title: [¹⁸F]fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ 3 and α vβ 5 integrins.
abstract: OBJECTIVE
  [(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.
  
  
  CONCLUSIONS
  [(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.
authors: Molecular Imaging Program, NCI, NIH, Bethesda, MD, USA.
authors: Esther
authors: E
authors: Mena
authors: Rikard
authors: R
authors: Owenius
authors: Baris
authors: B
authors: Turkbey
authors: Richard
authors: R
authors: Sherry
authors: Gennady
authors: G
authors: Bratslavsky
authors: Sven
authors: S
authors: Macholl
authors: Matthew P
authors: MP
authors: Miller
authors: Ed J
authors: EJ
authors: Somer
authors: Liza
authors: L
authors: Lindenberg
authors: Stephen
authors: S
authors: Adler
authors: Joanna
authors: J
authors: Shih
authors: Peter
authors: P
authors: Choyke
authors: Karen
authors: K
authors: Kurdziel
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D008875:Middle Aged; D064847:Multimodal Imaging; D010455:Peptides / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000009:adverse effects; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: C530281:AH 111585; D039302:Integrin alphaVbeta3; D010455:Peptides; D019275:Radiopharmaceuticals; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D011092:Polyethylene Glycols