WorldWideScience

Sample records for cancerhapatocellular carcinomeby holmium-166

  1. Preparation of Holmium-166 Labelled Macroaggregates for radionuclide synovectomy

    Czech Academy of Sciences Publication Activity Database

    Kropáček, Martin; Melichar, František; Eigner-Henke, Kateřina; Konopková, M.

    2003-01-01

    Roč. 6, č. 1 (2003), s. 1-4. ISSN 1506-9680 Grant ostatní: GA MZd(CZ) NM6828 Institutional research plan: CEZ:AV0Z1048901 Keywords : Holmium -166 * Macroaggregate * Radionuclide Synovectomy Subject RIV: CH - Nuclear ; Quantum Chemistry

  2. Ocular brachytherapy with a holmium-166 irradiator device

    International Nuclear Information System (INIS)

    The ocular brachytherapy is a method that allows controlling ocular tumors. However, the irradiation of the ocular area in high doses can bring damages mainly to the surrounding healthy tissue, such as lens, retina and bone tissue of the orbital area in growth phase. Brachytherapy in comparison to teletherapy allows a large reduction of the absorbed doses in the adjacent tissues avoiding deleterious effects. Various types of radionuclides can be applied to ocular brachytherapy. Those radionuclides shall be encapsulated and placed juxtaposed to the sclera, back to the tumor. Herein, a new device was developed to encapsulate the radioactive material. It can easily place back of the eyeball. A computational model of the ocular area was developed in order to simulate the spatial dose distribution promoted by the holmium-166 nuclide distributed inside the irradiator device. The simulations addressed a device placed on the surface of the sclera, rotated 90 deg taken at the normal axis forward to the lens. The simulation was carried on the code Monte Carlo MCNP5. The computational simulation generates the spatial dose distribution in the treated volume. All continuous beta and the discrete gamma and X-ray spectra emitted by the holmium-166 were incorporated on simulations. The results allow comparing the space dose distribution to other types of sources used for the same end. The sclera absorbed dose, the maximum apical tumor dose, as well as on the tumor base were investigated. Indeed, the tumor thickness defines the conditions of irradiation. The holmium-166 dose distribution provides a tool to propose a better and optimized protocol for ocular brachytherapy. (author)

  3. Automated production of no carrier added Holmium-166

    International Nuclear Information System (INIS)

    Holmium-166 (166Ho) is used in radiotherapeutic applications such as radio-immunospecific pharmaceuticals, bone marrow ablation and radiation synovectomy and can be produced with moderate specific activity by the 165Ho[n,γ166Ho reaction. Higher specific activity carrier-free 166Ho can be obtained from the decay of dysprosium-166 (166Dy), produced by the double neutron capture reaction 164Dy[n.γ]165Dy[n,γ]166Dy. 166Ho can be separated from 166Dy by reverse phase ion exchange chromatography in high radionuclidic purity. An automated system has been developed to process the irradiated dysprosium oxide (Dy2O3) targets, carry out HPLC separation and deliver 166Ho in a form suitable for radiolabelling proteins and pharmaceuticals. (author)

  4. Holmium-166-chico intracavitary radiation therapy for cystic brain tumors

    International Nuclear Information System (INIS)

    Holmium-166-chitosan complex (Ho-166-chico) is injected into the unresectable seven cystic brain tumors (2 cases of metastatic brain tumors from lung cancer, 1 case of recurrent trigeminal neurinoma, 3 cases of recurrent low grade cystic astrocytomas, and 1 case of craniopharyngioma). The Ommaya reservoir was installed stereotactically. The cyst volume and wall thickness were measured by MRI before Ho-166-chico injection. The thickness of the cyst wall is up to 4 mm. Ho-166-chico (555-740 MBq) injected into the cyst to result in 25 Gy of dose to a cyst wall at a depth of 4 mm. Dose to the cyst wall was estimated by Monte Carlo simulation using the EGS4 code. All Ho-166-chico injected was assumed to be uniformly distributed in the spherical cyst. After Ho-166-chico injection, the distribution of isotopes was monitored by gamma camera. Two injections were administrated in two cases, and one injection in all the others. The response was evaluated with MRI. Four of 7 cases were shrunk in size with thinning of the cyst wall, 2 of 7 cases showed growth arrest, and one case showed progression. Estimated surface dose of cyst wall was between 78 and 2566 Gy. No one showed systemic absorption of Ho-166-chico, and specific complication associated with isotope injection. Ho-166-chico intracavitary radiation therapy for cystic brain tumor may be safe, and reliable method and deserves further evaluation

  5. 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

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

    International Nuclear Information System (INIS)

    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 (166Ho) 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 166Ho 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 166Ho projection images and incorporated in a statistical reconstruction algorithm (SPECT-fMC). Photon scatter and attenuation for all photons sampled from the full 166Ho 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 (Aest) and estimated radiation absorbed doses was evaluated using clinical SPECT data of six 166Ho 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% (SPECT-ppMC+DSW) to 76%–103

  7. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  9. 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...

  10. Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model

    International Nuclear Information System (INIS)

    Bone-seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of samarium-153 and holmium-166 are receiving considerable attention for therapeutic treatment of bone metastases. In this study, using the baboon experimental model, multicompartmental analysis revealed that with regard to pharmacokinetics, biodistribution, and skeletal localisation, 166Ho-EDTMP was significantly inferior to 153Sm-EDTMP and 99mTc-MDP. A more suitable 166Ho-bone-seeking agent should thus be sought for closer similarity to 153Sm-EDTMP to exploit fully the therapeutic potential of its shorter half-life and more energetic beta radiation

  11. Histological changes in the normal tissues of rat after local application of the holmium-166 chitosan complex attached to biodegradable solide material

    International Nuclear Information System (INIS)

    The aim of this study was to find out a clinically appliable method to insert a biodegradable solid material containing holmium 166-chitosan complex into the surgical field, and to evaluate the histological changes in the normal tissues after irradiation from holmium 166 according to the dose, period and type of tissues

  12. 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 (...

  13. 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...

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

    International Nuclear Information System (INIS)

    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 (166Ho) 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 R2* maps were constructed. The amount of Ho-PLLA-MS in the liver was determined by using the relaxivity r2* 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. R2* 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.)

