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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. MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation

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    Maat, Gerrit H. van de; Seevinck, Peter R.; Leeuw, Hendrik de; Viergever, Max A. [University Medical Center Utrecht, Image Sciences Institute, Q S.459, PO Box 85500, Utrecht (Netherlands); Elschot, Mattijs; Smits, Maarten L.J.; Schip, Alfred D. van het; Vente, Maarten A.D.; Zonnenberg, Bernard A.; Jong, Hugo W.A.M. de; Lam, Marnix G.E.H.; Bosch, Maurice A.A.J. van den; Nijsen, Johannes F.W.; Bakker, Chris J.G. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands)

    2013-03-15

    To demonstrate the feasibility of MRI-based assessment of the intrahepatic Ho-PLLA-MS biodistribution after radioembolisation in order to estimate the absorbed radiation dose. Fifteen patients were treated with holmium-166 ({sup 166}Ho) poly(L-lactic acid)-loaded microspheres (Ho-PLLA-MS, mean 484 mg; range 408-593 mg) in a phase I study. Multi-echo gradient-echo MR images were acquired from which R{sub 2} {sup *} maps were constructed. The amount of Ho-PLLA-MS in the liver was determined by using the relaxivity r{sub 2} {sup *} of the Ho-PLLA-MS and compared with the administered amount. Quantitative single photon emission computed tomography (SPECT) was used for comparison with MRI regarding the whole liver absorbed radiation dose. R{sub 2} {sup *} maps visualised the deposition of Ho-PLLA-MS with great detail. The mean total amount of Ho-PLLA-MS detected in the liver based on MRI was 431 mg (range 236-666 mg) or 89 {+-} 19 % of the delivered amount (correlation coefficient r = 0.7; P < 0.01). A good correlation was found between the whole liver mean absorbed radiation dose as assessed by MRI and SPECT (correlation coefficient r = 0.927; P < 0.001). MRI-based dosimetry for holmium-166 radioembolisation is feasible. Biodistribution is visualised with great detail and quantitative measurements are possible. (orig.)

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

    NARCIS (Netherlands)

    Smits, Maarten L J; Nijsen, Johannes F W; van den Bosch, Maurice A A J; Lam, Marnix G E H; Vente, Maarten A D; Huijbregts, Julia E; van het Schip, Alfred D; Elschot, Mattijs; Bult, Wouter; de Jong, Hugo W A M; Meulenhoff, Pieter C W; Zonnenberg, Bernard A

    2010-01-01

    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 alt

  8. Intratumoral administration of Holmium-166 Acetylacetonate Microspheres: antitumor efficacy and feasibility of multimodality imaging in renal cancer

    NARCIS (Netherlands)

    Bult, W.; Kroeze, S.G.C.; Elschot, M.; Seevinck, P.R.; Beekman, F.J.; De Jong, H.W.A.M.; Uges, D.R.A.; Kosterink, J.G.W.; Luijten, P.R.; Hennink, W.E.; et al.

    2013-01-01

    The increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of holmium-166 microsp

  9. 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.

  10. 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.)

  11. 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.)

  12. Intratumoral administration of holmium-166 acetylacetonate microspheres: antitumor efficacy and feasibility of multimodality imaging in renal cancer.

    Directory of Open Access Journals (Sweden)

    Wouter Bult

    Full Text Available PURPOSE: The increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of holmium-166 microspheres ((166HoAcAcMS. This new technique locally ablates renal tumors through high-energy beta particles, while the gamma rays allow for nuclear imaging and the paramagnetism of holmium allows for MRI. METHODS: (166HoAcAcMS were administered intratumorally in orthotopic renal tumors (Balb/C mice. Post administration CT, SPECT and MRI was performed. At several time points (2 h, 1, 2, 3, 7 and 14 days after MS administration, tumors were measured and histologically analyzed. Holmium accumulation in organs was measured using inductively coupled plasma mass spectrometry. RESULTS: (166HoAcAcMS were successfully administered to tumor bearing mice. A striking near-complete tumor-control was observed in (166HoAcAcMS treated mice (0.10±0.01 cm(3 vs. 4.15±0.3 cm(3 for control tumors. Focal necrosis and inflammation was present from 24 h following treatment. Renal parenchyma outside the radiated region showed no histological alterations. Post administration CT, MRI and SPECT imaging revealed clear deposits of (166HoAcAcMS in the kidney. CONCLUSIONS: Intratumorally administered (166HoAcAcMS has great potential as a new local treatment of renal tumors for surgically unfit patients. In addition to strong cancer control, it provides powerful multimodality imaging opportunities.

  13. 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

  14. 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

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    Lee, Sang Hoon; Suh, Jin Suck; Kim, Ho Seok; Lee, Jong Doo; Song, Jung Sik; Lee, Soo Kon [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2003-09-01

    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.

