[¹⁸F]fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ 3 and α vβ 5 integrins

Eur J Nucl Med Mol Imaging. 2014 Oct;41(10):1879-88. doi: 10.1007/s00259-014-2791-x. Epub 2014 Jun 28.


Purpose: [(18)F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. αvβ3 and αvβ5 are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [(18)F]fluciclatide (formerly known as [(18)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 [(18)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 SUV80% max, and Patlak influx rate constant (K i) data, tumor by tumor.

Results: Tumors from all 18 patients demonstrated measurable [(18)F]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 [(18)F]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 αvβ5 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 αvβ5 and αvβ3 OD.

Conclusion: [(18)F]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging αvβ3 and αvβ5 expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [(18)F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Humans
  • Integrin alphaVbeta3 / genetics
  • Integrin alphaVbeta3 / metabolism*
  • Kidney Neoplasms / diagnostic imaging*
  • Kidney Neoplasms / metabolism
  • Male
  • Melanoma / diagnostic imaging*
  • Melanoma / metabolism
  • Middle Aged
  • Multimodal Imaging
  • Peptides* / pharmacokinetics
  • Polyethylene Glycols* / pharmacokinetics
  • Positron-Emission Tomography
  • Radiopharmaceuticals* / adverse effects
  • Receptors, Vitronectin / genetics
  • Receptors, Vitronectin / metabolism*
  • Tomography, X-Ray Computed


  • AH 111585
  • Integrin alphaVbeta3
  • Peptides
  • Radiopharmaceuticals
  • Receptors, Vitronectin
  • integrin alphaVbeta5
  • Polyethylene Glycols