Quantitative analysis and comparison study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 using a reference tissue model

PLoS One. 2012;7(5):e37506. doi: 10.1371/journal.pone.0037506. Epub 2012 May 18.


With favorable pharmacokinetics and binding affinity for α(v)β(3) integrin, (18)F-labeled dimeric cyclic RGD peptide ([(18)F]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 (18)F-fluoride-aluminum complex labeled RGD tracer ([(18)F]AlF-NOTA-PRGD2), provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare (68)Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin α(v)β(3). The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [(18)F]FPPRGD2, [(18)F]AlF-NOTA-PRGD2, and [(68)Ga]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. [(18)F]AlF-NOTA-PRGD2 showed comparable Bp(ND) value (3.75±0.65) with those of [(18)F]FPPRGD2 (3.39±0.84) and [(68)Ga]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, [(18)F]AlF-NOTA-PRGD2 and [(68)Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [(18)F]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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Compounds / metabolism*
  • Animals
  • Fluorides / metabolism*
  • Gallium Radioisotopes / metabolism*
  • Heterocyclic Compounds / metabolism*
  • Heterocyclic Compounds, 1-Ring
  • Integrin alphaVbeta3 / metabolism
  • Mice
  • Models, Chemical
  • Molecular Probes / metabolism
  • Molecular Probes / pharmacokinetics*
  • Organophosphonates / metabolism
  • Organophosphonates / pharmacokinetics*
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacokinetics*
  • Positron-Emission Tomography
  • Radioactive Tracers


  • Aluminum Compounds
  • Gallium Radioisotopes
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • Integrin alphaVbeta3
  • Molecular Probes
  • Organophosphonates
  • Peptides, Cyclic
  • RGD-2 compound
  • Radioactive Tracers
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • Fluorides