RT Journal Article SR Electronic T1 Optimized Quantification of Translocator Protein Radioligand 18F-DPA-714 Uptake in the Brain of Genotyped Healthy Volunteers JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1048 OP 1054 DO 10.2967/jnumed.115.156083 VO 56 IS 7 A1 Sonia Lavisse A1 Daniel García-Lorenzo A1 Marie-Anne Peyronneau A1 Benedetta Bodini A1 Claire Thiriez A1 Bertrand Kuhnast A1 Claude Comtat A1 Philippe Remy A1 Bruno Stankoff A1 Michel Bottlaender YR 2015 UL http://jnm.snmjournals.org/content/56/7/1048.abstract AB Translocator protein (TSPO) is expressed at a low level in healthy brain and is upregulated during inflammatory processes that may occur in neurodegenerative diseases. Thus, TSPO may be a suitable in vivo indicator of neurodegeneration. Here, we quantified the 18F-DPA-714 radioligand in healthy TSPO-genotyped volunteers and developed a method to eliminate the need for invasive arterial blood sampling. Methods: Ten controls (7 high-affinity binders [HABs] and 3 mixed-affinity binders [MABs]) underwent 18F-DPA-714 PET with arterial and venous sampling. 18F-DPA-714 binding was quantified with a metabolite-corrected arterial plasma input function, using the 1- and 2-tissue-compartment models (TCMs) as well as the Logan analysis to estimate total volume distribution (VT) in the regions of interest. Alternative quantification methods were tested, including tissue-to-plasma ratio or population-based input function approaches normalized by late time points of arterial or venous samples. Results: The distribution pattern of 18F-DPA-714 was consistent with the known distribution of TSPO in humans, with the thalamus displaying the highest binding and the cerebellum the lowest. The 2-TCM best described the regional kinetics of 18F-DPA-714 in the brain, with good identifiability (percentage coefficient of variation < 5%). For each region of interest, VT was 47.6% ± 6.3% higher in HABs than in MABs, and estimates from the 2-TCM and the Logan analyses were highly correlated. Equilibrium was reached at 60 min after injection. VT calculated with alternative methods using arterial samples was strongly and significantly correlated with that calculated by the 2-TCM. Replacement of arterial with venous sampling in these methods led to a significant but lower correlation. Conclusion: Genotyping of subjects is a prerequisite for a reliable quantification of 18F-DPA-714 PET images. The 2-TCM and the Logan analyses are accurate methods to estimate 18F-DPA-714 VT in the human brain of both HAB and MAB individuals. Population-based input function and tissue-to-plasma ratio with a single arterial sample are promising alternatives to classic arterial plasma input function. Substitution with venous samples is promising but still requires methodologic improvements.