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PET/CT imaging of renal cell carcinoma with 18F-VM4-037: a phase II pilot study

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Abstract

Background

Carbonic anhydrase IX (CA-IX) is a potential imaging biomarker of clear cell renal cell carcinoma (ccRCC). Here, we report the results of a phase II clinical trial of a small molecule radiotracer targeting CA-IX (18F-VM4-037) in ccRCC.

Methods

Between October 2012 and May 2013, 11 patients with kidney masses underwent 18F-VM4-037 PET/CT prior to surgery. Dynamic imaging was performed for the first 45 min post injection and whole-body imaging was obtained at 60 min post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.

Results

All patients tolerated the radiotracer well with no adverse events. Ten of the 11 patients had histologically confirmed malignancy. One patient had a Bosniak Type 3 cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors only in the kidney. Primary ccRCC lesions were difficult to visualize on PET alone due to high uptake of the tracer in the adjacent normal kidney parenchyma, however when viewed in conjunction with CT, the tumors were easily localized. Metastatic lesions were clearly visible on PET. Mean SUV for primary kidney lesions was 2.55 in all patients; in patients with histologically confirmed ccRCC, the mean SUV was 3.16. The time-activity curves (TAC) are consistent with reversible ligand binding with peak activity concentration at 8 min post injection followed by washout. Distribution Volume Ratio (DVR) of the lesions was measured using the Logan graphical analysis method. The mean DVR value across the 9 kidney lesions was 5.2 ± 2.8, (range 0.68–10.34).

Conclusion

18F-VM4-037 is a well-tolerated PET agent that allows same day imaging of CA-IX expression. The agent demonstrated moderate signal uptake in primary tumors and excellent visualization of CA-IX positive metastases. While the evaluation of primary ccRCC lesions is challenging due to high background activity in the normal kidney parenchyma, 18F-VM4-037 may be most useful in the evaluation of metastatic ccRCC lesions.

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Acknowledgments

This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Special thanks to the Urologic Oncology Fellows of the Urologic Oncology Branch of the National Cancer Institute, NIH; Avi Rosenberg, MD, PhD, Laboratory of Pathology, National Cancer Institute, NIH; Hartmut Kolb from Siemens and PET/NET for supplying the agent.

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    Authors and Affiliations

    1. Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA

      Baris Turkbey, Maria L. Lindenberg, Karen A. Kurdziel, Yolanda L. McKinney, Frank I. Lin & Peter L. Choyke

    2. Frederick National Laboratory for Cancer Research, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA

      Stephen Adler, Juanita Weaver, Miriam Anver, Philip Eclarinal & Gideon Kwarteng

    3. Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892-1210, USA

      Cathy D. Vocke, Nana Yaqub-Ogun, W. Marston Linehan & Adam R. Metwalli

    4. Department of Urology, SUNY Upstate, Syracuse, NY, USA

      Gennady Bratslavsky

    5. Cancer Imaging Program, National Cancer Institute, Bethesda, MD, USA

      Frank I. Lin

    6. Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA

      Maria J. Merino

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    1. Baris Turkbey
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    Correspondence to Baris Turkbey.

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    All authors declare that they have no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    Informed consent was obtained from all individual participants included in the study.

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    Baris Turkbey and Adam R. Metwalli have contributed equally to the writing and preparation of this manuscript.

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    Turkbey, B., Lindenberg, M.L., Adler, S. et al. PET/CT imaging of renal cell carcinoma with 18F-VM4-037: a phase II pilot study. Abdom Radiol 41, 109–118 (2016). https://doi.org/10.1007/s00261-015-0599-1

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