  15. Polymeric microspheres for radionuclide synovectomy containing neutron-activated holmium-166.

    Science.gov (United States)

    Mumper, R J; Mills, B J; Ryo, U Y; Jay, M

    1992-03-01

    Poly-L-lactic acid (PLA) microspheres containing neutron-activated 166Ho were investigated as potential agents for radionuclide synovectomy. Stable 165Ho, complexed to acetylacetone (AcAc), was incorporated into PLA spheres by the solvent evaporation technique. Spheres prepared with the optimal mean particle size of 7.2 microns (range 2-13 microns) containing 25.4% 165Ho-AcAc (9.1% 165Ho) were irradiated in a high neutron flux to produce 31.1-36.0 mCi 166Ho. In vitro human plasma studies showed that the irradiated spheres retained 99.0 +/- 0.01% of the 166Ho at 314 hr. In-vivo retention studies were conducted by administering irradiated PLA spheres with 257-591 microCi 166Ho into the joint space of normal rabbits (n = 6). Biodistribution analysis and gamma camera analysis showed 166Ho retention in the joint space after 120 hr of 97.7% +/- 0.8% and 98.2% +/- 2.4%, respectively, with no uptake by the lymph nodes. The ease with which the PLA spheres can be made in the optimal size range for later irradiation and their ability to retain the 166Ho make them attractive agents for radionuclide synovectomy.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  19. Holmium radioembolization : Efficacy and safety

    NARCIS (Netherlands)

    Prince, J.F.

    2016-01-01

    This thesis describes the application of holmium-166 (166Ho) microspheres for radioembolization of hepatic malignancies. In radioembolization, a scout dose of technetium-99m macroaggregated albumin (99mTc-MAA) is injected in the hepatic artery first, as a scout dose, to screen for any of two contrai

  20. 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

  1. 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...

  2. Quantitative nuclear imaging for dosimetry in radioembolization

    OpenAIRE

    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 instilled in the hepatic artery via a catheter. The majority of microspheres will accumulate in and around the liver tumors, because these are almost exclusively perfused by arterial blood, whereas the hea...

  3. Quantitative Evaluation of Scintillation Camera Imaging Characteristics of Isotopes Used in Liver Radioembolization

    OpenAIRE

    Mattijs Elschot; Johannes Franciscus Wilhelmus Nijsen; Alida Johanna Dam; Hugo Wilhelmus Antonius Maria de Jong

    2011-01-01

    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 compa...

  4. 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

  5. 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.

  6. Production of medical radioisotopes in the ORNL High Flux Isotope Reactor (HFIR) for cancer treatment and arterial restenosis therapy after PTCA

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. 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.

  8. Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer.

    Science.gov (United States)

    Munaweera, Imalka; Shi, Yi; Koneru, Bhuvaneswari; Saez, Ruben; Aliev, Ali; Di Pasqua, Anthony J; Balkus, Kenneth J

    2015-10-05

    Lung cancer is the leading cause of cancer-related death in the United States and approximately 85% of all lung cancers are classified as nonsmall cell (NSCLC). We here use an innovative approach that may ultimately allow for the clinician to target tumors and aggressively reduce tumor burden in patients with NSCLC. In this study, a platinum (Pt)-based chemotherapeutic (cisplatin, carboplatin, or oxaliplatin) and holmium-165 (Ho), which can be neutron-activated to produce the holmium-166 radionuclide, have been incorporated together in a garnet magnetic nanoparticle (HoIG-Pt) for selective delivery to tumors using an external magnet. The synthesized magnetic HoIG nanoparticles were characterized using PXRD, TEM, ICP-MS, and neutron-activation. Platinum(II) drugs were incorporated onto HoIG, and these were characterized using FTIR, EDX, ICP-MS, and zeta potential measurements, and in vitro and in vivo studies were performed using a HoIG-platinum system. Results indicate that neutron-activated (166)HoIG-cisplatin is more toxic toward NSCLC A549 cells than is blank (166)HoIG and free cisplatin, and that when an external magnetic field is applied in vivo, higher tumor to liver ratios of Ho are observed than when no magnet is applied, suggesting that magnetic targeting is achieved using this system. Furthermore, an efficacy study demonstrated the inhibition of tumor growth by chemoradiotherapeutic magnetic nanoparticles, compared to no treatment controls.

  9. 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.

  10. Production of medical radioisotopes in the ORNL high flux isotope reactor (HFIR) for cancer treatment and arterial restenosis therapy after PICA

    Science.gov (United States)

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

    1999-01-01

    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. First beginning operation in 1965, the high thermal neutron flux (2.5×1015 neutrons/cm2/sec at 85 MW) and versatile target irradiation and handling facilities provide the opportunity for production of a wide variety of neutron-rich medical radioisotopes of current interest for therapy. 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-117 m 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 (22-24 days) 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-117 m 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.

  11. 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.

  12. 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

  13. 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