Monooxorhenium(V) complexes with 222-N 2 S 2 MAMA ligands for bifunctional chelator agents: Syntheses and preliminary in vivo evaluation.

Introduction: Targeted radiotherapy using the bifunctional chelate approach with ^186/188 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 ₂ ) were synthesized, complexed with rhenium, radiolabeled with ^99m Tc and ¹⁸⁶ Re (carrier added and no carrier added), and evaluated in initial biological distribution studies.
Results: An IC ₅₀ value of 2.0±0.7nM for ^nat ReO-222-MAMA(N-6-Ahx-BBN(7-14)NH ₂ ) compared to [ ¹²⁵ I]-Tyr ⁴ -BBN(NH ₂ ) was determined through competitive cell binding assays with PC-3 tumor cells. In vivo evaluation of the no-carrier added ^99m Tc-222-N ₂ S ₂ (N-6-Ahx-BBN(7-14)NH ₂ ) complex showed little gastric uptake and blockable pancreatic uptake in normal mice.
Conclusions: The ¹⁸⁶ ReO-222-N ₂ S ₂ (N-6-Ahx-BBN(7-14)NH ₂ ) complex showed stability in biological media, which indicates that the 222-N ₂ S ₂ chelator is appropriate for chelating ^186/188 Re in radiopharmaceuticals involving peptides. Additionally, the in vitro cell studies showed that the ReO-222-N ₂ S ₂ (N-6-Ahx-BBN(7-14)NH ₂ ) complex (macroscopically) bound to PC3-tumor cell surface receptors with high affinity. The ^99m Tc analog was stable in vivo and exhibited pancreatic uptake in mice that was blockable, indicating BB2r targeting.
(Copyright © 2016 Elsevier Inc. All rights reserved.)