Can 111In-RGD2 monitor response to therapy in head and neck tumor xenografts?

Abstract

RGD (arginylglycylaspartic acid)-based imaging tracers allow specific imaging of integrin αvβ expression, proteins overexpressed during angiogenesis; however, few studies have investigated the potential of these tracers to monitor responses of antiangiogenic or radiation therapy. In the studies presented here, 111In-RGD2 was assessed for its potential as an imaging tool to monitor such responses to therapies. Methods: DOTA-E-[c(RGDfK)]2 was radiolabeled with 111In (111In-RGD2), and biodistribution studies were performed in mice with subcutaneous FaDu or SK-RC-52 xenografts after treatment with either antiangiogenic therapy (bevacizumab or sorafenib) or tumor irradiation (10 Gy). Micro-SPECT imaging studies and subsequent quantitative analysis were also performed. The effect of bevacizumab, sorafenib, or radiation therapy on tumor growth was determined. Results: The uptake of 111In- RGD2 in tumors, as determined from biodistribution studies, correlated well with that quantified from micro-SPECT images, and both showed that 15 d after irradiation 111In-RGD2 uptake was enhanced. Specific or nonspecific uptake of 111In-RGD2 in FaDu or SK-RC-52 xenografts was not affected after antiangiogenic therapy, except in head and neck squamous cell carcinoma 19 d after the start of sorafenib therapy (P , 0.05). The uptake of 111In-RGD2 followed tumor volume in studies featuring antiangiogenic therapy. However, the uptake of 111In-RGD2 in FaDu xenografts was decreased as early as 4 h after tumor irradiation, despite nonspecific uptake remaining unaltered. Tumor growth was inhibited after antiangiogenic or radiation therapy. Conclusion: Here, it is suggested that 111In-RGD2 could allow in vivo monitoring of angiogenic responses after radiotherapy and may therefore prove a good clinical tool to monitor angiogenic responses early after the start of radiotherapy in patients with head and neck squamous cell carcinoma. Despite clear antitumor efficacy, antiangiogenic therapy did not alter tumor uptake of 111In-RGD2, indicating that integrin expression was not altered.