Stratification of ¹⁸F-Labeled PET Imaging Agents for the Assessment of Antiangiogenic Therapy Responses in Tumors

Abstract

Successful antiangiogenic therapies have been developed for the treatment of various cancers, but not all patients respond. Therefore, the early determination of therapy efficacy is essential for patient management. This study was done to evaluate the utility of various PET imaging biomarkers for early determination of the response to therapy with the antiangiogenic agent axitinib, a multiple receptor tyrosine kinase inhibitor, in tumors with diverse biologic characteristics. Methods: Mice bearing U87-MG and MDA-MB-231 subcutaneous tumors were treated with axitinib (25 mg/kg intraperitoneally daily for 10 d), and tumor volumes were assessed with caliper measurements. The animals were concurrently imaged longitudinally with ¹⁸F-FDG, 3′-deoxy-3′-¹⁸F-fluorothymidine (¹⁸F-FLT), and 2-¹⁸F-fluoroethyl-triazolyl conjugated c(RGDyK) peptide (¹⁸F-FtRGD) to determine the optimal radiopharmaceutical for measuring the early treatment response in the 2 tumor types. Results: Daily administration of axitinib successfully retarded the growth of both U87-MG and MDA-MB-231 subcutaneous tumors, with significant differences in tumor volumes being observed from day 7 after therapy on. ¹⁸F-FDG revealed a treatment efficacy response only at day 10 after treatment in both U87-MG tumor–bearing and MDA-MB-231 tumor–bearing animals. ¹⁸F-FLT afforded earlier detection of the therapy response, revealing a significant difference between drug- and vehicle-treated animals at day 3 for animals bearing U87-MG tumors and at day 7 for animals bearing the more slowly growing MDA-MB-231 tumors. ¹⁸F-FtRGD showed a rapid change in tumor retention that reached significance by day 7 in U87-MG tumor–bearing animals; in contrast, no significant difference in tumor retention was observed in MDA-MB-231 tumor–bearing animals. Conclusion: Longitudinal imaging with different radiopharmaceuticals displays various characteristics in different tumor types, depending on their biologic characteristics. Such studies may provide clinically important information to guide patient management and monitor the response to antiangiogenic therapy with the optimum noninvasive imaging agent in the relevant cancer type.