title: 89Zr-Bevacizumab PET: Potential Early Indicator of Everolimus Efficacy in Patients with Metastatic Renal Cell Carcinoma.
abstract: Currently, biomarkers that predict the efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans on mRCC patients with89Zr-bevacizumab, a VEGF-A-binding antibody tracer. The aims were to determine a change in tumor tracer uptake after the start of everolimus and to explore whether89Zr-bevacizumab PET can identify patients with early disease progression.Methods:89Zr-bevacizumab PET was done before and 2 and 6 wk after the start of everolimus, 10 mg/d, in mRCC patients. Routine CT scans were performed at baseline and every 3 mo thereafter. Tumor tracer uptake was quantified using SUVmaxThe endpoints were a change in tumor tracer uptake and treatment response on CT after 3 mo.Results:Thirteen patients participated. The median SUVmaxof 94 tumor lesions was 7.3 (range, 1.6-59.5). Between patients, median tumor SUVmaxvaried up to 8-fold. After 2 wk, median SUVmaxwas 6.3 (1.7-62.3), corresponding to a mean decrease of 9.1% (P< 0.0001). Three patients discontinued everolimus early. At 6 wk, a mean decrease in SUVmaxof 23.4% compared with baseline was found in 70 evaluable lesions of 10 patients, with a median SUVmaxof 5.4 (1.1-49.4,P< 0.0001). All 10 patients who continued treatment had stable disease at 3 mo.Conclusion:Everolimus decreases89Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate the predictive value of89Zr-bevacizumab PET for everolimus antitumor efficacy.
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: van Es
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Brouwers
authors.affiliation: Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Shekar V K
authors.initials: SVK
authors.lastname: Mahesh
authors.affiliation: Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Annemarie M
authors.initials: AM
authors.lastname: Leliveld-Kors
authors.affiliation: Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Igle J
authors.initials: IJ
authors.lastname: de Jong
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Marjolijn N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Elizabeth G E
authors.initials: EGE
authors.lastname: de Vries
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands s.oosting@umcg.nl.
authors.forename: Sjoukje F
authors.initials: SF
authors.lastname: Oosting
mesh_terms: D000368:Aged; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D016903:Drug Monitoring / Q000379:methods; D055088:Early Detection of Cancer / Q000379:methods; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D015040:Zirconium
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D000068258:Bevacizumab; D000068338:Everolimus; D015040:Zirconium
keywords: biomarker; everolimus; molecular imaging; positron emission tomography; renal cell carcinoma