PET imaging of tumor angiogenesis and monitoring of Endostar anti-angiogenic efficacy in Lewis lung carcinoma model using integrin αvβ3-selective radiotracer 68Ga-3PRGD2

Objectives Angiogenesis is a fundamental requirement for tumor growth and therefore it is a primary target for anti-cancer therapy. Integrin αvβ3 expression on angiogenic blood vessels (as well as on some tumor types) can be assessed and quantified noninvasively using radiolabeled RGD peptides for positron emission tomography (PET). In this study, we examined the anti-angiogenic activities of endostar (a novel recombinant human endostatin) delivered by daily systemic administration in Lewis lung carcinoma (LLC) model. PET imaging were performed during the Endostar treatment to monitor the anti-angiogenic efficacy in LLC model using integrin αvβ3-selective radiotracer 68Ga-3PRGD2.

Methods Thirty-two LLC tumor bearing mice were randomly divided into two groups. The treatment group were administrated with Endostar (8 mg/kg/day) via tail vein injection, the control group were administrated with saline. The PET imaging was performed at day 3, day 7, day 14 and day 21 post-treatment, respectively. Tumors were evaluated by immunohistochemistry and western blot analysis.

Results Three weeks of systemic administration of endostar led to ~90% (P <0.005) reduction of tumor volumes with decreased microvessel densities (P <0.05) and integrin αvβ3 expresssion (P <0.05). Monitoring the tumor response to Endostar using PET tracer 68Ga-3PRGD2 showed a reduction of tracer uptake only three days after anti-angiogenic treatment.

Conclusions The PET imaging of 68Ga-3PRGD2 tracer could identify the expression status of integrin αvβ3 after Endostar treatment. These studies support the concept of imaging angiogenesis with integrin αvβ3-targeted tracers to monitor the course of anti-angiogenic therapy and to inform about the response noninvasively over time in the clinic. The comparative PET imaging with 18F-FDG and 68Ga-3PRGD2 for monitoring Endostar therapy efficacy is in progress.