Production and evaluation of high specific activity 186Re: An isotope for radioimmunotherapy in cancer treatment

The goal of this research project was to investigate the feasibility of Rhenium-186 (186Re) as an isotope for radioimmunotherapy. 186Re is commonly produced via neutron capture in a reactor. This leads to a product with low specific activity (LSA), which is not optimal for site specific targeting. As such, the possibility of producing high specific activity (HSA) 186Re from a charged particle reaction was investigated. The HSA 186Re was produced via the 186W(p,n) reaction at TRIUMF using the TR13 cyclotron. A dry distillation chemistry method was developed for the separation of trace rhenium from tungsten targets. Antibodies were labeled with both HSA 186Re and reactor produced LSA 186Re using a mercaptoacetyltriglcine chelate, which was synthesized as previously described in the literature. Cell lines that do (R+) and do not (R-) express the IGF receptor were examined for radiosensitivity to external beam irradiation and exposure to free 186Re using traditional methods including vital dye exclusion, clonogenicity and fluorescence activated cell sorting. An antibody known to be specific for the IGF receptor (1H7) was labeled with HSA and LSA 186Re and incubated with both R+ and R- cell lines. Specific antibody binding was assessed. In addition, experiments were conducted at both Oak Ridge National Laboratory using an electron beam plasma ion source and at a TRIUMF with a proof-of-principle cusp ion source test stand to determine the feasibility of producing carrier-free 186Re from a neutron irradiated target. This work demonstrates that 186Re can be produced in high specific activity from the 186W(p,n) reaction. Although yields from the cyclotron reaction were determined to be too low to produce HSA 186Re in patient quantities in an economically feasible manner using current technology, significant quantities could be produced for subsequent experiments. Antibodies were successfully labeled with both HSA and LSA 186Re. No increased binding was observed with the HSA 186Re. A cusp ion source test stand was successfully constructed at TRIUMF and beams of 1012 Re ions per second have been accelerated, illustrating the possibility of producing HSA 186Re from reactor targets.