TY - JOUR T1 - A constraint kinetic modeling approach to quantify [<sup>11</sup>C]DPA-713 specific binding for PET imaging of neuroinflammation JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 852 LP - 852 VL - 58 IS - supplement 1 AU - Yun Zhou AU - Jennifer Coughlin AU - Yong Du AU - Qian Zhao AU - Lingxia Ha AU - Jeffrey Leal AU - Martin Pomper Y1 - 2017/05/01 UR - http://jnm.snmjournals.org/content/58/supplement_1/852.abstract N2 - 852Objectives: [11C]DPA-713 is a second generation radioligand for PET imaging of neuroinflammation that targets the translocator protein (TSPO). Three genotypes of TSPO dictate binding between high CC (Ala147/Ala147), intermediate or mixed CT (Ala147/Thr147), and low TT (Thr147/Thr147) binders, respectively. It remains challenging to estimate [11C]DPA-713 specific binding due to lack of a true reference tissue. The objective of this study is to evaluate a physiological-constraint compartmental modeling approach for estimation of specific binding (BPND) in [11C]DPA-713 dynamic PET study.Methods: A standard sequential two-tissue compartment model, free plus nonspecific binding and specific binding compartments, with dynamic PET and plasma input was used to quantify [11C]DPA-713 nonspecific and specific binding. Thirty-one human (17 CC, 21 CT, and 3 TT) dynamic brain PET scans with metabolite-corrected plasma input function were collected. Regions of interest (ROIs) were manually drawn on co-registered structural MRIs. A constraint of same free-plus-nonspecific distribution volume (VND) and rate constant from specific binding to free-plus-nonspecific binding compartment (k4) (2-scan constraint) were applied to all ROIs of all subjects in sub-the populations (n=10) sampled from the 31 subjects. The effect of sub-population sample size on the estimates from the constraint kinetic modeling approach was also investigated.Results: Estimates of VND and k4 were 0.65 ± 0.13 and 0.13 ± 0.01(mean ± SD), respectively. The BPNDs for CC, CT and TT are shown in the Figure, where caudate had lowest BPND. There were no significant simple size effects in the total distribution volume VT and BPND estimates.Conclusion: It is feasible to estimate [11C]DPA-713 specific binding by applying the constraint kinetic modeling approach to the population including individuals of genotypes of CC, CT , and TT. To develop non-invasive kinetic approach (without blood sampling) from the study for quantification of [11C]DPA-713 specific binding is under investigation. Research Support: $$graphic_BCE07C55-ED2A-4A94-92B2-10EAE7DC76D1$$ ER -