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Published on: May 5, 2021
A trithiol bifunctional chelate for 72,77As: A matched pair theranostic complex with high in vivo stability
Yutian Feng1, Anthony J DeGraffenreid2, Michael D Phipps1
1Department of Chemistry, University of Missouri, Columbia, MO 65211, USA.
Introduction:
Trithiol chelates are suitable for labeling radioarsenic (72As: 2.49 MeV β+, 26 h; 77As: 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 77As, its in vitro stability assessed, and biodistribution studies were performed in CF-1 normal mice of free [77As]arsenate and 77As-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 77As resulted in over 90% radiochemical yield of 77As-trithiol-BBN, which was stable for over 48 h. Biodistribution studies were performed with both free [77As]arsenate and Sep-Pak® purified 77As-trithiol-BBN(7-14)NH2. Compared to the fast renal clearance of free [77As]arsenate, 77As-trithiol-BBN(7-14)NH2 demonstrated increased retention with clearance mainly through the hepatobiliary system, consistent with the lipophilicity of the 77As-trithiol-BBN(714)NH2 complex.
Conclusion:
The combined in vitro stability of 77As-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.
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