Synthesis and preclinical evaluation of a novel 2-[18F]fluoropyridine-bearing rhodamine for myocardial perfusion imaging with PET
- 1McMaster University, Department of Chemistry and Chemical Biology Hamilton ON L8S 4M1 Canada
- 2Brain Health Imaging Centre, Centre for Addiction and Mental Health Toronto ON M5T 1R8 Canada
- 3Department of Psychiatry, University of Toronto Toronto ON M5T1R8 Canada
Abstract
[18F]Rho6G-DEG-F is a rhodamine-based PET radiotracer for myocardial perfusion imaging (MPI) that exhibits excellent first-pass myocardial extraction, persistent cardiac retention, and high heart : liver ratios in rats and pigs. However, in human volunteers, heart : liver contrast was suboptimal. The primary goals of this study were to design an [18F]Rho6G-DEG-F analogue of attenuated lipophilicity for radiolabelling via nucleophilic heteroaromatic 18F-fluorination ([18F]Rho6G-DEG-Py-F; [18F]6), and to evaluate [18F]6 in rats and mice. To that end, precursors bearing 2-nitro- (5) and 2-trimethylammonium triflate (8)- pyridine groups were prepared in overall yields of 48% and 29%, starting from rhodamine 6G; final purification did not require C18 chromatography. Manual standard radiofluorination conditions (TEA[18F]F/TEAHCO3/DMSO/160 °C/20 min) afforded a best decay-corrected radiochemical yield (DC-RCY) of 31% from 5 and 7% from 8. In the latter case, precursor and radiotracer were easily separated by HPLC (molar activity = 33 ± 8 GBq per µmol). Upon translation to an automated synthesizer, [18F]6 was obtained in DC-RCYs of 9.3% and 0.7% from 5 and 8 respectively; best molar activities were 50 and 144 GBq per µmol respectively. [18F]Rho6G-DEG-Py-F exhibited complete stability in rat and mouse serum over 120 min (37 °C). A radiometabolite assay in two rats showed differing metabolic profiles between sexes, but similar % intact tracer at 60 min (32–34%). Micro-PET imaging in rats demonstrated extended myocardial retention (SUV > 1.0 at 120 min), gradual liver washout, and high heart : liver ratios (3.7 in male, 2.5 in female at 120 min); however, similar experiments in mice revealed low heart uptake and rapid metabolism (SUV ∼ 0.3; heart : liver ratio = 1.0 at 120 min).
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BibTeX
@article{mahmood2026synthesis,
title = {{Synthesis and preclinical evaluation of a novel 2-[18F]fluoropyridine-bearing rhodamine for myocardial perfusion imaging with PET}},
author = {Maya Mahmood and Emily Murrell and Seniha Ozyuncu and Junchao Tong and Angelina Lui and James A. H. Inkster},
journal = {RSC Advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra08884h},
url = {https://doi.org/10.1039/d6ra08884h},
note = {CC BY 3.0},
}
RIS
TY - JOUR
TI - Synthesis and preclinical evaluation of a novel 2-[18F]fluoropyridine-bearing rhodamine for myocardial perfusion imaging with PET
AU - Maya Mahmood
AU - Emily Murrell
AU - Seniha Ozyuncu
AU - Junchao Tong
AU - Angelina Lui
AU - James A. H. Inkster
PY - 2026
DA - 2026/11/05
JO - RSC Advances
DO - 10.1039/d6ra08884h
UR - https://doi.org/10.1039/d6ra08884h
AB - [18F]Rho6G-DEG-F is a rhodamine-based PET radiotracer for myocardial perfusion imaging (MPI) that exhibits excellent first-pass myocardial extraction, persistent cardiac retention, and high heart : liver ratios in rats and pigs. However, in human volunteers, heart : liver contrast was suboptimal. The primary goals of this study were to design an [18F]Rho6G-DEG-F analogue of attenuated lipophilicity for radiolabelling via nucleophilic heteroaromatic 18F-fluorination ([18F]Rho6G-DEG-Py-F; [18F]6), and to evaluate [18F]6 in rats and mice. To that end, precursors bearing 2-nitro- (5) and 2-trimethylammonium triflate (8)- pyridine groups were prepared in overall yields of 48% and 29%, starting from rhodamine 6G; final purification did not require C18 chromatography. Manual standard radiofluorination conditions (TEA[18F]F/TEAHCO3/DMSO/160 °C/20 min) afforded a best decay-corrected radiochemical yield (DC-RCY) of 31% from 5 and 7% from 8. In the latter case, precursor and radiotracer were easily separated by HPLC (molar activity = 33 ± 8 GBq per µmol). Upon translation to an automated synthesizer, [18F]6 was obtained in DC-RCYs of 9.3% and 0.7% from 5 and 8 respectively; best molar activities were 50 and 144 GBq per µmol respectively. [18F]Rho6G-DEG-Py-F exhibited complete stability in rat and mouse serum over 120 min (37 °C). A radiometabolite assay in two rats showed differing metabolic profiles between sexes, but similar % intact tracer at 60 min (32–34%). Micro-PET imaging in rats demonstrated extended myocardial retention (SUV > 1.0 at 120 min), gradual liver washout, and high heart : liver ratios (3.7 in male, 2.5 in female at 120 min); however, similar experiments in mice revealed low heart uptake and rapid metabolism (SUV ∼ 0.3; heart : liver ratio = 1.0 at 120 min).
SN - 2046-2069
ER -