  15. 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

  16. 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

  17. Experimental radiation synovectomy in rabbit knee with holmium-166 ferric hydroxide macroaggregate

    International Nuclear Information System (INIS)

    Holmium-166 ferric hydroxide macroaggregate (Ho-166 FHMA) particles possess two important properties for radiosynovectomy; relatively short half-life of the radioisotope and appropriate carrier size. Both these minimize radioactive leakage from the treated joint. This study was conducted to assess the effects of Ho-166 FHMA on synovium and synovial fluid in rabbit knee joints. Whole-knee autoradiography was utilized to determine distribution of radioactivity after intra-articular Ho-166 FHMA injection. Intra-articular injection of Ho-166 FHMA resulted in focal acute radiation necrosis in synovial lining but no hyperplasia of synoviocytes. Later, subsynovial fibrosis became evident. White blood cell and total protein levels in the joint fluid were elevated because of intra-articular inflammation due to the acute effects of radiation. Whole knee autoradiograms showed uneven distribution of the radionuclide along the synovium and extraarticular leakage on the third day after treatment

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Effects of Intraluminal Irradiation with Holmium-166 for TIPS Stenosis: Experimental Study in a Swine Model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Seon; Oh, Joo Hyeong; Kim, Deog Yoon; Park, Yong Koo; Kim, Soo Joong [Kyung Hee University Medical Center, Seoul (Korea, Republic of); Park, Sang Joon [Kang Dong Sacred Heart Hospital, Hallym University, Seoul (Korea, Republic of)

    2007-04-15

    We wanted to evaluate the effectiveness of intraluminal irradiation with Holmium-166 ({sup 166}Ho) for reducing the pseudointimal hyperplasia (PIH) in the transjugular intrahepatic portosystemic shunt (TIPS) tract in a swine model. TIPS was performed in 12 domestic pigs, after the creation of portal hypertension by intraportal injection of a mixture of N-butyl-2- cyanoacrylate (NBCA) and lipiodol. Five pigs first underwent intraluminal irradiation (30 Gy) in the parenchymal tract with using a {sup 166}Ho solution-filled balloon catheter, and this was followed by the placement of a nitinol stent in the TIPS tract. For the seven control pigs, the balloon was filled with saline and contrast media mixture. Two weeks later, follow-up portography and histological analysis were performed. TIPS was successfully performed in all twelve pigs with achieving artificially induced portal hypertension. Portography performed two weeks after TIPS showed the patent tracts in the TIPS tracts that were irradiated with {sup 166}Ho (5/5, 100%), whereas either completely (5/6, 83.3%) or partially (1/6, 16.7%) occluded TIPS were seen in the seven pigs of the nonirradiated control group, except in one pig that experienced periprocedural death due to bleeding. Histological analysis showed a statistically significant difference for the maximal PIH (irradiated: 32.8%, nonirradiated: 76.0%, p < 0.001) between the two groups. Intraluminal irradiation with 30 Gy of {sup 166}Ho for TIPS significantly improved the TIPS patency in a swine model of portal hypertension during a 2- week period of follow-up.

  20. Prospective dosimetry of intra-hepatic arterial holmium-166 microsphere therapy of liver metastases

    International Nuclear Information System (INIS)

    Full text: Preliminary results of yttrium 90 microsphere radiation therapy of liver cancer have been promising in patients refractory to all other treatment, but dosimetry of this pure beta emitter cannot be determined accurately. Holmium-166 has a beta emission of comparable energy and range to that of 90Y with the advantage of a gamma photon of 80 keV (6%) that can be imaged. We have calibrated our SPET system for quantitative imaging of a tracer dose of 500 MBq 166Ho-microspheres given via infusaport or directly into the hepatic artery, which lodge in the liver vasculature to preferentially irradiate the tumour. Using CT co-registration to define tumour margins, regions of interest of 5 pixels are positioned over normal liver parenchyma in each SPET slice and the radiation absorbed dose in Gray estimated to determine the additional administered therapy activity of 166Ho that would result in a dose to normal liver dose of 25 Gy. In an ongoing phase I clinical trial, 10 patients have received administered activities up to a maximum of 4.5 GBq.m-2, which gave a predicted radiation absorbed dose to normal liver of 29.3 ± 3.5 Gy using our method of SPET dosimetry. Follow-up SPET imaging at 6 days showed that the actual therapy radiation absorbed dose to normal liver parenchyma was 25.2 ± 4.4 Gy. Tumour radiation absorbed dose in these patients was estimated at 96.6 ± 42.0 Gy

  1. Therapeutic application of new holmium-166 chitosan complex in malignant and benign diseases

    International Nuclear Information System (INIS)

    The new holmium-166 chitosan complex (166Ho-CHICO, DW-166HC) was prepared by reacting the aqueous acidic solution of chitosan with 166Ho(NO3)3 at room temperature with quantitative labelling yield. The progress of the reaction and labelling yield were determined by instant this layer chromatography using silicic acid impregnated glass fiber (ITLC-SA) and developing solvent of MeOH:H2O:HAC (49:49:2). The high labelling yield of more than 99% was obtained by reacting chitosan solution (35 mg/4 ml) with 166Ho(NO3)3 in which 7 mg of 165Ho+166Ho were contained as a maximum content. The labelling yield was highly dependent on the pH of the chitosan solution. The optimal labelling could be obtained at pH 2.5∼3.5 The characteristics of 166Ho-CHICO were similar to those of chitosan, which is biocompatible, biodegradable, non-toxic, soluble and viscous in acidic condition but geltatinuous at pH 6.0 and precipitating in alkaline conditions. 166Ho-CHICO can be easily prepared by reconstituting freeze-dried chitosan (kit A) with 166Ho(NO3)3 solution (kit B) just prior to use. After intrahepatic administration of 166Ho-CHICO to male rats, the radioactivity concentrations in blood were low and the cumulative urinary and fecal excretion over a period of 0 to 72 hours were 0.53% and 0.54%, respectively. the radioactivity concentration in tissues and the whole-body autoradiography images showed that most of the administered radioactivity was localized at the administered site, and only slight radioactivity was detected from the liver, spleen, lungs, and bones. An autoradiograph after intratumoral administration of 166Ho-CHICO showed that radioactivity was localized at the administered site of the lesion without distribution to other organs and tissues. A biodistribution study in normal rabbits with 166Ho-CHICO showed that most of the radioactivities were retained in the knee joint with negligible extra leakage at 72 hours after intra-articular administration to male rabbits

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    International Nuclear Information System (INIS)

    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 (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 (166HoMS group only) hematologically over a period of 1 month (165HoMS group) or over 1 or 2 months (166HoMS 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 166HoMS 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-166HoMS administration. In the other blood parameters, no abnormalities were observed. Nuclear scans were acquired from all animals from the 166HoMS group, and MRI scans were performed if available. In pigs from the 166HoMS group, atrophy of one or more liver lobes was frequently observed. The actual radioactivity distribution was assessed through ex vivo 166mHo measurements. It can be concluded that the toxicity profile of HoMS is low. In pigs, hepatic arterial embolization with 166HoMS 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.)

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

    International Nuclear Information System (INIS)

    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-μm 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 166Ho activity was detected in kidneys (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.)

