[18F]FIMX is a promising tracer to quantify metabotropic glutamate receptor 1 (mGluR1) in human brain

Objectives The metabotropic glutamate receptor 1 (mGluR1) may play a role in several neuropsychiatric disorders. Therefore a radioligand for mGluR1 would be useful to study the potential pathophysiological role of this receptor and may also facilitate therapeutic drug development aimed at this target. We recently reported that the novel radioligand [18F]FIMX provides excellent imaging of mGluR1 in monkey brain, showing high uptake, appropriate regional distribution (i.e., especially high in cerebellum), fast washout, and high receptor-specific signal. We present here preliminary PET imaging results in humans

Methods To date, three healthy volunteers have been injected with [18F]FIMX. The first was imaged for two hours from head to mid-thigh to estimate the biodistribution of the radioligand. The other two had a two-hour dynamic brain PET scan with arterial input function to perform kinetic modeling

Results All subjects had regional radioactivity distributions in brain reflecting that expected for mGluR1. The cerebellum had highest uptake (3 SUV at 15 min, decreasing to 1.8 at 120 min), whereas the uptake in other cortical regions with low density of mGluR1 ranged from 0.3 to 1 SUV at 120 min. Initial kinetic modeling with arterial input function suggests the data are well fit with a two-compartment model. VT (mL/cm3) in cerebellum was ~ 5, whereas that in caudate was ~ 1.3. Plasma free fraction was about 0.7%. The whole body images showed a high and accumulating activity in bowel and bladder, suggesting substantial fecal and urinary excretion routes. Uptake of radioactivity in skull appears absent.

Conclusions As in monkey, [18F]FIMX shows promising characteristics for quantify mGluR1 in humans, based on initial results from three subjects