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

We report the effect of antiangiogenic therapy on the biodistribution of ¹⁸F-FPPRGD₂ (a surrogate biomarker of integrin α_vβ₃ expression), and the potential of ¹⁸F-FPPRGD₂ to predict the prognosis in patients with cervical cancer and ovarian cancer in this clinical scenario.

Data from six women, age range 30 – 59 years (mean ± SD 44.0 ± 12.5 years), who had undergone a ¹⁸F-FPPRGD₂ PET/CT scan and bevacizumab-containing therapy were prospectively collected and analyzed. We compared baseline ¹⁸F-FPPRGD₂ and ¹⁸F-FDG uptake in the lesions and tumor-to-background (T/B) ratios. The maximum and mean ¹⁸F-FPPRGD₂ standardized uptake values (SUV_max and SUV_mean) 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 ¹⁸F-FPPRGD₂ uptake from before to 1 week after treatment_, and compared them to the changes in ¹⁸F-FDG uptake from before to 6 weeks after treatment. Treatment outcomes were correlated with these changes.

The uptake in lesions and T/B ratio of ¹⁸F-FPPRGD₂ were lower than those of ¹⁸F-FDG (SUV_max 3.7 ± 1.3 vs. 6.0 ± 1.8, P < 0.001; SUV_mean 2.6 ± 0.7 vs. 4.2 ± 1.3, P < 0.001; T/B ratio based on SUV_max 2.4 ± 1.0 vs. 2.6 ± 1.0, P < 0.04; T/B ratio based on SUV_mean 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. ¹⁸F-FPPRGD₂ uptake in lesions in the remaining four patients had significantly changed 1 week after treatment (SUV_mean 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 ¹⁸F-FPPRGD₂ SUV_mean of 1.6 % and in ¹⁸F-FDG SUV_mean of 9.4 %. Two patients with a clinical complete response to treatment had decreases in lesional ¹⁸F-FPPRGD₂ SUV_mean of 25.2 % and 25.0 % and in ¹⁸F-FDG SUV_mean of 6.1 % and 71.8 %. One patient with a clinical partial response had a decrease in lesional ¹⁸F-FPPRGD₂ SUV_mean of 7.9 % and in ¹⁸F-FDG SUV_mean of 76.4 %.

This pilot study showed that ¹⁸F-FPPRGD₂ and ¹⁸F-FDG provide independent information about the biology of ovarian and cervical cancers. Bevacizumab-containing therapy does not affect ¹⁸F-FPPRGD₂ uptake in normal organs, but does result in statistically significant changes in lesions. In addition, ¹⁸F-FPPRGD₂ may have potential for early prediction of response to such treatments. These preliminary findings have to be confirmed in larger studies.