  5. Brachytherapy using holmium-166 liquid balloon system for in-stent restenosis: 6 months clinical and angiographic follow-up

    International Nuclear Information System (INIS)

    In western country, 3 systems of brachytherapy using commercial radioactive source has been established. However, brachytherapy using holmium-166 liquid balloon system (HLBS) for the patient with stent restenosis has not been studied enough. 30 patients (male 23, mean age 58.9 7.7) were enrolled. Target dose was 15 Gy at 1 mm distance from the intimal surface. Clinical diagnoses of the study patients included stable angina 10 and unstable angina 20 patients. Target lesion included LAD 19, LCx 5 and RCA 6 arteries. Pre-brachytherapy treatment included cutting balloon angioplasty in 25, rotational atherectomy in 5 patients. Fractionation and stepping was done in 6 patients each. Follow-up angiography was done in 19 patients. Of them, 4 cases developed angiographic restenosis (21%) including 3 cases of total occlusion. 6 month MACE (major adverse cardiac event) occurred in 5 patients including one sudden cardiac death in a patient with 80 year-old, triple-vessel diseased patient. Vascular brachytherapy using HLBS is a safe and effective treatment modality for in-stent restenosis showing acceptable angiographic and clinical result

  6. Radiotherapeutic bandage based on electrospun polyacrylonitrile containing holmium-166 iron garnet nanoparticles for the treatment of skin cancer.

    Science.gov (United States)

    Munaweera, Imalka; Levesque-Bishop, Daniel; Shi, Yi; Di Pasqua, Anthony J; Balkus, Kenneth J

    2014-12-24

    Radiation therapy is used as a primary treatment for inoperable tumors and in patients that cannot or will not undergo surgery. Radioactive holmium-166 ((166)Ho) is a viable candidate for use against skin cancer. Nonradioactive holmium-165 ((165)Ho) iron garnet nanoparticles have been incorporated into a bandage, which, after neutron-activation to (166)Ho, can be applied to a tumor lesion. The (165)Ho iron garnet nanoparticles ((165)HoIG) were synthesized and introduced into polyacrylonitrile (PAN) polymer solutions. The polymer solutions were then electrospun to produce flexible nonwoven bandages, which are stable to neutron-activation. The fiber mats were characterized using scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis and inductively coupled plasma mass spectrometry. The bandages are stable after neutron-activation at a thermal neutron-flux of approximately 3.5 × 10(12) neutrons/cm(2)·s for at least 4 h and 100 °C. Different amounts of radioactivity can be produced by changing the amount of the (165)HoIG nanoparticles inside the bandage and the duration of neutron-activation, which is important for different stages of skin cancer. Furthermore, the radioactive bandage can be easily manipulated to irradiate only the tumor site by cutting the bandage into specific shapes and sizes that cover the tumor prior to neutron-activation. Thus, exposure of healthy cells to high energy β-particles can be avoided. Moreover, there is no leakage of radioactive material after neutron activation, which is critical for safe handling by healthcare professionals treating skin cancer patients. PMID:25396281

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

    Directory of Open Access Journals (Sweden)

    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

  8. 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

  9. 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.)

  10. Effects of β-radiation using a Holmium-166 coated balloon on neointimal hyperplasia in a porcine coronary stent restenosis model

    International Nuclear Information System (INIS)

    Brachytherapy is a promising method of preventing and treating coronary stent restenosis. The present study was designed to observe the therapeutic effects of a radioactive balloon loaded with Holmium-166 (166Ho) in a porcine coronary stent restenosis model. A radioisotope of 166Ho was coated onto the balloon surface using polyurethane (20 Gy at 0.5 mm depth). Stent overdilation injuries were induced in 2 coronary arteries in each pig (n=8). Four weeks after the injury, control balloon dilation was performed in one coronary artery (Group I) and radiation therapy using the 166Ho coated balloon in the other coronary artery (Group II) in each pig. Follow-up coronary angiography and histopathologic assessment were performed at 4 weeks after the radiation therapy or the control balloon dilations. With regard to complete blood cell counts, liver function tests, lipid profiles and coagulation tests, there were no differences between the baseline and after radiation. On quantitative coronary angiographic analysis, reference and target artery diameter showed no differences between the 2 groups before, or 4 and 8 weeks after stenting. On histopathologic analysis of groups I and II, the injury score was 1.34±0.09 and 1.32±0.10, the area of internal elastic lamina was 4.99±0.17 mm2 and 4.82±0.20 mm2, and the luminal area was 3.20±0.10 mm2 and 3.45±0.14 mm2, respectively (p=NS). The neointimal area was 1.78±0.11 mm2 in group I and 1.36±0.12 mm2 in group II (p=0.017), and the histopathologic area of stenosis was 35.1±1.6% in group I and 27.6±1.9% in group II (p=0.005). In conclusion, β-radiation of the stented porcine coronary artery using a radioactive 166Ho coated balloon inhibited stent restenosis without any side effects. (author)

  11. Holmium-166-DTPA as a liquid source for endovascular brachytherapy

    International Nuclear Information System (INIS)

    Liquid radiation sources with β emitters have advantages of accurate positioning and uniform dose distribution to the vessel walls to prevent the restenosis of coronary artery. As a liquid radiation source, 166Ho-DTPA was prepared and evaluated its in-vivo pharmacokinetic behavior through animal studies. 166Ho-DTPA was prepared by simple mixing the Holmium with DTPA at room temperature. The radiolabelling yield was 100% when the DTPA/Holmium molar ratio was >2. Radiolabelling of 166Ho-DTPA was not dependent on the pH range of 1.7-7.5. High radiochemical stability (>98%) was maintained over a period of 6 hours even with a radioactivity (∼11.1 GBq/12 mg of DTPA) stored at room temperature. Biodistribution of 166Ho-DTPA in rats and gamma camera images in rabbits showed that 166Ho-DTPA was quickly excreted via the urinary system. The average of Tmax and T1/2 of 166Ho-DTPA in the kidneys of rabbits were 3.71 ± 1.18 min and 9.15 ± 3.15 min. 166Ho-DTPA is a potential liquid radiation source for radiation brachytherapy to prevent the restenosis of the coronary artery using a liquid-filled balloon

  12. Gamma spectrometry and chemical characterization of bioactive glass seeds with Holmium-166 for oncological implants

    International Nuclear Information System (INIS)

    Bioactive glass seeds synthesized by the sol-gel technique with Si:Ho:Ca composition with natural holmium incorporated were irradiated in the TRIGA type nuclear reactor IPR-R1 at 100kW, in the central thimble where the thermal neutron flux is 2.8x1012 n/cm2.s and the epithermal neutron flux is 2.6 X 1011 n/cm2.s . After an 8 hour irradiation time, with an induced activity close to 110MBq/seed, a set of seeds was submitted to Gamma Spectrometry Analysis in a counting system with an HPGe detector, ORTEC electronic instrumentation and a Camberra Multichannel Analyser, to determine all radionuclides present on the sample as well as its individual activities. Special attention was paid on the discrimination of Si, 40Ca, 44Ca, C and Ho as the other expected elements like 48Ca, 2H and 18O were present in traces or have very short half-lives. The second sample was submitted to Plasma spectrometry to determine the 166Ho concentration in weight. The third sample was submitted to an X-ray spectrometry in a JEOL-JXA-8900RL equipment to determine its qualitative chemical composition, in order to evaluate impurities and nominal composition. It was determined that most of the activity, after decaying of short half-life elements, was due to 166Ho present on the sample, with a well characterized β and gamma spectra. The homogeneity of the seeds was tested on the X-ray spectrometry, and verified that there is no discrepancy in composition from distinct seeds or in a same seed. The results are relevant on the investigation of the viability of producing 166Ho radioactive seeds for oncological implants. (author)

