dispositivo de separacion de radiolantanidos (DISER)

    Energy Technology Data Exchange (ETDEWEB)

    Vera T, A.L. [FES-Zaragoza, UNAM, 09000 Mexico D.F. (Mexico); Monroy G, F.; Vazquez M, J.C.; Jimenez B, F. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)]. e-mail: veratrevino@hotmail.com

    2008-07-01

    At the present time the cancer is one of the main causes of mortality in our country, therefore, its prevention, diagnostic and treatment is of vital importance for those health systems. The treatment of the cancer and other illnesses, starting from monoclonal antibodies, peptides, macro aggregates or marked aminoacids with beta particles emitting radioisotopes, it is an extremely promising field. The radioactive lanthanides: Promethium 149, Terbium 161, Holmium 166 and Lutetium 177 are beta emitting ({beta}), which possess nuclear and chemical properties that have shown their feasibility like radioisotopes of radiotherapeutic use. However, these radioisotopes are not commercially available; to this respect, the Radioactive Materials Research Laboratory (LIMR) of the National Institute of Nuclear Research (ININ), it has developed the methodology of production of these radioisotopes and based on these works, there is designed, built and mounted the Radio lanthanides Separation Device (DISER) able to carry out the radioisotopes production in a routine way. This device is content in a cell that has an auxiliary air service, an extraction system and it is protected with a lead armor-plating of 10 cm. The DISER it is manual and easy of managing. The main function of this equipment is the radio lanthanides separation starting from the extractive chromatography by means of packed columns with a commercial resin (LnSPS) and recovered in the superior and inferior part by fiber glass. The DISER is composed by a main carrousel where the separation columns and the elution recipients are mounted. Also counts with an opening system of irradiation vials, port samples for columns and glass material. The present work presents a detailed description of the DISER, as well as its handling that allows to produce the radioisotopes Promethium-149, Terbium-161, Holmium-166 and Lutetium-177 starting from the separation of its parent elements Neodymium-149, Gadolinium-161, Dysprosium-166

  8. Production of Medical Radioisotopes in the ORNL High Flux Isotope Reactor (HFIR) for Cancer Treatment and Arterial Restenosis Therapy after PTCA

    Science.gov (United States)

    Knapp, F. F. Jr.; Beets, A. L.; Mirzadeh, S.; Alexander, C. W.; Hobbs, R. L.

    1998-06-01

    The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory (ORNL) represents an important resource for the production of a wide variety of medical radioisotopes. In addition to serving as a key production site for californium-252 and other transuranic elements, important examples of therapeutic radioisotopes which are currently routinely produced in the HFIR for distribution include dysprosium-166 (parent of holmium-166), rhenium-186, tin-117m and tungsten-188 (parent of rhenium-188). The nine hydraulic tube (HT) positions in the central high flux region permit the insertion and removal of targets at any time during the operating cycle and have traditionally represented a major site for production of medical radioisotopes. To increase the irradiation capabilities of the HFIR, special target holders have recently been designed and fabricated which will be installed in the six Peripheral Target Positions (PTP), which are also located in the high flux region. These positions are only accessible during reactor refueling and will be used for long-term irradiations, such as required for the production of tin-117m and tungsten-188. Each of the PTP tubes will be capable of housing a maximum of eight HT targets, thus increasing the total maximum number of HT targets from the current nine, to a total of 57. In this paper the therapeutic use of reactor-produced radioisotopes for bone pain palliation and vascular brachytherapy and the therapeutic medical radioisotope production capabilities of the ORNL HFIR are briefly discussed.

  9. Production and characterization of 166Ho polylactic acid microspheres.

    Science.gov (United States)

    Yavari, Kamal; Yeganeh, Ehsan; Abolghasemi, Hossein

    2016-01-01

    Microsphere and particle technology with selective transport of radiation represents a new generation of therapeutics. Poly-L-lactic acid (PLLA) microspheres loaded with holmium-166 acetylacetonate ((166)Ho-PLLA-MS) are novel microdevices. In this research, (165)HoAcAc-PLLA microparticles were prepared by the solvent evaporation technique. Microspheres were irradiated at Tehran Research Reactor. The diameter and surface morphologies were characterized by particle sizer and scanning electron microscopy before and after irradiation. The complex stability, radiochemical purity, and in vivo biodistribiotion were checked in the final solution up to 3 days. In this study, (166)Ho-PLLA spherical particles with a smooth surface and diameter of 20-40 µm were obtained, which were stable in vitro and in vivo studies. Neutron irradiation did not damage the particles. The ease with which the PLLA spheres could be made in the optimal size range for later irradiation and their ability to retain the (166)Ho provided good evidence for their potential use in radioembolization.

