Absorbed doses in humans from 188Re-Rituximab in the free form and bound to superparamagnetic iron oxide nanoparticles: Biodistribution study in mice.

Absorbed doses to human organs from 188Re-Rituximab in the free form and bound to superparamagnetic iron oxide nanoparticles were predicted from results of the radiopharmaceutical biodistribution studies in mice by the RADAR method. Overall, equivalent and effective doses to human organs from the radiopharmaceutical on the nanoparticles were higher because of the enhanced permeability and retention effect. Liver, spleen and kidneys received higher equivalent doses than other organs (5.29, 3.70 and 3.06mSv/MBq, respectively, for the free radiopharmaceutical and 6.12, 3.96 and 3.93mSv/MBq for the drug on the nanoparticles).

Preparation and evaluation of APTES-PEG coated iron oxide nanoparticles conjugated to rhenium-188 labeled rituximab.

Radioimmuno-conjugated (Rhenium-188 labeled Rituximab), 3-aminopropyltriethoxysilane (APTES)-polyethylene glycol (PEG) coated iron oxide nanoparticles were synthesized and then characterized. Therapeutic effect and targeting efficacy of complex were evaluated in CD20 express B cell lines and tumor bearing Balb/c mice respectively. To reach these purposes, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using coprecipitation method and then their surface was treated with APTES for increasing retention time of SPIONs in blood circulation and amine group creation. In the next step, N-hydroxysuccinimide (NHS) ester of polyethylene glycol maleimide (NHS-PEG-Mal) was conjugated to the APTES-treated SPIONs. After radiolabeling of Rituximab antibody with Rhenium-188 (T1/2=16.9h) using synthesized N2S4 chelator, it was attached to the APTES-PEG-MAL-SPIONs surface through thiol-maleimide coupling reaction. In vitro evaluation of the 188ReN2S4-Rituximab-SPION-complex thus obtained revealed that at 24 and 48h post-treatment effective cancer cell killing had been achieved. Bio-distribution study in tumor bearing mice showed capability of this complex for targeted cancer therapy. Active and passive tumor targeting strategies were applied through incorporated anti-CD20 (Rituximab) antibody and also enhanced permeability and retention (EPR) effect of solid tumors for nanoparticles respectively.

Development of an electrochemical 188W/188Re generator as a technique for separation and purification of 188Re in radiopharmaceutical applications.

In this study, a simple electrochemical procedure adaptable for using low specific activity 188W for separation and purification of 188Re from 188W to obtain no carrier added (NCA) 188Re is developed. The electrochemical parameters were optimized to maximize the 188Re electrodeposition yield with minimal 188W contamination. Two cycle electrolysis procedure was developed. The first electrochemical cell was used for separation of 188Re and in the second electrochemical cell, separation and purification of 188Re with >90% deposition yield of 188Re and minimal contamination of 188W (<10-4%) was achieved. The overall electrodeposition yield of 188Re was >90% with >99% radionuclidic purity and >99% radiochemical purity suitable for radiopharmaceutical applications. Furthermore, the performance of the generator remained consistent during a period of 69 days, one half-life of 188W, when the electrochemical separation procedure was performed frequently, at least once in 5 days.