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

    International Nuclear Information System (INIS)

    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, β-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-166Ho must be investigated in clinical trials to assure its efficacy and safety on spine tumors treatment (author)

  14. 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)

  15. Preparation and evaluation of holmium-166 ferric hydroxide macroaggregates for radiation synovectomy

    International Nuclear Information System (INIS)

    Aim: The treatment of rheumatoid arthritis using radiopharmaceuticals is an important therapeutic approach. It has been used for more than 40 years to alleviate the pain and swelling of rheumatoid arthritis. Radionuclides such as 153Sm, 90Y and 166Ho were the most interesting ones, because of their short half-lives, low energy beta particle emitters and little gamma ray emission. Ferric hydroxide macroaggregates (FHMA) labeled with 166Ho were studied as a radiation synovectomy agent. Materials and Methods: 166Ho was produced at RA3 reactor of Centro Atomico Ezeiza, by irradiation of natural holmium (100% of 165Ho; 'Spectrographically Standardized'), via the n,γ nuclear reaction. In order to produce labeled particles, a coprecipitation technique of holmium hydroxide Ho(OH)3 and ferric hydroxide Fe(OH)3 was used. The 166Ho-FHMA particles were resuspended in saline and the suspension was sterilized by autoclaving. Pyrogen and sterility tests were performed following known procedures of Pharmacopoeia. Radionuclidic purity control was performed with an high purity germanium high-resolution gamma spectrometry system. Particles in vivo behavior was investigated following intra-articular injection into knees of Wistar rats, normal rabbits and rabbits with antigen induced arthritis (AIA). Gamma camera images of the whole body were analyzed up to 4 and 24 h post injection period. Results: Irradiated samples were counted after 1, 2, 5 and 15 days of irradiation to determine whether other longer lived radionuclides were produced. The only expected isotopic impurity, 166mHo, was no detectable through the gamma spectrometry system. Obtainment efficiency of macroaggregates was greater than 90%. Particle size was determined by optical microscopy and selective filtration (1,2 - 100 μm). At least 90% of FHMA particles were in the range of 20-30 μm. In vitro studies showed minimal (166Ho-FHMA remained into the knee up to 72 h post-injection. A 25% of activity leakage from the knee when 166Ho-chloride was injected. Rabbits studies showed that Ho-166-FHMA was retained in the joint, and that negligible leakage of Ho-166 activity was found in other organs (166Ho-FHMA was simple to perform with high yields. The particles demonstrated high in vitro stability. The radiopharmaceutical remained inside the joint cavity during the study with no detectable leakage. So, 166Ho-FHMA particles are an attractive candidate as a radiation synovectomy agent for evaluation in rheumatoid arthritis patients

  16. Preparation of Holmium -166 Loaded Biodegradable Poly(L-Lactic Acid) Microspheres

    Czech Academy of Sciences Publication Activity Database

    Melichar, František; Kropáček, Martin; Konopková, Marie

    2005-01-01

    Roč. 32, Supplement 1 (2005), S274-S274. ISSN 1619-7070. [Annual Congress of European Association of Nuclear Medicine. 16.10.2005-19.10.2005, Istambul] R&D Projects: GA AV ČR(CZ) 1QS100480501 Institutional research plan: CEZ:AV0Z10480505 Keywords : holmium * raditherapy Subject RIV: CH - Nuclear ; Quantum Chemistry

  17. Evaluation of hela cell lineage response to β radiation from Holmium-166 embedded in ceramic seeds

    Directory of Open Access Journals (Sweden)

    Eduardo Sarmento Valente

    2011-10-01

    Full Text Available This work studied the effects of β radiation of Ho-166 embedded in ceramic seeds on HeLa cells. Methodology consisted in the production of ceramic seeds with holmium-165 by sol-gel route. Chemical and physical characterizations of the seeds were performed. Subsequently, nuclear characterization was performed by gamma spectrometry. Experimental and theoretical activities were defined and initial dose rate were evaluated by MIRD (Medical Internal Radiation Dose Committee methodology. The seeds were placed in confluent culture flasks and remained for six radionuclide half-lives. Biological results were represented by a clean 6 mm diameter area around the seed where the tumour cells were killed. The initial dose rate was 15.5 Gy. h-1. The maximum absorbed dose was 591.3 Gy. The features of the Ho-166 seeds suggested that such ceramic seeds were suitable for high dose rate brachytherapy.

  18. 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)

  19. Cation exchange resins labeled with holmium-166 for treatment of liver malignancy

    International Nuclear Information System (INIS)

    The increasing interest in new therapeutic radiopharmaceuticals is prompting investigators to utilize isotopes with more focused capabilities for treating various tumors, reducing the negative effects on neighboring healthy cells. Local radionuclide therapy using radioactive microspheres is a promising therapy for non-operable group of patients suffering from liver malignancies. Many publications have shown the success of this technique. The emphasis in the present work is the resin-based microspheres labeled with 166Ho. The production of 166Ho is feasible in the IEA-R1 Reactor at IPEN-CNEN/SP, because it does not need high power and high neutron fluxes. Samples of Ho2O3 were irradiated in selected positions of the nuclear reactor IEA-R1 at IPEN/CNEN-SP. The neutron flux was 1.0 x1013 n.s-1.cm-2 for 1 hour. The dissolution of Ho2O3 was studied with different volumes of 0.1M HCl and also varying the heating temperature. The AG50W-X8 200-400 mesh and CM Sephadex C-25 cation exchange resins were labeled with 166Ho. The retention of 166Ho in the resins was studied and also its stability. The results of the dissolution experiments of Ho2O3 showed that there is a direct relation between the increasing volumes needed to dissolve higher masses, and also the positive effect of raising the temperature. The results show very good retention of 166Ho in both columns, even when high volumes of 0.1M HCl are passed through the column containing the resins and its good stability towards saline solution, PBS solution and glucose.Although the resins employed in this work did not have the right particle size (20-50μm), the chemical behavior showed the very good labeling of the resins with 166Ho, and its stability. (author)

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

    International Nuclear Information System (INIS)

