title: PET/CT imaging of renal cell carcinoma with (18)F-VM4-037: a phase II pilot study.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA. turkbeyi@mail.nih.gov.
authors.forename: Baris
authors.initials: B
authors.lastname: Turkbey
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Lindenberg
authors.affiliation: Frederick National Laboratory for Cancer Research, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Adler
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Kurdziel
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Yolanda L
authors.initials: YL
authors.lastname: McKinney
authors.affiliation: Frederick National Laboratory for Cancer Research, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA.
authors.forename: Juanita
authors.initials: J
authors.lastname: Weaver
authors.affiliation: 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.
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Vocke
authors.affiliation: Frederick National Laboratory for Cancer Research, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Anver
authors.affiliation: Department of Urology, SUNY Upstate, Syracuse, NY, USA.
authors.forename: Gennady
authors.initials: G
authors.lastname: Bratslavsky
authors.affiliation: Frederick National Laboratory for Cancer Research, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Eclarinal
authors.affiliation: Frederick National Laboratory for Cancer Research, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA.
authors.forename: Gideon
authors.initials: G
authors.lastname: Kwarteng
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.|Cancer Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Frank I
authors.initials: FI
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Nana
authors.initials: N
authors.lastname: Yaqub-Ogun
authors.affiliation: Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.affiliation: 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.
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: 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. adam.metwalli@nih.gov.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Metwalli
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D003287:Contrast Media; D003937:Diagnosis, Differential; D004151:Dipeptides; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D013449:Sulfonamides; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: C000598170:3-(4-(2-fluoroethoxy)phenyl)-2-(3-methyl-2-(4-((2-sulfamoylbenzo(d)thiazol-6-yloxy)methyl)-1H-1,2,3-triazol-1-yl)butanamido)propanoic acid; D014408:Biomarkers, Tumor; D003287:Contrast Media; D004151:Dipeptides; D019275:Radiopharmaceuticals; D013449:Sulfonamides; D019788:Fluorodeoxyglucose F18; D002256:Carbonic Anhydrases
keywords: 18F-VM4-037; Carbonic anhydrase IX; Positron emission tomography (PET); Renal cell carcinoma
references.citation: Clin Imaging. 2012 Nov-Dec;36(6):660-73
references.pmid: 23153993
references.citation: Science. 1993 May 28;260(5112):1317-20
references.pmid: 8493574
references.citation: J Clin Oncol. 2007 Oct 20;25(30):4757-64
references.pmid: 17947723
references.citation: Clin Cancer Res. 2003 Feb;9(2):802-11
references.pmid: 12576453
references.citation: J Clin Oncol. 2004 Dec 15;22(24):4991-5004
references.pmid: 15611513
references.citation: Urol Clin North Am. 2012 May;39(2):133-48, v
references.pmid: 22487757
references.citation: Cell Death Differ. 2008 Apr;15(4):678-85
references.pmid: 18259193
references.citation: Int J Cancer. 2008 Jul 15;123(2):395-400
references.pmid: 18464292
references.citation: J Clin Oncol. 1993 Apr;11(4):738-50
references.pmid: 8478666
references.citation: Clin Cancer Res. 1998 Nov;4(11):2729-39
references.pmid: 9829736
references.citation: Eur Urol. 2013 Sep;64(3):478-85
references.pmid: 22980441
references.citation: Mol Imaging Biol. 2014 Oct;16(5):739-46
references.pmid: 24696183
references.citation: Nat Rev Cancer. 2008 Nov;8(11):865-73
references.pmid: 18923434
references.citation: J Nucl Med. 2011 Apr;52(4):535-40
references.pmid: 21421715
references.citation: J Urol. 2003 Dec;170(6 Pt 1):2163-72
references.pmid: 14634372
references.citation: Eur Urol. 2013 Jun;63(6):1101-6
references.pmid: 23453421
references.citation: PET Clin. 2015 Jul;10(3):361-74
references.pmid: 26099672
references.citation: Lancet Oncol. 2007 Apr;8(4):304-10
references.pmid: 17395103
references.citation: Histopathology. 2011 Dec;59(6):1229-39
references.pmid: 22175902
references.citation: Cell Oncol (Dordr). 2011 Jun;34(3):225-34
references.pmid: 21547579
references.citation: J Nucl Med. 2007 Mar;48(3):471-80
references.pmid: 17332626
references.citation: Br J Cancer. 2003 Jul 7;89(1):2-7
references.pmid: 12838292