TY - JOUR
T1 - Arginine-Selective Bioconjugation Reagent for Effective 18F-labeling of Native Proteins
AU - Sadasivam, Pragalath
AU - Khanapur, Shivashankar
AU - Hartimath, Siddesh V.
AU - Ramasamy, Boominathan
AU - Cheng, Peter
AU - Feng, Chin Zan
AU - Green, David
AU - Davis, Christopher
AU - Goggi, Julian L.
AU - Robins, Edward G.
AU - Yan, Ran
N1 - Funding Information:
P.S. acknowledges funding from the Centre for Doctoral Studies, King’s College London. C.D. acknowledges funding from the EPSRC Ph.D. studentship (EP/R513064/1). The research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, the Wellcome/EPSRC Centre for Medical Engineering at King’s College London [WT203148/Z/16/Z], the King’s College London and UCL Comprehensive Cancer Imaging Centre funded by CRUK and EPSRC in association with the MRC and DoH (England), the Experimental Cancer Medicine Centre at King’s College and the King’s Health Partners/King’s College London Cancer Research UK Cancer Centre. This work was also supported by EPSRC Programme Grant [EP/S032789/1].
Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society
PY - 2024/3/28
Y1 - 2024/3/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85187723851&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.4c00154
DO - 10.1021/acs.jmedchem.4c00154
M3 - Article
AN - SCOPUS:85187723851
SN - 0022-2623
VL - 67
SP - 5064−5074
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 6
M1 - 67
ER -