Evaluation of (99m)Tc‐3PRGD(2) SPECT imaging on angiogenesis in animal models of lung cancer

BACKGROUND: The main purpose of the study was to evaluate the activity and selectivity of (99m)Tc‐3PRGD(2) SPECT/CT and (18)F‐FDG PET‐CT in order to detect the neovascularization of A549 cell subcutaneously transplanted tumors, and clarify the relationship among tumor vasculature, hypoxia and cell proliferation in the tumor microenvironment. METHODS: We established a subcutaneous tumor model, and used (99m)Tc‐3PRGD(2) SPECT/CT and (18)F‐FDG PET‐CT when the average tumor size reached 0.3–0.5 cm(3). The mice were anesthetized and sacrificed and the tumors were completely removed for frozen section analysis. We subsequently evaluated the status of neovascularization, hypoxia, as well as cell proliferation via immunofluorescence staining (IF) by detecting CD31, pimonidazole and EdU, respectively. RESULTS: There was a significant positive correlation (r = 0.88, p < 0.05) between the microvascular density (41.20 ± 18.60) and tumor to nontumor ratio (T/M), which was based on the value of (99m)Tc‐3PRGD(2) (4.20 ± 1.33); meanwhile, no significance (r = −0.16, p > 0.05) was found between the T/M and hypoxic area (116.71 ± 9.36). Neovascular proliferation was particularly vigorous in the parenchymal region of the tumor, while the cells around the cavity were generally hypoxic. (99m)TC‐3PRGD(2) SPECT/CT was more specific than (18)F‐FDG PET‐CT in detecting malignant tumors. CONCLUSION: Both (99m)TC‐3PRGD(2) and (18)F‐FDG PET‐CT can be used for the detection of malignant tumors, but the specificity and accuracy of (99m)TC‐3PRGD(2) are better. The subcutaneous tumors showed a heterogeneous microenvironment as a result of neovascularization, a high proliferation rate of cancer cells as well as subsequent hypoxia, while most of the hypoxic areas appeared around the cavities of the vessels.