A New, Second Generation Trithiol Bifunctional Chelate For (72,77)As: Trithiol(B)-(Ser)(2)-Rm2

Trithiol chelates are suitable for labeling radioarsenic (As-72: 2.49 MeV beta(+), 26 h; As-77: 0.683 MeV beta(-), 38.8 h) to form potential theranostic radiopharmaceuticals for positron emission tomography (PET) imaging and therapy. A trithiol(b)-(Ser)(2)-RM2 bioconjugate and its arsenic complex were synthesized and characterized. The trithiol(b)-(Ser)(2)-RM2 bioconjugate was radiolabeled with no-carrier-added As-77 in over 95% radiochemical yield and was stable for over 48 h, and in vitro IC50 cell binding studies of [As-77]As-trithiol(b)-(Ser)(2)-RM2 in PC-3 cells demonstrated high affinity for the gastrin-releasing peptide (GRP) receptor (low nanomolar range). Limited biodistribution studies in normal mice were performed with HPLC purified As-77-trithiol(b)-(Ser)(2)-RM2 demonstrating both pancreatic uptake and hepatobiliary clearance.