Integrin αVβ3-targeted SPECT/CT for the assessment of Bevacizumab therapy in orthotopic lung cancer xenografts.

Abstract

The present study aimed to determine the utility of 99mTc-3PRGD2 single photon emission computed tomography (SPECT)/computed tomography (CT) for the non-invasive monitoring of the response of integrin αvβ3 expression to anti-angiogenic treatment with bevacizumab. Bevacizumab or vehicle therapy was performed in athymic nu/nu mice bearing A549 lung tumors (moderately high integrin αvβ3 expression) or PC-3 prostate tumors (low integrin αvβ3 expression) at a dose of 1 mg twice a week. The average tumor volume was 180±90 mm3 the day prior to baseline SPECT/CT. Longitudinal 99mTc-3PRGD2 SPECT/CT imaging was performed at baseline (−1 day) and at days 5 and 15. Tumors were harvested at all imaging time points for histopathological analysis with hematoxylin and eosin (H&E) and immunohistochemistry staining. Results revealed a significant difference in tumor volume between vehicle- and bevacizumab-treated groups at 5 and 15 days following the start of treatment in the A549 lung model (P<0.05). At 5 days after the start of therapy, the percent injected dose per gram of tissue (%ID/g) and tumor-to-muscle ratio for bevacizumab-treated A549 declined persistently (P<0.05). However, for the vehicle-treated A549 model, the %ID and %ID/g value increased 5 days after the start of treatment (P<0.05). For the PC-3 model, slow-growing tumors and low tumor uptake was observed throughout the study. Alterations in tumor vasculature were confirmed by histopathological H&E analysis and immunohistochemistry. In conclusion, longitudinal imaging using 99mTc-3PRGD2 SPECT/CT may be a useful tool for monitoring the anti-angiogenic effect of bevacizumab therapy.