Introduction: Targeted radiotherapy using the bifunctional chelate approach with Re(V) is challenging because of the susceptibility of monooxorhenium(V)-based complexes to oxidize in vivo at high dilution. A monoamine-monoamide dithiol (MAMA)-based bifunctional chelating agent was evaluated with both rhenium and technetium to determine its utility for in vivo applications.
Methods: A 222-MAMA chelator, 222-MAMA(N-6-Ahx-OEt) bifunctional chelator, and 222-MAMA(N-6-Ahx-BBN(7-14)NH) were synthesized, complexed with rhenium, radiolabeled with Tc and Re (carrier added and no carrier added), and evaluated in initial biological distribution studies.
Results: An IC value of 2.0±0.7nM for ReO-222-MAMA(N-6-Ahx-BBN(7-14)NH) compared to [I]-Tyr-BBN(NH) was determined through competitive cell binding assays with PC-3 tumor cells. In vivo evaluation of the no-carrier added Tc-222-NS(N-6-Ahx-BBN(7-14)NH) complex showed little gastric uptake and blockable pancreatic uptake in normal mice.
Conclusions: The ReO-222-NS(N-6-Ahx-BBN(7-14)NH) complex showed stability in biological media, which indicates that the 222-NS chelator is appropriate for chelating Re in radiopharmaceuticals involving peptides. Additionally, the in vitro cell studies showed that the ReO-222-NS(N-6-Ahx-BBN(7-14)NH) complex (macroscopically) bound to PC3-tumor cell surface receptors with high affinity. The Tc analog was stable in vivo and exhibited pancreatic uptake in mice that was blockable, indicating BB2r targeting.
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| http://dx.doi.org/10.1016/j.nucmedbio.2016.08.017 | DOI Listing |
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