18F FPPRGD2 in breast cancer subjects: A novel PET radiopharmaceutical for imaging αvβ3 integrin levels

Objectives Angiogenesis is essential for tumor growth. The expression of αvβ3 on vascular endothelium has a key role in this process. We have developed a novel PET radiopharmaceutical, 18F FPPRGD2 that is based on a dimeric RGD peptide and targets the expression of αvβ3 integrins. We present data on the first breast cancer subjects imaged with this tracer.

Methods Six female subjects with breast cancer (average age: 54.7±9.8) were recruited. 18F FPPRGD2 and 18F FDG PET/CT were subsequently performed within 2 weeks for each subject. The lesions detected with each test were tabulated. Vital signs and EKGs were obtained at regular intervals. Blood samples were obtained before the injection of 18F FPPRGD2, as well as at 24 hours and 1 week post-injection.

Results 18F FPPRGD2 was tolerated without significant alterations in vitals, EKGs, or lab values. There was stable distribution in all patients with primary clearance through the kidneys, as well as the liver, spleen, and bowel. When the primary breast lesion was present (n=3), there was intense uptake of 18F FPPRGD2 at 45 minutes post-injection, with SUVmax values ranging 8.1-9.4 (average: 8.75±0.9), compared to 18F FDG uptake with SUVmax value of 11.9. Metastatic lesions (n=11) also showed intense uptake of 18F FPPRGD2, with SUVmax values ranging 4.8-9.4 (average: 7.12±1.9), compared to 18F FDG uptake with SUVmax values ranging 2.2-4.8 (average: 3.13±1.4).

Conclusions 18F FPPRGD2 is a safe PET radiopharmaceutical, with desirable pharmacokinetic and biodistribution characteristics for imaging αvβ3-integrin expression. Testing of 18F FPPRGD2 in subjects with breast cancer demonstrates high uptake in the primary and in the metastatic lesions. Additional evaluation with larger cohorts is required to confirm these preliminary findings.

Research Support Stanford Cancer Cente