Pilot prospective evaluation of 18F-FPPRGD2 PET/CT in patients with cervical and ovarian cancer

Purpose We report the effect of antiangiogenic therapy on the biodistribution of F-18-FPPRGD(2) (a surrogate biomarker of integrin alpha(v)beta(3) expression), and the potential of F-18-FPPRGD(2) to predict the prognosis in patients with cervical cancer and ovarian cancer in this clinical scenario. Methods Data from six women, age range 30 - 59 years (mean +/- SD 44.0 +/- 12.5 years), who had undergone a F-18-FPPRGD(2) PET/CT scan and bevacizumab-containing therapy were prospectively collected and analyzed. We compared baseline F-18-FPPRGD(2) and F-18-FDG uptake in the lesions and tumor-to-background (T/B) ratios. The maximum and mean F-18-FPPRGD(2) standardized uptake values (SUVmax and SUVmean) were recorded for 13 normal organs, as well as in all the identified malignant lesions on the pretreatment scan and the 1-week post-treatment scan. We also measured changes in F-18-FPPRGD(2) uptake from before to 1 week after treatment(,) and compared them to the changes in F-18-FDG uptake from before to 6 weeks after treatment. Treatment outcomes were correlated with these changes. Results The uptake in lesions and T/B ratio of F-18-FPPRGD(2) were lower than those of F-18-FDG (SUVmax 3.7 +/- 1.3 vs. 6.0 +/- 1.8, P < 0.001; SUVmean 2.6 +/- 0.7 vs. 4.2 +/- 1.3, P < 0.001; T/B ratio based on SUVmax 2.4 +/- 1.0 vs. 2.6 +/- 1.0, P < 0.04; T/B ratio based on SUVmean 1.9 +/- 0.6 vs. 2.4 +/- 1.0, P < 0.003). One patient did not return for the follow-up scan and in another patient no lesions were identified on the pretreatment scan. F-18-FPPRGD(2) uptake in lesions in the remaining four patients had significantly changed 1 week after treatment (SUVmean 3.3 +/- 1.0 vs. 2.7 +/- 1.0, P < 0.001), while uptake in all normal tissues analyzed was not affected by treatment. One patient with clinical disease progression had a decrease in lesional F-18-FPPRGD(2) SUVmean of 1.6 % and in F-18-FDG SUVmean of 9.4 %. Two patients with a clinical complete response to treatment had decreases in lesional F-18-FPPRGD(2) SUVmean of 25.2 % and 25.0 % and in F-18-FDG SUVmean of 6.1 % and 71.8 %. One patient with a clinical partial response had a decrease in lesional F-18-FPPRGD(2) SUVmean of 7.9 % and in F-18-FDG SUVmean of 76.4 %. Conclusion This pilot study showed that F-18-FPPRGD(2) and F-18-FDG provide independent information about the biology of ovarian and cervical cancers. Bevacizumab-containing therapy does not affect F-18-FPPRGD(2) uptake in normal organs, but does result in statistically significant changes in lesions. In addition, F-18-FPPRGD(2) may have potential for early prediction of response to such treatments. These preliminary findings have to be confirmed in larger studies.