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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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
Article number67
Pages (from-to)5064−5074
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number6
Publication statusPublished - 28 Mar 2024


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