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)NH ₂ as a model peptide.
Methods: A trithiol-BBN(7-14)NH ₂ bioconjugate and its arsenic complex were synthesized and characterized. The trithiol-BBN(7-14)NH ₂ 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)NH ₂ .
Results: The trithiol-BBN(7-14)NH ₂ conjugate, its precursors and its As-trithiol-BBN(7-14)NH ₂ 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)NH ₂ . Compared to the fast renal clearance of free [ ⁷⁷ As]arsenate, ⁷⁷ As-trithiol-BBN(7-14)NH ₂ demonstrated increased retention with clearance mainly through the hepatobiliary system, consistent with the lipophilicity of the ⁷⁷ As-trithiol-BBN(714)NH ₂ complex.
Conclusion: The combined in vitro stability of ⁷⁷ As-trithiol-BBN(7-14)NH ₂ and the biodistribution results demonstrate its high in vivo stability, making the trithiol a promising platform for developing radioarsenic-based theranostic radiopharmaceuticals.
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