posted on 2020-10-05, 13:39authored byAustin
Y. Zhao, Allen F. Brooks, David M. Raffel, Jenelle Stauff, Janna Arteaga, Peter J. H. Scott, Xia Shao
Radiolabeled
guanidines such as meta-iodobenzylguanidine
(MIBG) find utility in nuclear medicine as both diagnostic imaging
agents and radiotherapeutics and, over the years, numerous methods
for incorporating radionuclides into guanidines have been developed.
In connection with a project developing new positron emission tomography
(PET) radiotracers for cardiac sympathetic nerve density, we had cause
to prepare [11C]3F-PHPOG. However, it quickly became apparent
that radiolabeling of guanidine scaffolds with carbon-11 has remained
challenging, and historical methods lack compatibility with modern
automated radiochemistry synthesis platforms and current Good Manufacturing
Practice (cGMP) requirements. To address this challenge, we report
a new automated method for radiolabeling guanidines with carbon-11.
The method was used to prepare a series of [11C]guanidines
in good radiochemical yield (8–76% by radio-HPLC) and was found
to have broad substrate scope and tolerance of unprotected OH and
NH functional groups. The method was used to synthesize [11C]3F-PHPOG for preclinical imaging, and suitability of the radiotracer
for preclinical use was demonstrated through preliminary cardiac PET
in New Zealand white rabbits which revealed good cardiac uptake and
expected retention in the heart.