    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 TherasphereR or SIR-SpheresR, 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 166Ho being developed at IPEN-CNEN/SP and coordinated by the Radiopharmacy Directory. 166Ho(t1/2=26.8 h) is a beta minus emitter (Emax=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 166Ho, it showed the essential characteristics for liver therapy. Preliminary results of the preparation of glass-based microspheres labeled with 165Ho showed that 5% of Ho2O3 was incorporated in an aluminosilicate glass, through the process of spheronization by flame, which produced spherical microspheres with 20-40μm particle size. The preparation of biodegradable material, polymer-based microspheres, is in its initial stage and the objective is to prepare and label with 165Ho 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)

  1. 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)

  2. Complexation behaviour of DADCA and DAPDA with dysprosium-166/holmium-166 parent daughter system and its potential for use in radioimmunotherapy

    International Nuclear Information System (INIS)

    Full text: A novel approach for the delivery of therapeutic doses from 166Ho to cancerous tissue is via the decay of its parent, 166Dy. When designing radioimmunoconjugte, a crucial question is to determine whether the ligand used in the radiolabeling process is capable of holding the 166Ho on decay of the parent, 166Dy. In this study, two pendant arm macrocycles 1, 10-Diaza-4, 7, 13, 16-tetraoxacyclooctadecane-N, N'-diacetic acid, (DACDA) and 1, 10-Diaza-4, 7, 13-trioxacyclopentadecane-N, N'-diacetic acid, (DAPDA) that were reported to forms reasonably stable complexes with Dy and Ho, were synthesised. The synthesis of the two pendant arm macrocycles was first attempted using methods outlined by Chang and Rowland. The yields obtained through this method were low (10 % for both ligands) and it was considered important to investigate alternative approaches to the synthesis. The new method involved an alkylation reaction in the presence of acetonitrile and sodium bicarbonate. The method took considerably less time and the yields increased to 88 %. The ligands were characterised using 1H NMR, 13C NMR and mass spectrometry. The chemical and radiolytic stabilities of 166Dy and 166Ho complexes of the two ligands were investigated at pH = 5 and the ligands potential for use in the in vivo generator system evaluated

  3. Preparation and Quality Control of 166-Ho--Macroaggregates for Radiosynoviorthesis

    Czech Academy of Sciences Publication Activity Database

    Kropáček, Martin; Melichar, František; Šrank, Jiří; Mirzajevová, Marcela; Klejzarová, Michaela; Kraft, O.; Kašpárek, R.; Záhlava, J.; Chodacki, A.

    2007-01-01

    Roč. 22, Č. 3 (2007), s. 450-452. ISSN 1084-9785 R&D Projects: GA AV ČR 1QS100480501 Institutional research plan: CEZ:AV0Z10480505 Keywords : radiosynoviorthesis * Holmium-166 * radionuclide synovectomy Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.725, year: 2007

  4. Preparation of .sup.166./sup.Ho-Macroaggregates and .sup.166./sup.Ho-chitosan for the endoradiotherapy

    Czech Academy of Sciences Publication Activity Database

    Melichar, František; Kropáček, Martin; Eigner-Henke, Kateřina; Křížová, V.; Konopková, M.; Lang, O.; Mirzajevová, Marcela

    2002-01-01

    Roč. 1, č. 2 (2002), s. 314. ISSN 1450-1147. [Abstracts of the Congress of the World Federation of Nuclear Medicine and Biology.. 29.09.2002-02.10.2002, Santiago] R&D Projects: GA MZd NM6828; GA AV ČR KSK4055109 Keywords : Holmium -166 * radionuclide synovectomy Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

  5. Preparation of .sup.166./sup.Ho-Macroaggregates and .sup.166./sup.Ho-Chitosan for the Radiotherapy

    Czech Academy of Sciences Publication Activity Database

    Kropáček, Martin; Melichar, František; Mirzajevová, Marcela

    2002-01-01

    Roč. 29, č. 2 (2002), s. 382. ISSN 1619-7070 R&D Projects: GA MZd NM6828; GA AV ČR KSK4055109 Keywords : Holmium -166 * 166 Ho-macroaggregates * 166 Ho-chitosan Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

  6. Radiolanthanide labeled compounds as radiopharmaceuticals for radio-synoviorthesis

    Czech Academy of Sciences Publication Activity Database

    Melichar, František; Kropáček, Martin; Šrank, Jiří; Mirzajevová, Marcela; Beran, Miloš; Zimová, Jana; Eigner-Henke, Kateřina; Forsterová, Michaela; Kraft, O.

    2007-01-01

    Roč. 6, č. 1 (2007), s. 45-45. ISSN 1450-1147 R&D Projects: GA AV ČR 1QS100480501 Institutional research pla n: CEZ:AV0Z10480505 Keywords : radiosynoviorthesis * holmium-166 Subject RIV: FR - Pharmacology ; Medidal Chemistry

  7. 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

  8. 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

  9. 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...

  10. Magnetic resonance and nuclear imaging combined with therapy of tumours using 166Ho-loaded particles

    International Nuclear Information System (INIS)

    Cancer treatment with holmium-166 (166Ho) has clear advantages over other radionuclides for therapeutic purposes, because holmium is the only element which can a) be neutron-activated to a beta- and gamma-emitter with a logistically favorable half-life and b) be visualized by MRI. Since the chemical properties of the other lanthanides and a few other elements are similar to those of holmium, the knowledge gained using holmium-loaded carrier particles can probably applied to specific treatment/diagnostic needs

  11. Synthesis and applications of isotopically labelled compounds 1994. Proceedings

    International Nuclear Information System (INIS)

    The 5th International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, 1994, concentrated on the following topics: - the synthesis, analysis and applications of organic compounds labelled with hydrogen and tritium, the production of stable radioactive isotopes such as cobalt 60, germanium 68, holmium 166, dysprosium 166 and tungsten 188; the synthesis of organic compounds labelled with short-lived isotopes such as carbon 11. The uses of isotopes in agriculture, nutrition, pharmaceutical research, pharmacology, medicine and biological pathways was discussed. The final section reviews the regulations governing the safety, handling and disposal of radioisotopes worldwide. (UK)

  12. 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

  13. Preparation and evaluation of [166Ho] holmium-dimethyl diethylenetriaminepentaaceticacid (DMDTPA) as potential radiopharmaceutical for endovascular radiation therapy (EVRT)

    International Nuclear Information System (INIS)

    Holmium-166 with its favorable radiation characteristics could be used in endovascular radionuclide therapy (EVRT) technique in liquid filled low-pressure balloon angioplasty. 166Ho-dimethyl di ethylene triamine penta acetic acid (DMDTPA) was prepared and its biodistribution carried out to evaluate its suitability as an EVRT formulation. DMDTPA was synthesized, characterized and was complexed with 166Ho. The complex was stable at 37 deg. C in human serum environment and at room temperature for 48 h. Biodistribution studies in mice revealed rapid renal clearance (∼90% of the injected dose in 30 min p.i.) with insignificant retention in any of the major organs including bone. The studies show that 166Ho-DMDTPA is a good formulation which can be explored as an EVRT source

