Introduction: Due to its involvement in a variety of pathologies (obesity, diabetes, gut inflammation and depression), the melanin concentrating hormone receptor 1 (MCHR1) is a new target for the treatment of these lifestyle diseases. We previously presented the radiosynthesis of [(11)C]SNAP-7941, the first potential PET tracer for the MCHR1.
Methods: We herein present its in vitro and in vivo evaluation, including binding affinity, plasma stability, stability against liver mircrosomes and carboxylesterase, lipohilicity, biodistribution, in vivo metabolism and small-animal PET.
Results: [(11)C]SNAP-7941 evinced high stability against liver microsomes, carboxylesterase and in human plasma. The first small-animal PET experiments revealed a 5 fold increased brain uptake after Pgp/BCRP inhibition. Therefore, it can be assumed that [(11)C]SNAP-7941 is a Pgp/BCRP substrate. No metabolites were found in brain.
Conclusion: On the basis of these experiments with healthy rats, the suitability of [(11)C]SNAP-7941 for the visualisation of central and peripheral MCHR1 remains speculative.
Keywords: MCHR1; Metabolites; PET; SNAP-7941.
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