A New, Second Generation Trithiol Bifunctional Chelate for 72,77 As: Trithiol(b)-(Ser) 2 -RM2

• Published in: Bioconjugate chemistry 2021-07, Vol.32 (7), p.1364-1373
• Main Authors: Najafi Khosroshahi, Firouzeh, Feng, Yutian, Ma, Li, Manring, Simon, Rold, Tammy L, Gallazzi, Fabio A, Kelley, Steven P, Embree, Mary F, Hennkens, Heather M, Hoffman, Timothy J, Jurisson, Silvia S
• Format: Article
• Language: English
• Subjects: Animals; Arsenic - chemistry; Biochemistry & Molecular Biology; Chelating Agents - chemistry; Chelating Agents - pharmacokinetics; Chemistry; Humans; Inhibitory Concentration 50; Ligands; Male; Mice; PC-3 Cells; Positron-Emission Tomography - methods; Precision Medicine; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Receptors, Bombesin - chemistry; Sulfhydryl Compounds - chemistry; Tissue Distribution
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.0c00658

Trithiol chelates are suitable for labeling radioarsenic ( As: 2.49 MeV β , 26 h; As: 0.683 MeV β , 38.8 h) to form potential theranostic radiopharmaceuticals for positron emission tomography (PET) imaging and therapy. A trithiol(b)-(Ser) -RM2 bioconjugate and its arsenic complex were synthesized and characterized. The trithiol(b)-(Ser) -RM2 bioconjugate was radiolabeled with no-carrier-added As in over 95% radiochemical yield and was stable for over 48 h, and IC cell binding studies of [ As]As-trithiol(b)-(Ser) -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-trithiol(b)-(Ser) -RM2 demonstrating both pancreatic uptake and hepatobiliary clearance.