  10. Pharmacokinetics of Genetically Engineered Antibody Forms Using Positron Emission Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Steven M. Larson, M.D. Nai-Kong Cheung, M.D., Ph.D.

    2004-08-31

    In the last grant period we have focused on multi-step targeting methodologies (MST), as a method for delivery of high dose to the tumor, with low dose to the bone marrow. We have explored uptake in colorectal, pancreatic and prostate cancer, using an special preparation, developed in collaboration with NeoRex A high tumor/bone marrow ratio is clearly achieved with MST, but with a cost, namely the higher dose to normal kidney. For this reason, we have in particular, (a) looked dosimetry for both tumor and normal organ, and especially renal dosimetry, which appears to be the target organ, for Y-90. (b) In parallel with this we have explored the dosimetry of very high dose rate radionuclides, including Holmium-166. (c) In addition, with NaiKong Cheung, we have developed a new MST construct based on the anti-GD2 targeting 5F11; (d) we have successfully completed development of s-factor tables for mice. In summary, renal dosimetry is dominated by about 4-5% of the injected dose being held long-term in the renal cortex, probably in the proximal tubule, due to the universal uptake of small proteins. This appears to be a function of a biotynlated protein binding of the strept-avidin construct, to HSP70. This cortical uptake has caused us to reconsider renal dosimetry as a whole, with the smaller mass of the cortex, rather than the whole kidney, as the target organ. These insights into dosimetry will be of great importance as MST, becomes more common in clinical practice.

  11. Radionuclide liver cancer therapies: from concept to current clinical status.

    Science.gov (United States)

    Vente, Maarten A D; Hobbelink, Monique G G; van Het Schip, Alfred D; Zonnenberg, Bernard A; Nijsen, Johannes F W

    2007-07-01

    Primary and secondary liver cancer have longtime been characterized by an overall poor prognosis since the majority of patients are not candidates for surgical resection with curative intent, systemic chemotherapy alone has rarely resulted in long-term survival, and the role of conventional external beam radiation therapy has traditionally been limited due to the relative sensitivity of the liver parenchyma to radiation. Therefore, a host of new treatment options have been developed and clinically introduced, including radioembolization techniques, which are the main topic of this paper. In these locoregional treatments liver malignancies are passively targeted because, unlike the normal liver, the blood supply of intrahepatic tumors is almost uniquely derived from the hepatic artery. These internal radiation techniques consist of injecting either yttrium-90 ((90)Y) microspheres, or iodine-131 ((131)I) or rhenium-188 ((188)Re) labeled lipiodol into the hepatic artery. Radioactive lipiodol is used exclusively for treatment of primary liver cancer, whereas (90)Y microsphere therapy is applied for treatment of both primary and metastatic liver cancers. Favorable clinical results have been achieved, particularly when (90)Y microspheres were used in conjunction with systemic chemotherapy. The main advantages of radiolabeled lipiodol treatment are that it is relatively inexpensive (especially (188)Re-HDD-lipiodol) and that the administration procedure is somewhat less complex than that of the microspheres. Holmium-166 ((166)Ho) loaded poly(L-lactic acid) microspheres have also been developed and are about to be clinically introduced. Since (166)Ho is a combined beta-gamma emitter and highly paramagnetic as well, it allows for both (quantitative) scintigraphic and magnetic resonance imaging. PMID:17630919

  12. Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization.

    Directory of Open Access Journals (Sweden)

    Mattijs Elschot

    Full Text Available BACKGROUND: Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE. In yttrium-90 (90Y RE, scintigraphic images of technetium-99m (99mTc are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared. METHODOLOGY/PRINCIPAL FINDINGS: Phantom experiments were performed in line with NEMA guidelines to assess the spatial resolution, sensitivity, count rate linearity, and contrast recovery of 99mTc, 90Y and 166Ho. In addition, Monte Carlo simulations were performed to obtain detailed information about the history of detected photons. The results showed that the use of a broad energy window and the high-energy collimator gave optimal combination of sensitivity, spatial resolution, and primary photon fraction for 90Y Bremsstrahlung imaging, although differences with the medium-energy collimator were small. For 166Ho, the high-energy collimator also slightly outperformed the medium-energy collimator. In comparison with 99mTc, the image quality of both 90Y and 166Ho is degraded by a lower spatial resolution, a lower sensitivity, and larger scatter and collimator penetration fractions. CONCLUSIONS/SIGNIFICANCE: The quantitative evaluation of the scintillation camera characteristics presented in this study helps to optimize acquisition parameters and supports future analysis of clinical comparisons between RE studies.

