Evaluation of 188Re- IBA as a novel radiopharmaceutical for bone marrow ablation.

In this study, Ibandronate as a third generation of bisphosphonates was labeled with rhenium-188 radionuclide. Production and quality control of 188Re-IBA radiopharmaceutical was investigated. The radiation absorbed dose of this radiopharmaceutical was evaluated for adult male based on biodistribution data in mice using the RADAR and Sparks and Aydogan methodologies. The 188Re-IBA was produced with more than 96% radiochemical purity. The highest value of %ID/g was related to bone with 7.11% at 12 h post-injection. About 48% of injected activity was cumulated on the surface of bone tissue 48 h post-injection. The imaging studies confirmed the biodistribution pattern. Radiation absorbed doses of red bone marrow and osteogenic cells were estimated to about 0.39 and 0.71 mGy MBq-1, respectively. The maximum administrated activity was obtained 73.1 MBq kg-1 (2.0 mCi kg-1) of body weight. Effective dose was evaluated about 0.09 mSv MBq-1. The results were compared with other clinically used bone pain palliation radiopharmaceuticals. It was concluded that the 188Re-IBA radiopharmaceutical has a great tendency to be absorbed in bone tissue and it can provide sufficient care for bone marrow ablation with low undesired dose to other normal organs.

Estimation of Human Absorbed Dose of 188Re-Hynic-Bombesin Based on Biodistribution Data in Rats.

BACKGROUND: HYNIC-Bombesin (BBN) is a potential peptide for targeted radionuclide therapy in gastrin-releasing peptide receptor (GRPr)-positive malignancies. The 188Re-HYNICBBN is a promising radiopharmaceutical for use in prostate cancer therapy. OBJECTIVE: The aim of this study was to estimate the absorbed dose due to 188Re-HYNIC-BBN radio-complex in human organs based on bio-distribution data of rats. METHODS: In this research, using bio-distribution data of 188Re-HYNIC-BBN in rats, its radiation absorbed dose of the adult human was calculated for different organs based on the MIRD dose calculation method. RESULTS: A considerable equivalent dose amount of 188Re-Hynic-BBN (0.093 mGy/MBq) was accumulated in the prostate. Moreover, all other tissues except for the kidneys and pancreas approximately received insignificant absorbed doses. CONCLUSION: Since the acceptable absorbed dose for the complex was observed in the prostate, 188Re-Hynic-Bombesin can be regarded as a new potential agent for prostate cancer therapy.

Human Absorbed Dose Evaluation of [177Lu]Lu-IBA as a Bone Palliative Candidate.

The role of lutetium-177 among bone-seeking radionuclides in targeted therapy is noteworthy. The clinical pharmacokinetics of ibandronate (IBA) indicates that this bisphonate has powerful bone mineral affinity. The aim of this study was to evaluate of [177Lu]Lu-IBA efficacy as a new compound.The [177Lu]Lu-IBA was prepared by radiolabeling of IBA ligand to 177LuCl3 that was obtained by thermal neutron irradiation of enriched Lu2O3 sample. Produced [177Lu]Lu-IBA with high radiochemical purity was administered intravenously to mice. Biodistribution data were collected at 1, 4, 24, 48 h and 7 d post injections. With calculating accumulated activities in each organ and extrapolating mouse's organs to human's organs by the RADAR method and using OLINDA/EXM software the injected dose in various human organs was achieved.[177Lu]Lu-IBA was produced with radiochemical purity nearly 96 %. Its biodistribution data showed the high uptake and durability in the skeletal tissues without significant uptake in other major organs.The results showed that [177Lu]Lu-IBA has considerably good properties as a bone-seeking radiopharmaceutical and therefore can be a candidate for bone pain palliative therapy in skeletal metastases; however, further biological studies are still needed.

ESTIMATION OF HUMAN DOSE OF 188/186RE-HEDP COCKTAIL BASED ON OLINDA/EXM AND DISTRIBUTION DATA IN RATS.

188Re and 186Re are two applicable rhenium medical radioisotopes with complementary features that make them beneficial for different sizes of tumours. The aim of this study is to investigate 188/186Re-HEDP efficacy as a cocktail by calculating absorbed radiation dose in human organs based on biodistribution data obtained by injecting it to normal rats. Three rats were sacrificed at different time intervals and the percentage of injected dose per gram of each organ was measured by direct counting from rat data. By calculating accumulated activities in each organ and extrapolating rat data to human data by the radiation dose assessment resource method and by using OLINDA/EXM software, the injected dose in various human organs was obtained. The calculated absorbed dose showed that the 188/186Re-HEDP has noticeable properties that can be more helpful in comparison with using each of the rhenium radioisotopes separately.

Developing a new target design for producing 99Mo in a MTR reactor.

99Mo is an important radioisotope and mainly produced using uranium fission reaction in a nuclear reactor. Investigation for probable improvements, especially on target geometry and in-core location of target is the main goal of this research. This is for producing more efficient of 99Mo in a typical Material Testing Reactors (MTRs). A parametric investigation is done focused on the target characteristics such as geometry, location, material, density, heat flux (power density) and also usability in Tehran Research Reactor (TRR) as a MTR case study. Stochastic code MCNPX 2.6.0 along with CFD code ANSYS are used to perform neutronic and thermal-hydraulic analyses. A target with plate type design is specified and proposed as a final and most favorable design. Taking into account the safety criteria, the production yield, the chemical process and radioactive waste, it is demonstrated that the new target design meets the key design requirements without compromising the reactor safety. This research results indicate that the new target gives rise to a higher production of 99Mo using less amount of initial material causing to a reduction in nuclear waste and process difficulties.

An analytical study of effect of the cell proliferation, half-life, and energy of radionuclides in targeted radiotherapy.

AIM: The treatment of the cancers is one of the most important challenges of nuclear medicine. Using targeted radiotherapy has increased the hope for the cure of the cancers. In the targeted radiotherapy, proliferations of tumor cells during radiotherapy are believed to be main reasons of treatment defeat. The aim of this work is the investigation of the cell proliferation on tumor treatment. MATERIALS AND METHODS: For this purpose, two scenarios were considered. The first scenario, in case of the tumor cells nonproliferation, surviving curve of irradiated cells is an exponential function of accumulated dose. The second scenario, Tumor cells proliferate exponentially with a growth constant and all tumor cells are assumed to be proliferating throughout irradiation. RESULTS: In the nonproliferation condition, the surviving fraction of tumor cells decreases with time. In the proliferation cases, at the beginning of the irradiation, the surviving fraction of cells decreases. If the remained fraction of cells is reduced sufficiently by this time, the tumor may be treated. Unless, as the dose rate continues to decrease, the proliferation exceeds from the sterilization and the tumor cell population increases. CONCLUSION: Due to high dose-rate, the shorter decay half-life is more effective in comparison to longer ones.