  14. 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

  15. 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

  16. Role of labeled and free lanthides in the management of metastatic bone disease

    International Nuclear Information System (INIS)

    Full text: Different radiopharmaceuticals are being used for the management of metastatic bone diseases. This article relates the comparison of therapeutic beta emitter radionuclides of Lutetium-177, Samarium-153 and Holmium-166 complexes to bone seeking phosphonate ligand of ethylenediamine tetramethylene phosphonic acid (EDTMP) with free chlorides of all these radionuclides. Objective: Objective of our study is to formulate and evaluate Lutetium-177, Holmium-166 and Samarium-153 labeled EDTMP and then compare the results of biodistribution free lanthides of these radionuclides. Materials and Methods: All the radionuclides were prepared by n, . reaction. Quality control was checked by paper chromatography and paper electrophoresis. Various parameters were optimized to formulate these radiopharmaceuticals with maximum labeling efficiency. Sprague-Dawley male rats were used for biodistribution and imaging study. Results: 177Lu-EDTMP showed that the complex can be prepared with radiochemical purity >96% at pH 7.5. The labeling efficiency of 153Sm-EDTMP was found to be > 98% at pH 7.5 incubated for 20 minutes at room temperature. 166Ho-EDTMP showed that the complex can be prepared with radiochemical purity >90% at pH 7.5. Among biodistribution study for all these radiopharmaceuticals, skeletal uptake was found to be maximum for 177Lu-EDTMP All the labelled radiopharmaceuticals showed good renal and rapid blood clearance. The biodistribution study of free radionuclides showed significant uptake of activity by soft tissues including lungs, liver and spleen, with minimal uptake in the skeletal system Conclusion: Therefore, it was concluded that labeled complexes of these lanthides can be used effectively in the therapy for bone pain palliation, due to the maximum affinity of skeletal system for the labeled complexes. However, chlorides of the lanthides cannot be used for bone pain palliation due to their poor skeletal localization and accumulation of radionuclides in the

  17. Intra-Arterial Radionuclide Therapies for Liver Tumors.

    Science.gov (United States)

    Bozkurt, Murat Fani; Salanci, Bilge Volkan; Uğur, Ömer

    2016-07-01

    Intra-arterial radionuclide therapies serve essentially as internal radiation treatment options for both primary and metastatic liver tumors, which imply delivering implantable radioactive microspheres into branches of hepatic arteries that feed liver tumors to provide a high dose of targeted radiation to tumor tissue, while sparing the healthy liver tissue from hazardous effects of radiation. The principle of this therapeutic option depends on the unique preferential arterial supply of malignant liver tumors in contrast with mostly portal venous supply of normal hepatocytes as well as excess amount of arterial neovascularization in the tumor bed. Therefore, intra-arterial radionuclide therapy can provide very high radiation exposure to tumor tissue, which is impossible to reach with external radiation therapy due to serious side effects and moreover, radiation can be targeted to tumor tissue selectively with less side effects. Yttrium-90 (Y-90), a high-energetic beta emitter is the most preferred radionuclide, which is used to label microspheres. Two types of Y-90 microspheres are commercially available that are made of resin and glass. Many studies in the literature have demonstrated that Y-90 microsphere therapy is an efficient and safe locoregional therapeutic option for unresectable primary and metastatic liver tumors such as hepatocellular carcinoma and liver metastases from colorectal cancer and breast cancer as well as neuroendocrine tumors. Furthermore, limited number of studies has reported its use in some relatively uncommon metastatic liver tumors from melanoma, pancreatic, renal, and lung cancer. Besides Y-90 microspheres, Iodine-131 lipiodol, Rhenium-188 lipiodol, Rhenium-188 microspheres, Holmium-166 chitosan, and Holmium-166 microspheres have been introduced as alternative radiopharmaceuticals for intra-arterial therapy for liver tumors. PMID:27237442

  18. Evaluation of the therapeutic effect of hydroxyapatite particles labeled with Ho166 in rats with acute and chronic arthritis

    International Nuclear Information System (INIS)

    The therapeutic effect of an intraarticular injection of hydroxyapatite particles labeled with Holmium-166 ( Ho166HA) 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 intraarticular injection of 0,5 μCi of Ho166-HA (day 0, 4, 9, 14, 19, 30). Also a biological distribution study was done at 4, 24 and 48 hours in different organs, through the counting of its radiation. The results of the biological distribution showed that a very high percent of the injected activity remains inside the joint, with minimal activity in other organs, which indicates that the extra articular leakage is very low. The evaluation of the articular perimeter, demonstrated that Ho166-HA has a therapeutic effect , which was shown by comparing the control group (6.42 ±0.43 cm right knee; 6.14 ±0.31 cm left knee) with the acute arthritis group (5.11 ±0.3 cm right knee; 4.95 ±0.39 cm left knee) with significantly statistical values (p≤0,01); also the control group was compared with the chronic arthritis group (5.6 ±0.56 cm right knee; 5.47 ±0.51 cm left knee), 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

  19. Microsphere radio embolization of liver malignancies: current developments

    International Nuclear Information System (INIS)

    The worldwide incidence of hepatic malignancies, both primary and secondary, exceeds 1 000 000 new cases each year. The poor prognosis of patients suffering from hepatic malignancies has lead to the development of a liver directed therapy which consists of intra-arterial administration of radioactive particles through a catheter. Yttrium-90 (90Y) microspheres are increasingly applied for this purpose, and up to now nearly all clinical experience with radio embolization has been obtained with these microspheres. The response rate is very promising in both patients with primary and metastatic liver malignancies. Currently, two commercially available 90Y microsphere devices are in use clinically, both as a first-line treatment and in a salvage setting. Unfortunately, the use of a pure β-emitter like 90Y hampers acquisition of high quality nuclear images for pre-treatment work-up and follow-up. This issue was addressed by the development of holmium-166 (166Ho) and rhenium-188 (188Re) microspheres, which emit both b-particles for therapeutic purposes and g-photons for nuclear imaging. Moreover, since holmium is paramagnetic it allows for magnetic resonance imaging. 166Ho loaded poly(L-lactic acid) microspheres have been thoroughly investigated in a preclinical setting, and recently the first clinical results for 188Re microspheres were reported. This review provides an overview of the current status and (pre-)clinical developments of radioactive microspheres for treatment of liver malignancies.

  20. 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.