  13. [166Dy]Dy/166Ho hydroxide macroaggregates: an in vivo generator system for radiation synovectomy.

    Science.gov (United States)

    Ferro-Flores, G; Hernández-Oviedo, O; Arteaga de Murphy, C; Tendilla, J I; Monroy-Guzmán, F; Pedraza-López, M; Aldama-Alvarado, K

    2004-12-01

    Radiation synovectomy is an effective treatment in patients suffering from inflammatory-rheumatoid and degenerative joint diseases. The aim of this work was to examine the feasibility of preparing dysprosium-166 (166Dy)/holmium-166(166Ho) hydroxide macroaggregates ([166Dy]Dy/166Ho-HM) as an in vivo generator for radiation synovectomy evaluating whether the stability of 166Dy-HM and 166Ho-HM complexes is maintained when the daughter 166Ho is formed. The Monte Carlo (MCNP4B) theoretical depth dose profile for the in vivo [166Dy]Dy/166Ho generator system in a joint model was calculated and compared with that produced by 90Y, 153Sm and 166Ho. 166Dy was obtained by neutron irradiation of enriched 164Dy2O3 in a Triga Mark III reactor. Macroaggregates were prepared by reaction of [166Dy]DyCl3 with 0.5 M NaOH in an ultrasonic bath. [166Dy]Dy/166Ho-HM was obtained with radiochemical purity >99.5% and with the majority of particles in the 2-5 microm range. In vitro studies demonstrated that the radio-macroaggregates are stable in saline solution and human serum without a significant change in the particle size over 14 d, suggesting that no translocation of the daughter nucleus occurs subsequent to beta- decay of 166Dy. Biological studies in normal rats demonstrated high retention in the knee joint even 7 d after [166Dy]Dy/166Ho-HM administration. The Monte Carlo (MCNP4B) theoretical depth dose profiles in a joint model, showed that the in vivo [166Dy]Dy/166Ho generator system would produce 25% and 50% less radiation dose to the articular cartilage and bone surface, respectively, than that produced by 90Y or pure 166Ho in a treatment with the same therapeutic dose to the synovium surface. Despite that 153Sm showed the best depth dose profile sparing doses to healthy tissues, the use of 166Dy could provide the advantage of being applied in patients that cannot be reached within a few hours from a nuclear reactor and to produce less radiation exposure to the medical personnel

  14. Labeling of biotin with 166Dy/166Ho as a stable in vivo generator system

    International Nuclear Information System (INIS)

    Biotin (cis-tetrahydro-2-oxothieno[3,4-d]imidazoline-4-valeric acid) is a 244 Da vitamin found in low concentration in blood and tissue (vitamin H). The aim of this work was to synthesize 166Dy/166Ho-DTPA-bisBiotin to evaluate its potential as a new radiopharmaceutical for targeted radiotherapy. Dysprosium-166/ holmium-166 chloride was obtained by neutron irradiation of 20 mg of enriched Dy2O3 (164Dy, 99 %, from Oak Ridge NL) in a Triga Mark III reactor at a flux in the central thimble of 3.1013 n. cm-2 s-1 for 20 h. Following irradiation, the target was allowed to decay for 2 days, then 100 μL of 12 N chloride acid were added and stirred for 1 min. To this solution was added 500 μL of injectable water and the whole was also stirred for 2 min. The average radioactive concentration was 332 MBq/ml. The biotin used in this investigation was covalently conjugated to diethylenetriamine pentaacetic acid (DTPA) through the use of the cyclic anhydride and lysine conjugate to biotin (biocytin) to produce DTPA-α,ω-bis(biocytin amide)(DTPA-bisBiotin). Sterile and apyrogenic V-vial was prepared to contain 2.0 mg (1.9 x 10-3 mmol) of the DTPA-bisbiotin compound in 1.0 ml of 0.05 M bicarbonate buffer (pH 8.0) and then 20 μL of 166Dy2Cl3 solution were added to the preparation. Thin Layer Chromatography aluminum cellulose sheets were utilised as the stationary phase and a ternary mixture of methanol:water:ammonium hydroxide (20:40:2) as the mobile phase. 166Dy/166Ho-DTPA-bisBiotin travelled with the solvent front Rf 0.9-1.0 and the Dy+3/Ho+3 species remained at the origin (Rf = 0). The biological integrity of labelled biotin was achieved evaluating its avidity for avidin in an agarose column. Stability studies against dilution were carried out by diluting the radiocomplex solution with saline and with human serum at 310 K. After 10 min and 24 h the radiochemical purity of each 166Dy/166Ho complex solution was determined by TLC. The complex 166Dy/166Ho-DTPA-bisBiotin was

