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

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

  • Abdom Radiol (NY). 2016 Jan;41(1):109-18. doi: 10.1007/s00261-015-0599-1.
Baris Turkbey 1 Maria L Lindenberg 2 Stephen Adler 3 Karen A Kurdziel 2 Yolanda L McKinney 2 Juanita Weaver 3 Cathy D Vocke 4 Miriam Anver 3 Gennady Bratslavsky 5 Philip Eclarinal 3 Gideon Kwarteng 3 Frank I Lin 2 6 Nana Yaqub-Ogun 4 Maria J Merino 7 W Marston Linehan 4 Peter L Choyke 2 Adam R Metwalli 8
Affiliations

Affiliations

  • 1 Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA. [email protected].
  • 2 Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
  • 3 Frederick National Laboratory for Cancer Research, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA.
  • 4 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.
  • 5 Department of Urology, SUNY Upstate, Syracuse, NY, USA.
  • 6 Cancer Imaging Program, National Cancer Institute, Bethesda, MD, USA.
  • 7 Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
  • 8 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. [email protected].
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 ((18)F-VM4-037) in ccRCC.

Methods: Between October 2012 and May 2013, 11 patients with kidney masses underwent (18)F-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.

Keywords

18F-VM4-037; Carbonic anhydrase IX; Positron emission tomography (PET); Renal cell carcinoma.

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