A trithiol bifunctional chelate for 72,77 As: A matched pair theranostic complex with high in vivo stability.

INTRODUCTION: Trithiol chelates are suitable for labeling radioarsenic (72 As: 2.49 MeV β+ , 26 h; 77 As: 0.683 MeV β- , 38.8 h) to form potential theranostic radiopharmaceuticals for PET imaging and therapy. To investigate the in vivo stability of trithiol chelates complexed with no carrier added (nca) radioarsenic, a bifunctional trithiol chelate was developed, and conjugated to bombesin(7-14)NH2 as a model peptide.

METHODS: A trithiol-BBN(7-14)NH2 bioconjugate and its arsenic complex were synthesized and characterized. The trithiol-BBN(7-14)NH2 conjugate was radiolabeled with 77 As, its in vitro stability assessed, and biodistribution studies were performed in CF-1 normal mice of free [77 As]arsenate and 77 As-trithiol- BBN(7-14)NH2 .

RESULTS: The trithiol-BBN(7-14)NH2 conjugate, its precursors and its As-trithiol-BBN(7-14)NH2 complex were fully characterized. Radiolabeling studies with nca 77 As resulted in over 90% radiochemical yield of 77 As-trithiol-BBN, which was stable for over 48 h. Biodistribution studies were performed with both free [77 As]arsenate and Sep-Pak® purified 77 As-trithiol-BBN(7-14)NH2 . Compared to the fast renal clearance of free [77 As]arsenate, 77 As-trithiol-BBN(7-14)NH2 demonstrated increased retention with clearance mainly through the hepatobiliary system, consistent with the lipophilicity of the 77 As-trithiol-BBN(714)NH2 complex.

CONCLUSION: The combined in vitro stability of 77 As-trithiol-BBN(7-14)NH2 and the biodistribution results demonstrate its high in vivo stability, making the trithiol a promising platform for developing radioarsenic-based theranostic radiopharmaceuticals.