  15. Temperature and Stretching Effects on Complementarity Determining Regions (CDRs Conformation and Stability of Nimotuzumab F(ab-Fragment

    Directory of Open Access Journals (Sweden)

    T.S. Humani

    2015-04-01

    Full Text Available Nimotuzumab is a humanized monoclonal antibody (mAb, a potential anticancer against epidermal growth factor receptor (EGFRoverexpressed by glioma, head and neck, lung, ovarium, and colon cancers. The combination of its use with both external and internal beam radiotherapies showed improvement of the therapeutic effect. However, the high molecular weight slows its uptake on tumor cells. In a recent development, nimotuzumab has been fragmented and then labeled using diagnostic and therapeutic radionuclides, such as gallium-68, yttrium-90, lutetium-177, and holmium-166. In that preparation, nimotuzumab is often conditioned in various environments with variations of pH, temperature and the presence of other compounds. In this research, molecular dynamics (MD simulation have been carried out to study the CDRs conformational change of nimotuzumab due to the effect of temperature, and also steered molecular dynamics (SMD simulation to study the stability of nimotuzumab domain as a result of external forces. The simulations were performed using the Not Just Another Molecular Dynamics (NAMD program package and the analysis was performed with the Visual Molecular Dynamics (VMD program package. Based on the stability analysis of each residue on the heavy chain, the active site (CDR3 region that is at residues numbered 98 (Tryptophan and 99 (Phenylalanine has the highest conformational changes. On the light chain, the change occurs at residues numbered 1 (Aspartat, 127 (Serin, and 186 (Tyrosine; and that none of that residues is part of active site or CDRs region of the light chain. The SMD simulation was carried out by fixing the N-terminal end of the heavy chain and applying external forces to the C-terminal end. The pulling was set at a constant velocity of 0.5 Å/ps. The force peak arising at the beginning of the unfolding process is 1226 pN. This force was allegedly caused by the rupture of hydrogen bonds between the heavy chain residue VAL211 (Valine

  16. Preparation of 166 Dy/166 Ho-Macro aggregates as an In vivo generator system for the treatment of arthrophaties

    International Nuclear Information System (INIS)

    The present work reports the obtention of macro aggregates of hydroxides of Dysprosium-166/Holmium-166 (166 Dy/166 Ho-MH), as a generator system in vivo to be used in the treatment of arthritis rheumatoid. The 166 Dy was obtained by neutron irradiation of 166 DyO3 (enriched to 98.45%) by 20 h in the TRIGA Mark III Reactor and 50 h of decay, to the oxide of 166 Dy/166 Ho formed, it was added HCl 0.12 N to obtain a final volume of 3.5 ml of solution of 166 Dy/166 Ho chloride. The solution of 166DyCl3 solution was obtained with an activity of 3.502 mCi (129 MBq), appropriate for the preparation of the radiopharmaceutical 166 Dy/166 Ho-MH. The separation of the 166 Dy from the 166 Ho, was carried out by chromatography in an cation exchange column, gaining an appropriate separation, obtaining a 166 Dy with a radionuclide purity greater than 90%. The 166 Dy/166 Ho-MH were prepared by addition to the solution of 166 DyCI3 NaOH 0.5 N low ultrasonic bath with later centrifugation, decanted and resuspension in saline solution, obtaining a radiopharmaceutical with a generator system 166 Dy/ 166 Ho with particles of size average of 3 μm, in form of 166 Dy / 166 Ho-MH. Under these conditions, it was obtained a radiochemical yield greater than 99%. The microscopic analysis and of filtration showed that the formulation doesn't present particles smaller than to 1 μm, neither greater to 50 μm, which will allow, the quick phagocytosis for the synoviocytes of the synovial membrane, and by consequence, an homogeneous distribution of the radiation dose could exist. The sedimentation velocity for the formulated suspension is of 0.04 cm/min that it will allow the administration of homogeneous activities of the radiopharmaceutical, to the no deposit in the injection devices. The studies of stability in vitro indicate us that inside the articulation, the particles won't probably reduce its size neither their radiochemical purity, for that the flight extra articular will be smaller that

