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

Abstract

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.

• Authors: Esther Mena, Rikard Owenius, Baris Turkbey, Richard Sherry, Gennady Bratslavsky, Sven Macholl, Matthew P Miller, Ed J Somer, Liza Lindenberg, Stephen Adler, Joanna Shih, Peter Choyke, Karen Kurdziel
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 41 Issue 10 Pg. 1879-88 (Oct 2014) ISSN: 1619-7089 [Electronic] Germany
• PMID: 24973039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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