%0 Journal Article %A Anthony J Young %A Austin R Pantel %A Varsha Viswanath %A Tiffany L Dominguez %A Mehran Makvandi %A Hsiaoju Lee %A Shihong Li %A Erin K Schubert %A Daniel A Pryma %A Michael D Farwell %A Robert H Mach %A Fiona Simpkins %A Lilie L Lin %A David A Mankoff %A Robert K Doot %T Kinetic and static analysis of poly-(adenosine diphosphate-ribose) polymerase-1 (PARP-1) targeted 18F-FluorThanatrace (18F-FTT) PET images of ovarian cancer %D 2021 %R 10.2967/jnumed.121.261894 %J Journal of Nuclear Medicine %P jnumed.121.261894 %X The poly-(adenosine diphosphate-ribose) polymerase (PARP) family of proteins participates in numerous functions, most notably the DNA damage response. Cancer vulnerability to DNA damage has led to development of several PARP inhibitors (PARPi). This class of drugs has demonstrated therapeutic efficacy in ovarian, breast, and prostate cancers, but with variable response. Consequently, clinics need to select patients likely to benefit from these targeted therapies. In vivo imaging of 18F-FluorThanatrace (18F-FTT) uptake has been shown to correspond to PARP-1 expression in tissue. This study characterizes the pharmacokinetics of 18F-FTT and tests kinetic and static models to guide metric selection in future studies assessing 18F-FTT as a biomarker of response to PARPi therapy. Methods: Fourteen prospectively enrolled ovarian cancer patients were injected with 18F-FTT and imaged dynamically for 60-minutes post-injection followed by up to two whole-body scans, with venous blood activity and metabolite measurements. Maximum and peak standardized uptake values (SUVmax and SUVpeak) were extracted from dynamic images and whole-body scans. Kinetic parameter estimates and SUVs were assessed for correlations with tissue PARP-1 immunofluorescence (n = 7). Simulations of population kinetic parameters enabled estimation of measurement bias and precision in parameter estimates. Results: 18F-FTT blood clearance was variable, but labeled metabolite profiles were similar across patients, supporting use of a population parent fraction curve. Total distribution volume (VT) from a reversible two-tissue compartment model and Logan reference tissue distribution volume ratio (Logan DVR) from the first hour of PET acquisition correlated with tumor PARP-1 expression by immunofluorescence (r=0.76 and 0.83 respectively, p<0.05). DVR bias and precision estimates were 6.4% and 29.1%, respectively. SUVmax and SUVpeak acquired from images with midpoints of 57.5, 110±3, and 199±4 min highly correlated with PARP-1 expression (mean±standard deviation, r≥0.79, p<0.05). Conclusion: Tumor SUVmax and SUVpeak at 55-60 minutes post-injection and later and DVR from ≥ 60-minutes appear to be robust non-invasive measures of PARP-1 binding. 18F-FTT uptake in ovarian cancer was best described by models of reversible binding. However, pharmacokinetic patterns of tracer uptake were somewhat variable, especially at later time points. %U https://jnm.snmjournals.org/content/jnumed/early/2021/04/15/jnumed.121.261894.full.pdf