[18F]Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins

Purpose [F-18]Fluciclatide is an integrin-targeted PET radiopharmaceutical. alpha(v)beta(3) and alpha(v)beta(5) are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [F-18]fluciclatide (formerly known as [F-18]AH111585) for PET imaging of angiogenesis in melanoma and renal tumors and compare with tumor integrin expression. Methods Eighteen evaluable patients with solid tumors >= 2.0 cm underwent [F-18]fluciclatide PET/CT. All patients underwent surgery and tumor tissue samples were obtained. Immunohistochemical (IHC) staining with mouse monoclonal antibodies and diaminobenzidine (DAB) was applied to snap-frozen tumor specimens, and additional IHC was done on formalin-fixed paraffin-embedded samples. DAB optical density (OD) data from digitized whole-tissue sections were compared with PET SUV80% max, and Patlak influx rate constant (K (i)) data, tumor by tumor. Results Tumors from all 18 patients demonstrated measurable [F-18]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV80% max of 6.4 +/- 2.0 (range 3.8 - 10.0), while the average SUV80% max for metastatic melanoma lesions (in 6 patients) was 3.0 +/- 2.0 (range 0.7 - 6.5). There was a statistically significant difference in [F-18]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs, with SUV80% max of 8.2 +/- 1.8 and 5.4 +/- 1.4 (P = 0.020) and tumor-to-normal kidney (T/N) ratios of 1.5 +/- 0.4 and 0.9 +/- 0.2, respectively (P = 0.029). The highest Pearson's correlation coefficients were obtained when comparing Patlak K-i and alpha(v)beta(5) OD when segregating the patient population between melanoma and RCC (r = 0.83 for K-i vs. melanoma and r = 0.91 for K-i vs. RCC). SUV80% max showed a moderate correlation with alpha(v)beta(5) and alpha(v)beta(3) OD. Conclusion [F-18]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging alpha(v)beta(3) and alpha(v)beta(5) expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [F-18]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.