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

Chen,Bin; Zhang,Wenqi; Ji,Bin; Ma,Qingjie; Li,Dandan; Gao, Shi

doi:10.3892/ol.2018.7901

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

Authors:
- Bin Chen
- Wenqi Zhang
- Bin Ji
- Qingjie Ma
- Dandan Li
- Shi Gao
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Affiliations: Department of Nuclear Medicine, China‑Japan Union Hospital of Jilin University, Erdao, Changchun 130033, P.R. China
Published online on: January 29, 2018 https://doi.org/10.3892/ol.2018.7901
Pages: 4201-4206
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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