18F-F13640 PET imaging of functional receptors in humans

Abstract

The vast majority of PET radiopharmaceuticals used for receptor neuroimaging are antagonists. This is particularly true for 5-HT1A receptor radiopharmaceuticals such as F-MPPF or C-WAY100635. These radiolabeled antagonists allow PET neuroimaging of the total pool of receptors, regardless of their functional state. In contrast, agonists bind preferentially to the functionally active state of receptors, a pharmacological property that has not yet been exploited for PET imaging of functional 5-HT1A receptors [1]. To this end, we have developed a highly selective 5-HT1A receptor agonist, FF13640, and validated it in animal models [2]. A postmortem study in Alzheimer subjects showed that the in vitro binding of F-F13640 differs from that of F-MPPF, the prototypical radiopharmaceutical [3]. Here we show the first human brain image obtained in vivo with F-F13640 (study registration, EudraCT 2017-002722-21). A summed brain PET image was obtained in a 32-year-old healthy man after IV injection of the radiopharmaceutical (90-min scan). F-F13640 brain distribution, expressed by the standardized uptake value with the body weight (SUV bw), showed a binding pattern different from that seen with conventional antagonist 5-HT1A radiopharmaceuticals. Although the binding regions are well correlated to the density of 5-HT1A receptors, the ROIs are mainly cortical, indicating that these brain regions are enriched in functionally active receptors. F-F13640 is the first radiopharmaceutical that enables in vivo investigation of functional 5-HT1A receptors that are likely to be altered in pathological conditions such as neurodegenerative diseases or psychiatric disorders. The development of this agonist PET radiopharmaceutical opens new opportunities for nuclear medicine.