  17. Preparation of {sup 166} Dy/{sup 166} Ho-Macro aggregates as an In vivo generator system for the treatment of arthrophaties; Preparacion de {sup 166} Dy/{sup 166} Ho-Macro agregados como un sistema de generador In vivo para el tratamiento de artropatias

    Energy Technology Data Exchange (ETDEWEB)

    Aldama A, T.K

    2003-07-01

    The present work reports the obtention of macro aggregates of hydroxides of Dysprosium-166/Holmium-166 ({sup 166} Dy/{sup 166} Ho-MH), as a generator system in vivo to be used in the treatment of arthritis rheumatoid. The {sup 166} Dy was obtained by neutron irradiation of {sup 166} DyO{sub 3} (enriched to 98.45%) by 20 h in the TRIGA Mark III Reactor and 50 h of decay, to the oxide of {sup 166} Dy/{sup 166} Ho formed, it was added HCl 0.12 N to obtain a final volume of 3.5 ml of solution of {sup 166} Dy/{sup 166} Ho chloride. The solution of {sup 166D}yCl{sub 3} solution was obtained with an activity of 3.502 mCi (129 MBq), appropriate for the preparation of the radiopharmaceutical {sup 166} Dy/{sup 166} Ho-MH. The separation of the {sup 166} Dy from the {sup 166} Ho, was carried out by chromatography in an cation exchange column, gaining an appropriate separation, obtaining a {sup 166} Dy with a radionuclide purity greater than 90%. The {sup 166} Dy/{sup 166} Ho-MH were prepared by addition to the solution of {sup 166} DyCI{sub 3} NaOH 0.5 N low ultrasonic bath with later centrifugation, decanted and resuspension in saline solution, obtaining a radiopharmaceutical with a generator system {sup 166} Dy/ {sup 166} Ho with particles of size average of 3 {mu}m, in form of {sup 166} Dy / {sup 166} Ho-MH. Under these conditions, it was obtained a radiochemical yield greater than 99%. The microscopic analysis and of filtration showed that the formulation doesn't present particles smaller than to 1 {mu}m, neither greater to 50 {mu}m, which will allow, the quick phagocytosis for the synoviocytes of the synovial membrane, and by consequence, an homogeneous distribution of the radiation dose could exist. The sedimentation velocity for the formulated suspension is of 0.04 cm/min that it will allow the administration of homogeneous activities of the radiopharmaceutical, to the no deposit in the injection devices. The studies of stability in vitro indicate us that inside

  18. Preparation of 166Ho-macroaggregates and 166Ho-chitosan for the endoradiotherapy

    International Nuclear Information System (INIS)

    Aim: The purpose of this study was focused on the preparation Holmium-166 based agents for the radionuclide synovectomy (166Ho-macroaggregates) and for the hepatic cancer therapy (66Ho-chitosan complex). Radionuclide synovectomy (radiation synovectomy) is an alternative method, that cures patients with rheumatoid arthritis diseases without surgery. During treatment, the suspension of the radioactive particles is administrated via intra-articular injection into the target joint to destroy inflamed synovium. In case of hepatic tumour therapy treatment, 166Ho-chitosan complex can be administrated either directly into the tumour, or via catheter into hepatic artery. Materials and Methods: Isotope 166Ho (E beta max = 1.84 MeV, half life = 26,8 hr) was prepared by the 165Ho(n, gamma)166Ho reaction at the neutron flux approximately 1014 cm-2s-1. The Ho-macroaggregates (Ho-MA) were prepared by reacting the aqueous solution of Ho(NO3)3 with sodium borohydride solution in 0.2 M NaOH. The particle size distribution of the prepared Ho-MA was determined by the Laser Particle Size Analyser. Quality of the prepared Ho-MA particles was investigated by the electron microscope. The in-vitro stability studies were carried out by incubation 166Ho-MA in 6 ml 0.9 % NaCl solution. The in-vivo stability studies of the 166Ho-B-MA were done at 24 hours after administration of 166Ho-MA into the knee joint of the rat (Wistar, 190-200g). The 166Ho-chitosan complex was prepared by reacting of Ho(NO3)3.5H2O with chitosan, which M.W. was from 150000 to 600000. The time dependence of 166Ho-Chitosan viscosity was measured using Rheometer RC20-CPS (Rheotec). Radiochemical purity of 166Ho-Chitosan complex was measured by radio TLC method. Results: Studies carried out with 166Ho-MA showed very good in-vitro stability prepared particles. The radioactivity leakage percentage was less then 5 % within approximately 190 hours of incubation. In-vivo studies showed very high retention of 166Ho-MA in the