Pilot prospective evaluation of 18F-FPPRGD2 PET/CT in patients with cervical and ovarian cancer
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We report the effect of antiangiogenic therapy on the biodistribution of 18F-FPPRGD2 (a surrogate biomarker of integrin αvβ3 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 (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 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 (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. 18F-FPPRGD2 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 18F-FPPRGD2 SUVmean of 1.6 % and in 18F-FDG SUVmean of 9.4 %. Two patients with a clinical complete response to treatment had decreases in lesional 18F-FPPRGD2 SUVmean of 25.2 % and 25.0 % and in 18F-FDG SUVmean of 6.1 % and 71.8 %. One patient with a clinical partial response had a decrease in lesional 18F-FPPRGD2 SUVmean of 7.9 % and in 18F-FDG SUVmean 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.
Keywords18F-FPPRGD2 PET/CT Cervical cancer Ovarian cancer Bevacizumab
We thank our research coordinators, the radiochemistry staff, and the nuclear medicine technologists. We particularly thank all the patients who agreed to participate in the study and their families.
Compliance with ethical standards
The Mary Lake Polan Endowment supported the research activities of O.D. and this project.
Conflict of interest
S.S.G. Activities related to the present article: none to disclose. Activities not related to the present article: on the board of Endra, Enlight, ImaginAB, MagArray, SiteOne Therapeutics, VisualSonics/Sonosite, and Click Diagnostics; consultant for VisualSonics/Sonosite, Gamma Medica, BMEB, and Bracco; received grants from General Electric and Sanofi-Aventis; received honoraria from Imaging AB; holds stock in Enlight and VisualSonics/Sonosite; received compensation for travel and accommodations from Gamma Camera.
A.I. Activities related to the present article: none to disclose. Activities not related to the present article: received grants from GE Healthcare and Bayer Healthcare.
The other authors declare no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Department discretionary funds (O.D.).
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