Evaluation of the anti-tumoral therapy effect of antiangiogenesis drugs using hypoxia imaging in animal models

Objectives Evaluation of anti-angiogenenic therapeutic response using hypoxic (18F-MISO) and metabolic (18F-FDG) radiotracers to evaluate hypoxia and angiogenesis response in a tumor animal model.

Methods HCT116, a human colorectal cancer cell line, was subcutaneously implanted into BALB/c-nu mice. One month later, when the tumor size was 1.0cm, pre-therapy 18F-FDG and 18F-MISO was obtained within two days. Immediately after PET images, Avastin (5mg/kg) was injection intraperitoneally, 2 times a week, for 10 days. Tumor size was recorded daily. Post-therapy PET images were obtained at the end of therapy, using the same imaging protocols as previously mentioned. Immediately after 18F-MISO PET images, the animals were sacrificed and immunohistochemical staining was performed and correlated with PET images.

Results Avastin treated group showed growth stasis compared to control group. Pre-therapy PET images showed homogenous uptake in both 18F-MISO and 18F-FDG. After Avastin therapy, 18F-FDG PET images showed a photon defect in the central portion with peripheral uptake. 18F-MISO showed mild increased uptake in the central portion with peripheral uptake. In the control group, both 18F-MISO and 18F-FDG showed a central photon defect and a thick ring of peripheral uptake. Autoradiography of both 18F-MISO and 18F-FDG was correlated with immunohistochemical staining showed treated group had ‘nests’ of viable tumors scattered throughout the tumor with hypoxic areas surrounding the intratumoral microvessels. The control group showed central necrosis with a thick rim of viable tumor cells. 18F-MISO PET images more closely reflected the viable, hypoxic tumor cells in the central portions of the tumor compared to 18F-FDG.

Conclusions 18F-FDG and 18F-MISO shows different uptake patterns in HCT116 xenograft tumors. 18F-MISO uptake was more extensive throughout the tumor compared to 18F-FDG uptake, suggesting that 18F-MISO reflects hypoxic, viable cells better than 18F-FDG, which suggests that 18F-MISO may evaluate Avastin treatment response better