Modified Reaction Conditions for the Radiosynthesis of ¹¹C‑Labeled Asymmetrical Guanidines and the Automated...

Radiolabeled guanidines such as ^123/131I-labeled meta-iodobenzylguanidine (mIBG) have been widely used in nuclear medicine for imaging of cardiac sympathetic nerves, as well as imaging and treatment of neuroendocrine tumors. For a variety of reasons (e.g., low tumor uptake, suboptimal kinetics), there is a need for second generation guanidines, and the synthesis and evaluation of such radiopharmaceuticals is a long-standing focus of our group. However, to date, the generation of analogues has been limited to other monosubstituted guanidines, while both symmetrical and asymmetrical disubstituted analogues around the guanidine have been largely ignored because of their synthetic challenges. To address this limitation, herein we report general conditions for the synthesis of carbon-11 radiolabeled asymmetric guanidines and show proof-of-concept through the automated radiosynthesis and preclinical evaluation of a novel mIBG analogue.