title: VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment.
abstract: Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments for cancer. In this study, we evaluated the role of VEGF-PET as a biomarker of dynamic angiogenic changes in tumors following treatment with the kinase inhibitor sunitinib. The effects of sunitinib treatment and withdrawal on the tumor was investigated using the new VEGF-PET tracer (89)Zr-ranibizumab as well as (18)F-FDG PET, and (15)O-water PET in mouse xenograft models of human cancer. The obtained imaging results were compared with tumor growth, VEGF plasma levels and immunohistologic analyzes. In contrast to (18)F-FDG and (15)O-water PET, VEGF-PET demonstrated dynamic changes during sunitinib treatment within the tumor with a strong decline in signal in the tumor center and only minimal reduction in tumor rim, with a pronounced rebound after sunitinib discontinuation. VEGF-PET results corresponded with tumor growth and immunohistochemical vascular- and tumor- markers. Our findings highlight the strengths of VEGF-PET imaging to allow serial analysis of angiogenic changes in different areas within a tumor.
authors.affiliation: Department of Medical Oncology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wouter B
authors.initials: WB
authors.lastname: Nagengast
authors.forename: Marjolijn N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.forename: Sjoukje F
authors.initials: SF
authors.lastname: Oosting
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
authors.forename: Frank-Jan
authors.initials: FJ
authors.lastname: Warnders
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Brouwers
authors.forename: Johan R
authors.initials: JR
authors.lastname: de Jong
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Price
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Geke A P
authors.initials: GA
authors.lastname: Hospers
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Hesselink
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18; D000077210:Sunitinib