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Purpose: [F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. αβ and αβ are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [F]fluciclatide (formerly known as [F]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]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 SUV, and Patlak influx rate constant ( K) data, tumor by tumor. Results: Tumors from all 18 patients demonstrated measurable [F]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV of 6.4 ± 2.0 (range 3.8 - 10.0), while the average SUV 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]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs, with SUV 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 and αβ OD when segregating the patient population between melanoma and RCC ( r = 0.83 for K vs. melanoma and r = 0.91 for K vs. RCC). SUV showed a moderate correlation with αβ and αβ OD. Conclusion: [F]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging αβ and αβ expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression. [ABSTRACT FROM AUTHOR]