Design and Preclinical Evaluation of 18F-Labeled Phenoxyalkylguanidines as Novel Norepinephrine Transporter Radiotracers for Myocardial and Tumor Imaging.
Y, W., M, H., L, P., Y, X., Y, Z., C, Z., K, L., Y, C., M, L., & H, Y. (2026). Design and Preclinical Evaluation of 18F-Labeled Phenoxyalkylguanidines as Novel Norepinephrine Transporter Radiotracers for Myocardial and Tumor Imaging.. Journal of medicinal chemistry. https://doi.org/10.1021/acs.jmedchem.6c02005
Y W, M H, L P, Y X, Y Z, C Z, et al. Design and Preclinical Evaluation of 18F-Labeled Phenoxyalkylguanidines as Novel Norepinephrine Transporter Radiotracers for Myocardial and Tumor Imaging.. Journal of medicinal chemistry. 2026; doi: 10.1021/acs.jmedchem.6c02005
Y W, M H, L P, et al. Design and Preclinical Evaluation of 18F-Labeled Phenoxyalkylguanidines as Novel Norepinephrine Transporter Radiotracers for Myocardial and Tumor Imaging.[J]. Journal of medicinal chemistry. 2026. DOI: 10.1021/acs.jmedchem.6c02005.
@article{y2026,
author = {Wang Y and Hu M and Pan L and Xie Y and Zou Y and Zheng C and Lu K and Cao Y and Li M and Yin H},
title = {Design and Preclinical Evaluation of 18F-Labeled Phenoxyalkylguanidines as Novel Norepinephrine Transporter Radiotracers for Myocardial and Tumor Imaging.},
journal = {Journal of medicinal chemistry},
year = {2026},
doi = {10.1021/acs.jmedchem.6c02005},
note = {PMID: 42593933},
}
TY - JOUR AU - Wang Y AU - Hu M AU - Pan L AU - Xie Y AU - Zou Y AU - Zheng C AU - Lu K AU - Cao Y AU - Li M AU - Yin H TI - Design and Preclinical Evaluation of 18F-Labeled Phenoxyalkylguanidines as Novel Norepinephrine Transporter Radiotracers for Myocardial and Tumor Imaging. T2 - Journal of medicinal chemistry PY - 2026 DO - 10.1021/acs.jmedchem.6c02005 AN - PMID:42593933 ER -
The norepinephrine transporter (NET) is a key target for PET imaging of sympathetic nerves and neuroendocrine tumors. Herein, we developed a series of novel aryl 18F-labeled phenoxyalkylguanidine PET tracers with optimized alkoxy chains to improve NET-binding affinity, metabolic stability, and imaging performance. The tracers were readily synthesized by photocatalyzed 18F-fluorination. The lead compound, [18F] o FPhOEG, exhibited high radiochemical conversion (82.8%), favorable lipophilicity (logD = -0.39), and potent NET affinity (IC50 = 0.097 μM). In vivo studies demonstrated high and sustained target uptake (myocardial SUVmax = 8.95 in rats; tumor SUVmax = 23.35 in mice) and rapid hepatic clearance, resulting in heart-to-liver and tumor-to-liver ratios approximately 3-fold higher than those of the clinically used [18F] m FBG. Moreover, [18F] o FPhOEG was successfully produced on a commercial automated synthesizer from a readily available precursor, highlighting its promise for clinical translation in cardiac and oncological PET imaging.