18F-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 (18F-AlF-NOTA-PRGD2, denoted as 18F-alfatide) using a fluo-ride–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 18F-alfatide, and 1 tuberculosis patient was investigated using both 18F-alfatide and 18F-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. Immunohisto-chemistry and staining intensity quantification were performed to confirm the expression of integrin αvβ3. Results Under the optimal conditions, the whole radiosynthesis including purifica-tion was accomplished within 20 min with a decay-corrected yield of 42.1% ± 2.0% and radiochemical purity of more than 95%. 18F-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 18F-alfatide can be produced with excellent radiochemical yield and purity via a simple, 1-step, lyophilized kit. PET scanning with 18F-alfatide allows specific imaging of αvβ3 expression with good contrast in lung cancer patients. This technique might be used for the assessment of angiogene-sis and for planning and response evaluation of cancer therapies that would affect angiogenesis status and integrin expression levels.
Purpose We report the biodistribution and radiation dosimetry of an integrin αvβ3 specific PET tracer 18F-AlF-NOTA-E[PEG4-c(RGDfk)]2) (denoted as 18F-Alfatide II). We also assessed the value of 18F-Alfatide II in patients with brain metastases. Methods Series of torso (from the skull to the thigh) static images were acquired in 5 healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45 and 60 min after injection of 18F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with 18F-FDG (5.55 MBq/kg) and 18F-Alfatide II. Results Injection of 18F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. 18F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by 18F-Alfatide II PET, while only 10 were visualized by 18F-FDG, and 13 by CT. Conclusion 18F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that 18F-Alfatide II is feasible for human studies. 18F-Alfatide II has potential value in finding brain metastases of different cancer as a biomarker of angiogenesis.
This pilot prospective evaluation study is to verify the efficiency of 18F-Alfatide II, a specific PET imaging agent for integrin αvβ3, in detecting bone metastasis in human, with comparison to 18F-FDG PET. Thirty recruited patients underwent 18F-FDG and 18F-alfatide II PET/CT successively within days. The final diagnosis of bone lesions was established based on the comprehensive assessment of all available data and clinical follow-up, which fall into four groups: osteolytic, osteoblastic, mixed and bone marrow. Visual analysis and quantification of SUVmax were performed to compare the detection sensitivity of 18F-Alfatide II and 18F-FDG PET. Eleven patients were found to have a total of 126 bone metastasis lesions. 18F-Alfatide II PET can detect the bone metastatic lesions with good contrast and higher sensitivity (positive rate of 92%) than 18F-FDG PET (77%). Especially, 18F-Alfatide II PET showed superiority to 18F-FDG PET in detecting osteoblastic (70% vs. 53%) and bone marrow metastatic lesions (98% vs. 77%). In conclusion, 18F-Alfatide II PET/CT can be used to detect skeletal and bone marrow metastases, with nearly 100% sensitivity in osteolytic, mixed and bone marrow lesions. The sensitivity of 18F-Alfatide II PET/CT in osteoblastic metastases is relatively low but still significantly higher than that of 18F-FDG PET/CT. This pilot clinical study warrants the further application of 18F-Alfatide II PET/CT in metastatic lesion detection, patient management and drug therapy response monitoring.
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