Florbenazine F18

Our research groups recently described a series of small‐molecule inducers of β‐cell proliferation that could be used to increase β‐cell mass. To mitigate the risk of nonspecific proliferation of other cell types, we devised a delivery strategy built on the tissue specificity observed in the experimental β‐cell imaging agent (+)‐dihydrotetrabenazine (DTBZ). The β‐cell proliferator agent aminopyrazine (AP) was covalently linked with (+)‐DTBZ to afford conjugates that retain both the proliferation activity and binding affinity for vesicular monoamine transporter‐2 (VMAT2). In vivo mouse tissue distribution studies of a prototypical AP–DTBZ conjugate showed 15‐fold pancreas exposure over plasma. Tissue‐to‐plasma ratios in liver and kidneys were two‐ and five‐fold, respectively. This work is the first demonstration of enhanced delivery of β‐cell‐proliferating molecules to the pancreas by leveraging the intrinsic tissue specificity of a β‐cell imaging agent.