title: 89Zr-bevacizumab PET visualizes heterogeneous tracer accumulation in tumor lesions of renal cell carcinoma patients and differential effects of antiangiogenic treatment.
abstract: No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before and during antiangiogenic treatment in a pilot study.
  
  
  METHODS
  Patients underwent (89)Zr-bevacizumab PET scans at baseline and 2 and 6 wk after initiating either bevacizumab (10 mg/kg every 2 wk) with interferon-α (3-9 million IU 3 times/wk) (n = 11) or sunitinib (50 mg daily, 4 of every 6 wk) (n = 11). Standardized uptake values were compared with plasma VEGF-A and time to disease progression.
  
  
  RESULTS
  (89)Zr-bevacizumab PET scans visualized 125 evaluable tumor lesions in 22 patients, with a median SUV(max) (maximum standardized uptake value) of 6.9 (range, 2.3-46.9). Bevacizumab/interferon-α induced a mean change in tumor SUV(max) of -47.0% (range, -84.7 to +20.0%; P < 0.0001) at 2 wk and an additional -9.7% (range, -44.8 to +38.9%; P = 0.015) at 6 wk. In the sunitinib group, the mean change in tumor SUV(max) was -14.3% at 2 wk (range, -80.4 to +269.9; P = 0.006), but at 6 wk the mean change in tumor SUV(max) was +72.6% (range, -46.4 to +236%; P < 0.0001) above baseline. SUV(max) was not related to plasma VEGF-A at all scan moments. A baseline mean tumor SUV(max) greater than 10.0 in the 3 most intense lesions corresponded with longer time to disease progression (89.7 vs. 23.0 wk; hazard ratio, 0.22; 95% confidence interval, 0.05-1.00).
  
  
  CONCLUSIONS
  Tumor uptake of (89)Zr-bevacizumab is high in mRCC, with remarkable interpatient and intrapatient heterogeneity. Bevacizumab/interferon-α strongly decreases tumor uptake whereas sunitinib results in a modest reduction with an overshoot after 2 drug-free weeks. High baseline tumor SUV(max) was associated with longer time to progression.
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands s.oosting@umcg.nl.
authors.forename: Sjoukje F
authors.initials: SF
authors.lastname: Oosting
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Brouwers
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: van Es
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wouter B
authors.initials: WB
authors.lastname: Nagengast
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Thijs H
authors.initials: TH
authors.lastname: Oude Munnink
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Hospital and Clinical Pharmacy, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marjolijn N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Johan R
authors.initials: JR
authors.lastname: de Jong
authors.affiliation: Department of Urology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Igle J
authors.initials: IJ
authors.lastname: de Jong
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Sanne
authors.initials: S
authors.lastname: de Haas
authors.affiliation: Genentech, San Francisco, California; and.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Scherer
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Sluiter
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Alfons H H
authors.initials: AH
authors.lastname: Bongaerts
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000378:metabolism* / Q000627:therapeutic use; D000068258:Bevacizumab; D001692:Biological Transport; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use; D011849:Radioactive Tracers; D011868:Radioisotopes; D011877:Radionuclide Imaging; D000077210:Sunitinib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D015040:Zirconium
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D016898:Interferon-alpha; D011758:Pyrroles; D011849:Radioactive Tracers; D011868:Radioisotopes; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C580636:89Zr-bevacizumab; D015040:Zirconium; D000077210:Sunitinib
keywords: bevacizumab; molecular imaging; positron emission tomography; renal cell carcinoma; sunitinib