super( 18)F-Alfatide II and super( 18)F-FDG Dual-Tracer Dynamic PET for Parametric, Early Prediction of Tumor Response to Therapy

A single dynamic PET acquisition using multiple tracers administered closely in time could provide valuable complementary information about a tumor's status under quasiconstant conditions. This study aimed to investigate the utility of dual-tracer dynamic PET imaging with super( 18)F-alfatide II ( super( 18)F-AlF-NOTA-E[PEGz sub( 4)-c(RGDfk)] sub( 2)) and super( 18)F-FDG for parametric monitoring of tumor responses to therapy. We administered doxorubicin to one group of athymic nude mice with U87MG tumors and paclitaxel protein-bound particles to another group of mice with MDA-MB-435 tumors. To monitor therapeutic responses, we performed dual-tracer dynamic imaging, in sessions that lasted 90 min, starting with injection via the tail vein catheters with super( 18)F-alfatide II, followed 40 min later by super( 18)F-FDG. To achieve signal separation of the 2 tracers, we fit a 3-compartment reversible model to the time-activity curve of super( 18)F-alfatide II for the 40 min before super( 18)F-FDG injection and then extrapolated to 90 min. The super( 18)F-FDG tumor time-activity curve was isolated from the 90-min dual-tracer tumor time-activity curve by subtracting the fitted super( 18)F-alfatide II tumor time-activity curve. With separated tumor time-activity curves, the super( 18)F-alfatide II binding potential (Bp = k3/k4) and volume of distribution (VD) and super( 18)F-FDG influx rate ((K1 x k3)/(k2 + k3)) based on the Patlak method were calculated to validate the signal recovery in a comparison with 60-min single-tracer imaging and to monitor therapeutic response. The transport and binding rate parameters K1-k3 of super( 18)F-alfatide II, calculated from the first 40 min of the dual-tracer dynamic scan, as well as Bp and V sub( D) correlated well with the parameters from the 60-min single-tracer scan (R super( 2) 0.95). Compared with the results of single-tracer PET imaging, super( 18)F-FDG tumor uptake and influx were recovered well from dual-tracer imaging. On doxorubicin treatment, whereas no significant changes in static tracer uptake values of super( 18)F-alfatide II or super( 18)F-FDG were observed, both super( 18)F-alfatide II Bp and super( 18)F-FDG influx from kinetic analysis in tumors showed significant decreases. For therapy of MDA-MB-435 tumors with paclitaxel protein-bound particles, a significant decrease was observed only with super( 18)F-alfatide II Bp value from kinetic analysis but not super( 18)F-FDG influx. The parameters fitted with