title: 89Zr-Bevacizumab PET Visualizes Disease Manifestations in Patients with von Hippel-Lindau Disease.
abstract: Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable, and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor A (VEGF-A) produced locally is supposed to play an important role in development of disease manifestations and is a target for antiangiogenic therapy with the monoclonal antibody bevacizumab. We aimed to assess whether VHL manifestations can be visualized with (89)Zr-bevacizumab PET and to explore whether (89)Zr-bevacizumab PET can differentiate progressive from nonprogressive lesions.
  
  
  
  VHL patients with at least 1 measurable hemangioblastoma were eligible. (89)Zr-bevacizumab (37 MBq) was administered intravenously 4 d before the scan. Maximum standardized uptake values were calculated. PET scans were fused with routine MRI of the central nervous system and abdominal MRI or CT. Progressive lesions were defined as new lesions, lesions that became symptomatic, and lesions ≥ 10 mm that increased ≥ 10% and ≥ 4 mm on repeated anatomic imaging within 12 mo.
  
  
  
  Twenty-two patients were enrolled. At baseline, anatomic imaging showed 311 lesions. (89)Zr-bevacizumab PET visualized 59 VHL manifestations, 0-17 per patient. The median of maximum standardized uptake values was 8.5 (range, 1.3-35.8). The detection rate for lesions ≥ 10 mm was 30.8%. Seven additional hotspots without substrate on baseline anatomic imaging were found; 2 were also detected with anatomic imaging during follow-up. Nine of 25 progressive lesions were visible on PET and 27 of 175 nonprogressive lesions, corresponding to a positive predictive value of 25% and a negative predictive value of 90%. SUVmax was similar in progressive and nonprogressive lesions (median, 4.8; range, 0.9-8.9 vs. median, 6.7; range, 1.3-35.8, P = 0.14).
  
  
  
  VHL manifestations can be visualized with (89)Zr-bevacizumab PET with a striking heterogeneity in tracer accumulation. (89)Zr-bevacizumab uptake does not predict progression within 12 mo. In one third of the lesions, the drug target VEGF is available and accessible. (89)Zr-bevacizumab PET might offer a tool to select VHL patients for anti-VEGF therapy.
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sjoukje F
authors.initials: SF
authors.lastname: Oosting
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sophie J
authors.initials: SJ
authors.lastname: van Asselt
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 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 Radiology, Martini Hospital Groningen, Groningen, The Netherlands.
authors.forename: Julia D J
authors.initials: JD
authors.lastname: Steinberg
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 Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 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 Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anouk N A
authors.initials: AN
authors.lastname: van der Horst-Schrivers
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Annemiek M E
authors.initials: AM
authors.lastname: Walenkamp
authors.affiliation: Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and.
authors.forename: Eelco W
authors.initials: EW
authors.lastname: Hoving
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Sluiter
authors.affiliation: Department of Internal Medicine, University of Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Zonnenberg
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
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands t.p.links@umcg.nl.
authors.forename: Thera P
authors.initials: TP
authors.lastname: Links
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics*; D000068258:Bevacizumab; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult; D015040:Zirconium; D006623:von Hippel-Lindau Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D000068258:Bevacizumab; C580636:89Zr-bevacizumab; D015040:Zirconium
keywords: bevacizumab; hemangioblastoma; positron emission tomography; vascular endothelial growth factor; von Hippel-Lindau disease