F-18 FLT bests other F-18 labeled agents for antiangiogenic therapy response

Angiogenesis is a hallmark of invasive cancer and antiangiogenesis therapies are gaining momentum, but some patients do not respond well. F-18 FLT may be the strongest contender out of three F-18 labeled PET agents used to evaluate early response to therapy, which aims to improve patient management and negate unnecessary treatments, according to research published August 1 in the Journal of Nuclear Medicine.

Julian L. Goggi, PhD, from the Singapore Bioimaging Consortium, Helios, Singapore, and colleagues pored over results of preclinical PET scans using F-18 FDG, FLT and FtRGD in mice with heterogeneous glioma (U87-MG) and breast ductal carcinoma (MDA-MB-231) treated daily for 10 days with the multiple receptor tyrosine kinase inhibitor axitinib. The three imaging agents point to contrasting tumor characteristics involved in angiogenesis, with FDG looking for glucose metabolism, FLT for proliferation and FtRGD specifically for angiogenesis. Findings of the study showed F-18 FLT was able to image response to therapy sooner, with the other two revealing limitations.

“F-18 FLT afforded earlier detection of the therapy response, revealing a significant difference between drug- and vehicle-treated animals at day three for animals bearing U87-MG tumors and at day seven for animals bearing the more slowly growing MDA-MB-231 tumors,” wrote Goggi et al. “F-18 FtRGD showed a rapid change in tumor retention that reached significance by day seven in U87-MG tumor–bearing animals; in contrast, no significant difference in tumor retention was observed in MDA-MB-231 tumor–bearing animals.”

F-18 FDG was also able to assess response to therapy with axitinib in both kinds of tumors, but only at day 10 of treatment for both cancers and complications arising from inflammation and benign nonpathologic tissues can make clear assessment with FDG a challenge. F-18 FLT beat the other two in both timeframe and effectiveness across tumor types. The especially early response using FLT for glioma was attributed to the prominent vascular effects in these fast-growing tumors.

While FLT was comparatively better than the other two PET agents in this study, the objective was not to pick the best option, but to compare the strengths and weaknesses of all three for more personalized patient monitoring.

“The ability of each of these radiopharmaceuticals to measure therapy efficacy after treatment with the antiangiogenic agent axitinib appears to be dependent on the characteristics of the tumors to be evaluated,” wrote the authors. “These data suggest that differences in tumor biology may be critical for individual patient management and the choice of radiopharmaceutical agents for the noninvasive monitoring of therapy efficacy.”