(18)F-FPPRGD2, which was approved for clinical study recently, has favorable properties for integrin targeting and showed potential for antiangiogenic therapy and early response monitoring. However, the time-consuming multiple-step synthesis may limit its widespread applications in the clinic. In this study, we developed a simple lyophilized kit for labeling PRGD2 peptide ((18)F-AlF-NOTA-PRGD2, denoted as (18)F-alfatide) using a fluoride-aluminum complex that significantly simplified the labeling procedure.
Methods: Nine patients with a primary diagnosis of lung cancer were examined by both static and dynamic PET imaging with (18)F-alfatide, and 1 tuberculosis patient was investigated using both (18)F-alfatide and (18)F-FDG imaging. Standardized uptake values were measured in tumors and other main organs at 30 min and 1 h after injection. Kinetic parameters were calculated by Logan graphical analysis. Immunohistochemistry and staining intensity quantification were performed to confirm the expression of integrin α(v)β(3).
Results: Under the optimal conditions, the whole radiosynthesis including purification was accomplished within 20 min with a decay-corrected yield of 42.1% ± 2.0% and radiochemical purity of more than 95%. (18)F-alfatide PET imaging identified all tumors, with mean standardized uptake values of 2.90 ± 0.10. Tumor-to-muscle and tumor-to-blood ratios were 5.87 ± 2.02 and 2.71 ± 0.92, respectively.
Conclusion: (18)F-alfatide can be produced with excellent radiochemical yield and purity via a simple, 1-step, lyophilized kit. PET scanning with (18)F-alfatide allows specific imaging of αvβ3 expression with good contrast in lung cancer patients. This technique might be used for the assessment of angiogenesis and for planning and response evaluation of cancer therapies that would affect angiogenesis status and integrin expression levels.
Keywords: PET; RGD peptide; alfatide; aluminum fluoride; lung cancer.