First in human evaluation of a newly developed integrin binding PET tracer, 18F-RGD-K5 in patients with breast cancer: Comparison with 18F-FDG uptake pattern and microvessel density

Objectives The purpose of this study was to evaluate a newly developed integrin binding agent, 18F-RGD-K5 (alternative to 18F-Galacto-RGD) in breast cancer and compared with 18F-FDG PET scan. The uptake pattern of 18F-RGD-K5 was also compared with microvessel density in tumor specimen.

Methods Twelve patients with primary or metastatic breast cancer were enrolled. 18F-FDG PET scan was performed within ±7 days of 18F-RGD-K5 PET scan. The maximum SUV within the lesions were measured in each scan. Biopsy specimen was obtained in 9 patients and immunohistochemistry using MoAb against CD31 was performed. The maximum vessel density (hot-spot), the number of microvessels (MVD), and areas occupied by vessel lumens (vessel area) were calculated within 10 randomly selected areas in each tumor specimen.

Results No adverse reaction was found in all patients. Of the 12 patients, 157 lesions were identified in 10 patients on 18F-FDG PET scan. Among them, 122 lesions (77.7%) show increased 18F-RGD-K5 uptake. 18F-FDG uptake was higher in 98, and similar uptake in 19, however, 18F-RGD-K5 uptake was higher in 5. No correlation was found between SUV of 18F-RGD-K5 and 18F-FDG (r=0.170, p=0.661), hot-spot (r=0.445, p=0.230), MVD (r=0.298, p=0.437), or vessel area (r=0.012, p=0.976).

Conclusions The 18F-RGD-K5 is a useful marker for integrin expression in breast cancer, but it does not appear to be well correlated with angiogenesis with MVD since RGD peptide binds to not only αvβ3 receptor but also to many other subtypes of integrin that are expressed in breast cancer cells.