The PET radioligand ¹⁸F-FIMX images and quantifies metabotropic glutamate receptor 1 in proportion to the regional density of its gene transcript in human brain

A recent study from our laboratory found that ¹⁸F-FIMX is an excellent PET radioligand for quantifying metabotropic glutamate receptor 1 (mGluR1) in monkey brain. This study evaluated the ability of ¹⁸F-FIMX to quantify mGluR1 in humans. A second goal was to use the relative density of mGluR1 gene transcripts in brain regions to estimate specific uptake and nondisplaceable uptake (VND) in each brain region. Methods: After injection of 189 ± 3 MBq of ¹⁸F-FIMX, 12 healthy volunteers underwent a dynamic PET scan over 120 min. For 6 volunteers, images were acquired until 210 min. A metabolitecorrected arterial input function was measured from the radial artery. Four other subjects underwent whole-body scanning to estimate radiation exposure. Results: ¹⁸F-FIMX uptake into the human brain was high (SUV 5 4-6 in the cerebellum), peaked at about 10 min, and washed out rapidly. An unconstrained 2-tissue-compartment model fitted the data well, and distribution volume (VT) (mL?cm?3) values ranged from 1.5 in the caudate to 11 in the cerebellum. A 120-min scan provided stable VT values in all regions except the cerebellum, for which an acquisition time of at least 170 min was necessary. VT values in brain regions correlated well with mGluR1 transcript density, and the correlation suggested that VND of ¹⁸F-FIMX was quite low (0.5 mL?cm?3). This measure of VND in humans was similar to that from a receptor blocking study in monkeys, after correcting for differences in plasma protein binDing. Similar to other 18F-labeled ligands, the effective dose was about 23 ?Sv/MBq. Conclusion: 18FFIMX can quantify mGluR1 in the human brain with a 120-to 170-min scan. Correlation of brain uptake with the relative density of mGluR1 transcript allows specific receptor binDing of a radioligand to be quantified without injecting pharmacologic doses of a blocking agent.