  1. Treatment of Bowen's disease with a specially designed radioactive skin patch

    International Nuclear Information System (INIS)

    Bowen's disease can be treated by various methods, including surgical excision, cryosurgery, laser ablation, curettage, Mohs' microsurgery and ionizing radiation. Radiotherapy has been a useful therapeutic modality in the treatment of Bowen's disease and other skin cancers in areas which are difficult to excise, especially the central areas of the face, including eyelids, nose and lips. To overcome some of the disadvantages of external radiotherapy, a specially designed skin patch coated with high-energy beta-emitter holmium-166 was made for topical application at our institute. Twenty-nine sites of Bowen's disease in eight patients, confirmed by skin biopsy, were treated with 166Ho patches. The patches were applied to the surface of skin cancers for 30-60 min for a total radiation dose of 35 Gy (3500 rads). One to two weeks after application of the 166Ho patch, desquamation, erythema or erosion developed in treated sites, but these acute radiation reactions healed gradually with epithelial regeneration, and they showed good functional and cosmetic results without any complications. Follow-up biopsies were performed 1-5 months after 166Ho patch therapy, and they did not show any signs of Bowen's disease. One to two years after treatment with 166Ho skin patches, there were no recurrences of Bowen's diseases and no late complications. The 166Ho patch is an effective and convenient alternative method for the treatment of Bowen's disease that yields good cosmetic and functional results. (orig.)

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

    International Nuclear Information System (INIS)

    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

  3. Hot atom reactions resulting from (n, γ) in holmium compound tris (2,2,6,6-tetramethyle-3,5-heptane dionato) holmium (III)

    International Nuclear Information System (INIS)

    The behavior of a recoiled 166Ho resulting from the reaction 165Ho(n,γ)166Ho in the compound Tris (2,2,6,6-tetramethyle-3,5-heptanedionato) Holmium(III) was investigated. Irradiation was carried out in a low flux research reactor (the Syrian Miniature Nuclear Source Reactor MNSR) with a maximum thermal neutron flux of 1x1012 n.cm-2.s-1. Chemical separation methods were developed to separate the recoil product from the irradiated compound. It was found that the paper chromatography gave the best results where the compound was developed with toluene. The study showed that the retention value of holmium 166Ho was equal to 45%. It was also found that the process of purification and the irradiation of samples in an inert atmosphere had a neglected impact on the retention value of the studied compound. This was attributed to the presence of oxygen in the structure of the molecule, where it is released during the nuclear recoil process and play scavenger role.(author)

  4. 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. PMID:26691104

  5. Production and quality control of 166 Ho

    International Nuclear Information System (INIS)

    Full text: Radioisotope production is one of the most important sectors in the mid and long term program of nuclear technology development. Therapeutic radiopharmaceuticals allow nuclear physicians to treat disease by attacking only the affected cells. The advantage of nuclear therapeutic over other therapies is that nuclear therapy can eliminate cancerous cells almost without harming healthy cells. Nuclear therapy would greatly improve quality of live by lowering the overall cost of the hospital, and reducing the time a patient stays in the hospital, and reducing the pain and suffering experienced by the patient. Several new radionuclides and carriers have recently been studied for treatment of various joint disorders. Ho-166 is a radionuclide with excellent physical properties for therapeutic application. Holmium-166 is produced by neutron capture on 100% abundant, stable holmium-165 with thermal neutron and resonance neutron cross section of 61.2 barns, respectively. It decays with 26.83 h half-life by emission of 1.855 MeV(51%) and 1.776 MeV (48%). Ho-166 also emits 80.5 keV gamma-ray in 6.2% abundance and, thus, is imageable by conventional techniques. Holmium-166 is utilized in radiotherapeutic applications such as radioimunospecific pharmaceuticals, bone marrow ablation, and radiation synovectomy. The radionuclide 166Ho is successfully produced by 165Ho (n,γ)166Ho reaction in the Nuclear Research Reactor (5 MW) at the neutron flux density 5*1013 n.cm-2.s-1. This study was focused to the preparation and quality control (especially of the radiochemical and radionuclide control) of the 166Ho. References: 1. Han .H .S, et al.: Current status and future plan for the production of radioisotopes using HANARO Research Reactor: journal of radioanalytical and Nuclear Chemistry, vol. 257, No.1 (2003) 47-51.; 2. Kyug Bae Park, Production Ho-166, IAEA-TECDOC-1340, IAEA: 71-74, 2003.; 3. Heuft-Dorenbusch L., et al.: Yttrium radiosynovectomy in the treatment of knee

  6. 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

  7. Removal of chloroform from biodegradable therapeutic microspheres by radiolysis.

    Science.gov (United States)

    Zielhuis, S W; Nijsen, J F W; Dorland, L; Krijger, G C; van Het Schip, A D; Hennink, W E

    2006-06-01

    Radioactive holmium-166 loaded poly(l-lactic acid) microspheres are promising systems for the treatment of liver malignancies. These microspheres are loaded with holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method using chloroform. After preparation the microspheres (Ho-PLLA-MS) are activated by neutron irradiation in a nuclear reactor. It was observed that relatively large amounts of residual chloroform (1000-6000 ppm) remained in the microspheres before neutron irradiation. Since it is known that chloroform is susceptible for high-energy radiation, we investigated whether neutron and gamma irradiation could result in the removal of residual chloroform in HoAcAc-loaded and placebo PLLA-MS by radiolysis. To investigate this, microspheres with relatively high and low amounts of residual chloroform were subjected to irradiation. The effect of irradiation on the residual chloroform levels as well as other microsphere characteristics (morphology, size, crystallinity, molecular weight of PLLA and degradation products) were evaluated. No chloroform in the microspheres could be detected after neutron irradiation. This was also seen for gamma irradiation at a dose of 200 kGy phosgene, which can be formed as the result of radiolysis of chloroform, was not detected with gas chromatography-mass spectrometry (GC-MS). A precipitation titration showed that radiolysis of chloroform resulted in the formation of chloride. Gel permeation chromatography and differential scanning calorimetry showed a decrease in molecular weight of PLLA and crystallinity, respectively. However, no differences were observed between irradiated microsphere samples with high and low initial amounts of chloroform. In conclusion, this study demonstrates that neutron and gamma irradiation results in the removal of residual chloroform in PLLA-microspheres. PMID:16549282

  8. Treatment of Bowen's disease with a specially designed radioactive skin patch

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yae Lee; Bang, Dongsik; Lee, Jung Bock; Lee, Min-Geol [Department of Dermatology, Yonsei University College of Medicine, Seoul (Korea); Lee, Jong Doo [Division of Nuclear Medicine, Department of Diagnostic Radiology, Yonsei University, College of Medicine, Seoul (Korea); Park, Kyung Bae [Hanaro Center, Korea Atomic Energy Research Institute, Taejon (Korea)

    2000-07-01

    Bowen's disease can be treated by various methods, including surgical excision, cryosurgery, laser ablation, curettage, Mohs' microsurgery and ionizing radiation. Radiotherapy has been a useful therapeutic modality in the treatment of Bowen's disease and other skin cancers in areas which are difficult to excise, especially the central areas of the face, including eyelids, nose and lips. To overcome some of the disadvantages of external radiotherapy, a specially designed skin patch coated with high-energy beta-emitter holmium-166 was made for topical application at our institute. Twenty-nine sites of Bowen's disease in eight patients, confirmed by skin biopsy, were treated with {sup 166}Ho patches. The patches were applied to the surface of skin cancers for 30-60 min for a total radiation dose of 35 Gy (3500 rads). One to two weeks after application of the {sup 166}Ho patch, desquamation, erythema or erosion developed in treated sites, but these acute radiation reactions healed gradually with epithelial regeneration, and they showed good functional and cosmetic results without any complications. Follow-up biopsies were performed 1-5 months after {sup 166}Ho patch therapy, and they did not show any signs of Bowen's disease. One to two years after treatment with {sup 166}Ho skin patches, there were no recurrences of Bowen's diseases and no late complications. The {sup 166}Ho patch is an effective and convenient alternative method for the treatment of Bowen's disease that yields good cosmetic and functional results. (orig.)

