Arginine-Selective Bioconjugation Reagent for Effective 18F-labeling of Native Proteins

Pragalath Sadasivam, Shivashankar Khanapur, Siddesh V. Hartimath, Boominathan Ramasamy, Peter Cheng, Chin Zan Feng, David Green, Christopher Davis, Julian L. Goggi, Edward G. Robins, Ran Yan

Research output: Contribution to journalArticlepeer-review

Abstract

Protein-based 18F-PET tracers offer new possibilities in early disease detection and personalized medicine. Their development relies heavily on the availability and effectiveness of 18F-prosthetic groups. We prepared and evaluated a novel arginine-selective prosthetic group, 4-[18F]fluorophenylglyoxal ([18F]FPG). [18F]FPG was radiosynthesized by a one-pot, two-step procedure with a non-decay-corrected (n.d.c.) isolated radiochemical yield (RCY) of 41 ± 8% (n = 10). [18F]FPG constitutes a generic tool for 18F-labeling of various proteins, including human serum albumin (HSA), ubiquitin, interleukin-2, and interleukin-4 in ∼30-60% n.d.c. isolated RCYs. [18F]FPG conjugation with arginine residues is highly selective, even in the presence of a large excess of lysine, cysteine, and histidine. [18F]FPG protein conjugates are able to preserve the binding affinity of the native proteins while also demonstrating excellent in vivo stability. The [18F]FPG-HSA conjugate has prolonged blood retention, which can be applied as a potential blood pool PET imaging agent. Thus, [18F]FPG is an arginine-selective bioconjugation reagent that can be effectively used for the development of 18F-labeled protein radiopharmaceuticals.

Original languageEnglish
JournalJournal of medicinal chemistry
DOIs
Publication statusAccepted/In press - 2024

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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