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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Feng, Y; DeGraffenreid, AJ; Phipps, MD; Rold, TL; Okoye, NC; Gallazzi, FA; Barnes, CL; Cutler, CS; Ketring, AR; Hoffman, TJ; Jurisson, SS

Published Date

  • June 2018

Published In

Volume / Issue

  • 61 /

Start / End Page

  • 1 - 10

PubMed ID

  • 29571038

Electronic International Standard Serial Number (EISSN)

  • 1872-9614

Digital Object Identifier (DOI)

  • 10.1016/j.nucmedbio.2018.03.001


  • eng

Conference Location

  • United States