Abstract
PURPOSE: To investigate and compare the dynamic positron emission tomography (PET) imaging with [(18)F]Alfatide II Imaging and [(11)C]Methionine ([(11)C]MET) in orthotopic rat models of glioblastoma multiforme (GBM), and to assess the utility of [(18)F]Alfatide II in detecting and evaluating neoangiogenesis in GBM. METHODS: [(18)F]Alfatide II and [(11)C]MET were injected into the orthotopic GBM rat models (n = 20, C6 glioma cells), followed by dynamic PET/MR scans 21 days after surgery of tumor implantation. On the PET image with both radiotracers, the MRI-based volume-of-interest (VOI) was manually delineated encompassing glioblastoma. Time-activity curves were expressed as tumor-to-normal brain ratio (TNR) parameters and PET pharmacokinetic modeling (PKM) performed using 2-tissue-compartment models (2TCM). Immunofluorescent staining (IFS), western blotting and blocking experiment of tumor tissue were performed for the validation. RESULTS: Compared to (11)C-MET, [(18)F]Alfatide II presented a persistent accumulation in the tumor, albeit with a slightly lower SUVmean of 0.79 ± 0.25, and a reduced uptake in the contralateral normal brain tissue, respectively. This resulted in a markedly higher tumor-to-normal brain ratio (TNR) of 18.22 ± 1.91. The time-activity curve (TACs) showed a significant increase in radioactive uptake in tumor tissue, followed by a plateau phase up to 60 min for [(18)F]Alfatide II (time to peak:255 s) and 40 min for [(11)C]MET (time to peak:135 s) post injection. PKM confirmed significantly higher K(1) (0.23/0.07) and K(3) (0.26/0.09) in the tumor region compared to the normal brain with [(18)F]Alfatide II. Compared to [(11)C]MET imaging, PKM confirmed both significantly higher K(1)/K(2) (1.24 ± 0.79/1.05 ± 0.39) and K(3)/K(4) (11.93 ± 4.28/3.89 ± 1.29) in the tumor region with [(18)F]Alfatide II. IFS confirmed significant expression of integrin and tumor vascularization in tumor region. CONCLUSION: [(18)F]Alfatide II demonstrates potential in imaging tumor-associated neovascularization in the context of glioblastoma multiforme (GBM), suggesting its utility as a tool for further exploration in neovascular characterization.