The positron emission tomographic 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 positron emission tomography (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 (VS) 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 minutes. In six of them, images were acquired until 210 minutes. A metabolite-corrected arterial input function was measured from the radial artery. Four other subjects had whole-body scans to estimate radiation exposure. Results: ¹⁸F-FIMX uptake into human brain was high (SUV = 4-6 in cerebellum), peaked at about 10 minutes, and washed out rapidly. An unconstrained two-tissue compartment model fitted the data well, and distribution volume (VT) (mL • cm-3) values ranged from 1.5 in caudate to 11 in cerebellum. A 120-minute scan provided stable VT values in all regions except the cerebellum, for which an acquisition time of at least 170 minutes 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 very 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 µSv/MBq. Conclusion: ¹⁸F-FIMX can quantify mGluR1 in human brain with a 120 – 170 minute scan. Correlation of brain uptake with the relative density of mGluR1 transcript allows specific receptor binding of a radioligand to be quantified without injecting pharmacological doses of a blocking agent.

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