[11C]MK-4232: Development, Characterization, and Clinical Application of a Novel CGRP Receptor PET Tracer

I. Introduction to [11C]MK-4232

[11C]MK-4232 has emerged as a pivotal radiopharmaceutical, distinguished as the first Positron Emission Tomography (PET) tracer meticulously developed for the in vivo imaging and quantification of the Calcitonin Gene-Related Peptide (CGRP) receptor.[1] This innovation represented a significant advancement in neuropharmacological research, furnishing an unprecedented capability to investigate the CGRP system directly within the complexities of the living human brain. The CGRP system, which includes the CGRP neuropeptide and its specific receptor (CGRP-R), is fundamentally involved in neurovascular regulation and has been robustly implicated in the pathophysiology of migraine headaches.[1] Consequently, the advent of a dedicated PET tracer for the CGRP-R was of paramount importance for enhancing the understanding of migraine's intricate mechanisms and for facilitating the rational design and critical evaluation of novel CGRP-targeted therapeutic interventions.

The capacity to visualize and accurately measure CGRP receptor density and occupancy within the human brain, afforded by [11C]MK-4232, permits direct inquiry into the functional role of central CGRP pathways in migraine. Moreover, it provides a means to assess the degree to which peripherally administered pharmaceutical agents engage their intended central targets, a persistent and critical question in the development of drugs aimed at central nervous system (CNS) disorders.[2][11C]MK-4232 thus serves as an exemplary translational medicine tool, effectively bridging the gap between preclinical discoveries in animal models and their subsequent validation and application in human clinical studies, particularly within the domain of CGRP-R antagonism for migraine therapy.