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

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Abstract

Purpose

[18F]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 [18F]fluciclatide (formerly known as [18F]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 [18F]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 [18F]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 [18F]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

[18F]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. [18F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.

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Acknowledgments

We thank Adrian Smith, Derek Grant, Brian Higley and Ian Wilson from GE Healthcare, and Tanya Ledezma and Karen Yamamoto for support. We also thank Earl Henry for consultancy with the statistical analyses. This trial was sponsored by GE Healthcare.

Disclosures

The authors Rikard Owenius, Sven Macholl, Matthew P. Miller, and Ed J. Somer are affiliated with GE Healthcare. The remaining authors have no conflicts of interest.

Author information

Authors and Affiliations

  1. Molecular Imaging Program, NCI, NIH, Bethesda, MD, USA

    Esther Mena, Baris Turkbey, Liza Lindenberg, Peter Choyke & Karen Kurdziel

  2. GE Healthcare, Life Sciences, Uppsala, Sweden

    Rikard Owenius

  3. Surgery Branch, NCI, NIH, Bethesda, MD, USA

    Richard Sherry

  4. Urologic Oncology Branch, NCI, NIH, Bethesda, MD, USA

    Gennady Bratslavsky

  5. GE Healthcare, Life Sciences, Amersham, UK

    Sven Macholl, Matthew P. Miller & Ed J. Somer

  6. Clinical Research Directorate/CMRP SAIC-Frederick Inc., NCI-Frederick, Bethesda, MD, 21702, USA

    Stephen Adler

  7. Biometric Research Branch, DCTD, NCI, NIH, Rockville, MD, USA

    Joanna Shih

  8. Molecular Imaging Program, National Cancer Institute, 10 Center Dr, MSC 1182, Bldg 10, Room B3B69, Bethesda, MD, 20892-1088, USA

    Liza Lindenberg

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  1. Esther Mena
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Correspondence to Liza Lindenberg.

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Mena, E., Owenius, R., Turkbey, B. et al. [18F]Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins. Eur J Nucl Med Mol Imaging 41, 1879–1888 (2014). https://doi.org/10.1007/s00259-014-2791-x

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  • DOI: https://doi.org/10.1007/s00259-014-2791-x

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