TY - JOUR T1 - Imaging of the Striatal and Extrastriatal Dopamine Transporter with <sup>18</sup>F-LBT-999: Quantification, Biodistribution, and Radiation Dosimetry in Nonhuman Primates JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1313 LP - 1321 DO - 10.2967/jnumed.111.089953 VL - 52 IS - 8 AU - Andrea Varrone AU - Vladimir Stepanov AU - Ryuji Nakao AU - Miklós Tóth AU - Balázs Gulyás AU - Patrik Emond AU - Jean Bernard Deloye AU - Johnny Vercouillie AU - Michael G. Stabin AU - Cathrine Jonsson AU - Denis Guilloteau AU - Christer Halldin Y1 - 2011/08/01 UR - http://jnm.snmjournals.org/content/52/8/1313.abstract N2 - The aim of this study was to evaluate the quantification, biodistribution, and radiation dosimetry of the novel dopamine transporter (DAT) radioligand 18F-(2S,3S)-methyl 8-((E)-4-fluorobut-2-en-1-yl)-3-(p-tolyl)-8-azabicyclo[3.2.1]octane-2-carboxylate (18F-LBT-999) in nonhuman primates. Methods: The brain study was conducted in 4 female rhesus monkeys. PET measurements were conducted for 243 min using the high-resolution research tomograph (HRRT) with the measurement of the metabolite-corrected arterial input function and protein binding. Quantification was performed with kinetic analysis using 2-tissue- and 1-tissue-compartment models, with Logan graphical analysis and with different reference tissue models. The outcome measures were total distribution volume (VT), nondisplaceable distribution volume (VND), binding potential relative to the free concentration of radioligand in plasma (BPF), and binding potential relative to the concentration of nondisplaceable radioligand in tissue (BPND) = VT − VND/VND using the cerebellum as a reference region. For the biodistribution and radiation dosimetry, 2 female cynomolgus monkeys were studied. Whole-body PET scans were obtained using a PET/CT system for approximately 250 min. Estimates of the absorbed radiation dose in humans were calculated using OLINDA/EXM software. Results: 18F-LBT-999 showed good brain uptake (300% standardized uptake value) and regional distribution according to known DAT density. The 2-tissue-compartment model was the preferred model for the quantification. Late peak equilibrium (120–140 min) and slow washout were observed in the striatum, with high variability of VT, BPF, and BPND. When the different models were compared with the 2-tissue-compartment model, the underestimation of VT or BPND was larger in the caudate and putamen than in the midbrain and thalamus. The reference tissue models were suitable for the quantification. The whole-body distribution study showed that the main routes of excretion of 18F-LBT-999 were the urinary and gastrointestinal systems, with the bladder being the critical organ. Accumulation of 18F-LBT-999 was found in the bone and skull, with a relatively high dose estimated for the osteogenic cells. The range of calculated effective dose was 0.021–0.022 mSv/MBq. Conclusion: 18F-LBT-999 seemed to be a suitable PET radioligand for the DAT quantification, particularly for extrastriatal regions. The skull uptake did not seem to be a limitation for brain imaging. The calculated dosimetry estimates based on data in nonhuman primates seemed comparable with those of other clinically used 18F-labeled radioligands, for example, 18F-FDG (0.024–0.027 mSv/MBq). ER -