Microdose PET for the metabotropic glutamate receptor type 5 (mGluR5)

1774 Objectives: bjectives A key component of an ambulatory microdose positron-emission tomography (AM-PET) system (Kinahan, et al.J Nucl Med. 2015;56 (supplement 3):1540) is the administration of a radiotracer dose markedly less than the standard dose. The reduced radiation exposure of an AM-PET systems would facilitate the use of the procedure to monitor diagnostic and therapeutic interventions for disorders requiring multiple sequential assessments [Melroy, et al.Sensors (Basel). 2017;17(5). pii: E1164]. Usable images have been obtained with radioactivity doses a quarter those of standard scans [Bauer. et al. Brain Behav. 2016;6:e00530]. We examined the usability of a scan of a participant who received one tenth the standard radio tracer dose. Methods A 20-year-old woman with autism was administered 20.72 MBq (0.56 mCi) [18F]-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([18F]FPEB), a radiotracer to measure mGluR5 expression (Wong, et al.J Nucl Med. 2013;54, 388-396), with specific activity of 77.8 GBq/micromole (2.1 Ci/micromole), a mass of 0.06 mcg, and a mass dose of 0.93 pg/kg, followed by 90 minutes of PET on a high resolution research tomograph (HRRT). A transmission scan was conducted for six minutes before the emission scan to correct for attenuation. The nondisplaceable binding potential (BPND) of [18F]FPEB was obtained to measure the density of unoccupied receptors (Bmax9) in various regions of the brain. Volumes of interest (VOIs) were obtained automatically, and refined manually as needed. The cerebellar white matter was employed for the reference region since this structure demonstrated negligible densities of mGluR5s. Then, VOIs were transferred from MRI to PET space according to MRI-to-PET coregistration parameters, and applied to PET frames to obtain regional time (radioactivity) curves. Regional BPNDs were obtained by reference tissue graphical analysis and the multilinear reference tissue method with two parameters. The data from the female participant with autism who received a microdose of 20.72 MBq (0.56 mCi) [18F]FPEB were compared and contrasted with the data of 11 healthy men aged 42 + 7 years given an average dose (+SD) of 181 + 14 MBq (4.90 + 0.38 mCi), with specific activity of 370 + 230 GBq/micromole (10 + 6.22 Ci/micromole), a mass of 0.15 + 0.10 mcg, and a mass dose of 1.8 + 1.3 pg/kg (Wong, et al., 2013). Results See Table for nondisplaceable binding potentials (BPNDs) of regions of the brain after the intravenous administration of 20.72 MBq (n=1) and 181 + 14 MBq (n=11) [18F]FPEB (Wong, et al., 2013). The higher BPNDs in the frontal lobe and the striatum of the woman likely reflect an excitatory/inhibitory imbalance characteristic of autism (Hwang, et al.Int Rev Psychiatry. 2017;29:530-554). The variability of BPNDs likely reflect the variability of the measurements of the healthy men (Wong, et al., 2013) and the small sample sizes. The Table indicates that the measurements for the microdose and the standard dose are comparable for the key regions including the frontal lobe and the striatum. Conclusions Microdoses as low as a tenth of the radioactivity of the standard doses of [18F]FPEB generate images that are comparable to those of standard doses. Microdoses administered to participants who refrain from head movement during scrupulously conducted scans can generate images that are comparable to those of standard doses. This suggests that the use of microdoses of a tenth the standard dose of [18F] radiotracers may be suitable for AM-PET techniques. Furthermore, microdoses of [18F] radiotracers may be appropriate for pediatric and other vulnerable populations who require multiple PET scans for diagnostic and therapeutic purposes. To avoid unnecessary radiation exposure to patients, microdoses of [18F] radiotracers may be optimal for nuclear medicine procedures. Research support The Winston and Maxine Wallin Neuroscience Discovery Fund and NIH grants R33 MH66623P and K24DA000412 and by NIBIB, NIDA, NIAAA 5T32EB006351-05.