Quantitative Analysis and Comparison Study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 Using a Reference Tissue Model

With favorable pharmacokinetics and binding affinity for alpha(v)beta(3) integrin, F-18-labeled dimeric cyclic RGD peptide ([F-18]FPPRGD2) has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an F-18-fluoride-aluminum complex labeled RGD tracer ([F-18]AlF-NOTA-PRGD2), provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare Ga-68-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin alpha(v)beta(3). The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [F-18]FPPRGD2, [F-18]AlF-NOTA-PRGD2, and [Ga-68]Ga-NOTA-PRGD2. U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the injection of three tracers. Kinetic parameters were calculated using Logan graphical analysis with reference tissue. Parametric maps were generated using voxel-level modeling. All three compounds showed high binding potential (Bp(ND) = k(3)/k(4)) in tumor voxels. [F-18]AlF-NOTA-PRGD2 showed comparable Bp(ND) value (3.75 +/- 0.65) with those of [F-18]FPPRGD2 (3.39 +/- 0.84) and [Ga-68]Ga-NOTA-PRGD2 (3.09 +/- 0.21) (p > 0.05). Little difference was found in volume of distribution (V-T) among these three RGD tracers in tumor, liver and muscle. Parametric maps showed similar kinetic parameters for all three tracers. We also demonstrated that the impact of non-specific binding could be eliminated in the kinetic analysis. Consequently, kinetic parameter estimation showed more comparable results among groups than static image analysis. In conclusion, [F-18]AlF-NOTA-PRGD2 and [Ga-68]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [F-18]FPPRGD2. Despite the apparent difference in tumor uptake (%ID/g determined from static images) and clearance pattern, the actual specific binding component extrapolated from kinetic modeling appears to be comparable for all three dimeric RGD tracers.