Glioblastoma PET/MRI: kinetic investigation of [ 18 F]rhPSMA-7.3, [ 18 F]FET and [ 18 F]fluciclovine in an orthotopic mouse model of cancer
European Journal of Nuclear Medicine and Molecular Imaging(2022)
摘要
Purpose Glioblastoma multiforme (GBM) is the most common glioma and standard therapies can only slightly prolong the survival. Neo-vascularization is a potential target to image tumor microenvironment, as it defines its brain invasion. We investigate [ 18 F]rhPSMA-7.3 with PET/MRI for quantitative imaging of neo-vascularization in GBM bearing mice and human tumor tissue and compare it to [ 18 F]FET and [ 18 F]fluciclovine using PET pharmacokinetic modeling (PKM). Methods [ 18 F]rhPSMA-7.3, [ 18 F]FET, and [ 18 F]fluciclovine were i.v. injected with 10.5 ± 3.1 MBq, 8.0 ± 2.2 MBq, 11.5 ± 1.9 MBq ( n = 28, GL261-luc2) and up to 90 min PET/MR imaged 21/28 days after surgery. Regions of interest were delineated on T2-weighted MRI for (i) tumor, (ii) brain, and (iii) the inferior vena cava. Time-activity curves were expressed as SUV mean, SUVR and PKM performed using 1-/2-tissue-compartment models (1TCM, 2TCM), Patlak and Logan analysis (LA). Immunofluorescent staining (IFS), western blotting, and autoradiography of tumor tissue were performed for result validation. Results [ 18 F]rhPSMA-7.3 showed a tumor uptake with a tumor-to-background-ratio (TBR) = 2.1–2.5, in 15–60 min. PKM (2TCM) confirmed higher K1 (0.34/0.08, p = 0.0012) and volume of distribution V T (0.24/0.1, p = 0.0017) in the tumor region compared to the brain. Linearity in LA and similar k3 = 0.6 and k4 = 0.47 (2TCM, tumor, p = ns) indicated reversible binding. K1, an indicator for vascularization, increased (0.1/0.34, 21 to 28 days, p < 0.005). IFS confirmed co-expression of PSMA and tumor vascularization. [ 18 F]fluciclovine showed higher TBR (2.5/1.8, p < 0.001, 60 min) and V S (1.3/0.7, p < 0.05, tumor) compared to [ 18 F]FET and LA indicated reversible binding. V T increased ( p < 0.001, tumor, 21 to 28 days) for [ 18 F]FET (0.5–1.4) and [ 18 F]fluciclovine (0.84–1.5). Conclusion [ 18 F]rhPSMA-7.3 showed to be a potential candidate to investigate the tumor microenvironment of GBM. Following PKM, this uptake was associated with tumor vascularization. In contrast to what is known from PSMA-PET in prostate cancer, reversible binding was found for [ 18 F]rhPSMA-7.3 in GBM, contradicting cellular trapping. Finally, [ 18 F]fluciclovine was superior to [ 18 F]FET rendering it more suitable for PET imaging of GBM.
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关键词
Glioblastoma,PET/MRI,Amino acid transport,PSMA,Neo-vascularization
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