  9. 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.

  10. 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.

  11. 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

  12. 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

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

    International Nuclear Information System (INIS)

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

  14. [166Dy]Dy/166Ho hydroxide macroaggregates: an in vivo generator system for radiation synovectomy

    International Nuclear Information System (INIS)

    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 μm 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 β- 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 during

  15. A Dosimetric Study of Radionuclide Therapy for Bone Marrow Ablation.

    Science.gov (United States)

    Bayouth, John Ellis

    In a phase I clinical trial, six multiple myeloma patients, who were non-responsive to conventional therapy and were scheduled for bone marrow transplantation, received Holmium-166 (166Ho) labeled to a bone seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane -1,4,7,10-tetramethylene-phosphonic acid), for the purpose of bone marrow ablation. The specific aims of my research within this protocol were to evaluate the toxicity and efficacy of 166Ho DOTMP by quantifying the in vivo pharmacokinetics and radiation dosimetry, and by correlating these results to the biologic response observed. The reproducibility of pharmacokinetics from multiple injections of 166 Ho DOTMP administered to these myeloma patients was demonstrated from both blood and whole body retention. The skeletal concentration of 166 Ho DOTMP was heterogenous in all six patients: high in the ribs, pelvis, and lumbar vertebrae regions, and relatively low in the femurs, arms, and head. A novel technique was developed to calculate the radiation dose to the bone marrow in each skeletal ROI, and was applied to all six 166 Ho DOTMP patients. Radiation dose estimates for the bone marrow calculated using the standard MIRD "S" factors were compared with the average values derived from the heterogenous distribution of activity in the skeleton (i.e., the regional technique). The results from the two techniques were significantly different; the average of the dose estimates from the regional technique were typically 30% greater. Furthermore, the regional technique provided a range of radiation doses for the entire marrow volume, while the MIRD "S" factors only provided a single value. Dose volume histogram analysis of data from the regional technique indicated a range of dose estimates that varied by a factor of 10 between the high dose and low dose regions. Finally, the observed clinical response of cells and abnormal proteins measured in bone marrow aspirates and peripheral blood samples were compared with

  16. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-01

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

  18. 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

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

    International Nuclear Information System (INIS)

    Aim: Biotin is a vitamin found in low concentration in blood and tissue. In radioimmunodiagnosis and radioimmunotherapy practice, the pre-targeting avidin-biotin strategy has shown that target-to-nontarget radioactivity ratios can be significantly improved. In addition, the biotin content of cancerous tumors is higher than that of normal tissue and it has been found in the cellular nucleus due to a specific transfer of biotin to histones by human serum biotinidase. Because of its nuclear properties, the 166Dy/166Ho radionuclide pair can be considered as an in vivo generator system. The aim of this work was to synthesize 166Dy/166Ho-DTPA-bisBiotin to evaluate its potential as a new radiopharmaceutical for targeted radiotherapy. Material and Methods: Dysprosium-166/Holmium-166 chloride was obtained by neutron irradiation of 50 mg of 99% enriched 164Dy2O3 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, 100 μL of 12 N chloride acid were added and the mixture stirred for 3 min. To this suspension 1.0 mL of injectable water were added and heated for 2 min at 900C. The biotin used in this investigation was diethylenetriaminepentaacetic-α,ω-bis(biocytinamide)(DTPA-bisBiotin, Sigma). Sterile and apyrogenic V-vial was prepared to contain 16.0 mg (1.52 x 10-4 mmol) of the DTPA-bisBiotin in 4.0 mL of 0.05 M bicarbonate buffer (pH 8.5), then 50 μL of the radiochloride solution were added to the preparation. TLC aluminum cellulose sheets were used as the stationary phase and a ternary mixture of methanol: water: ammonium hydroxide (20:40:2) as the mobile phase. 166Dy/166Ho-DTPA-bisBiotin traveled with the solvent front Rf 0.9-1.0 and the Dy+3/Ho+3 species remained at the origin (Rf 0.0). HPLC reverse phase was also used to evaluate radiochemical purity. The biological integrity of labeled biotin was achieved evaluating its avidity for avidin in an agarose column

  20. 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

  1. Effective local control of malignant melanoma by intratumoural injection of a beta-emitting radionuclide

    International Nuclear Information System (INIS)

    In this study, therapeutic effect, morphological alterations and biological responses to the high-dose continuous irradiation delivered using this new technique were evaluated in an animal model with B16 melanoma. For evaluation of the therapeutic effect, 92 C57BL/6 mice with B16 melanoma were divided into four groups. In each group, intratumoural injections were performed when the tumour measured approximately 1 cm along its long axis. Group 1 (n=25) received 0.3 ml of normal saline, group 2 (n=15) 37 MBq of carrier-free holmium-166 in 0.3 ml saline, group 3 (n=27) 185 MBq of 166Ho in 0.3 ml saline and group 4 (n=25) 185 MBq of 166Ho in 0.5 ml saline. In addition, another 30 mice were used for morphological and biological analysis of the radiation effect. These 30 mice were injected with 185 MBq of 166Ho in 0.3 ml saline, and five were sacrificed at each of the following six time points: before injection and 1, 2, 3, 6 and 14 days post injection. For visual side-by-side comparison, melanoma cells were inoculated bilaterally into the back of ten additional mice, and 185 MBq of 166Ho in 0.3 ml of saline or an equal volume of normal saline was injected separately into the bilateral tumours. Nine days after inoculation of melanoma cells, mean tumour volume reached 492.5-631.9 mm3. Tumours of the control group (group 1) showed rapid growth, and the mean tumour volume reached approximately 30 times the original volume. None of the control group lived for more than 16 days following the injection of normal saline. On the other hand, mean tumour volume of the treated groups showed a gradual decrease, and 67%-74% of the treated animals were alive when all the control animals had died. The median survival of the control group was 9 days following injection, whereas it was 29 days in group 2, 33 days in group 3 and 33 days in group 4. The survival rate of group 3 was higher than that of groups 2 and 4, but statistical significance was not observed. H and E stain of the