title: The development of peptide-based tools for the analysis of angiogenesis.
abstract: Limitations to the application of molecularly targeted cancer therapies are the inability to accurately match patient with effective treatment and the absence of a prompt readout of posttreatment response. Noninvasive agents that rapidly report vascular endothelial growth factor (VEGF) levels using positron emission tomography (PET) have the potential to enhance anti-angiogenesis therapies. Using phage display, two distinct classes of peptides were identified that bind to VEGF with nanomolar affinity and high selectivity. Co-crystal structures of these different peptide classes demonstrate that both bind to the receptor-binding region of VEGF. (18)F-radiolabelling of these peptides facilitated the acquisition of PET images of tumor VEGF levels in a HM7 xenograph model. The images obtained from one 59-residue probe, (18)F-Z-3B, 2 hr postinjection are comparable to those obtained with anti-VEGF antibody B20 72 hr postinjection. Furthermore, VEGF levels in growing SKOV3 tumors were followed using (18)F-Z-3B as a PET probe with VEGF levels increasing with tumor size.
authors.affiliation: Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Fedorova
authors.forename: Kerry
authors.initials: K
authors.lastname: Zobel
authors.forename: Herman S
authors.initials: HS
authors.lastname: Gill
authors.forename: Annie
authors.initials: A
authors.lastname: Ogasawara
authors.forename: Judith E
authors.initials: JE
authors.lastname: Flores
authors.forename: Jeff N
authors.initials: JN
authors.lastname: Tinianow
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Vanderbilt
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Y Gloria
authors.initials: YG
authors.lastname: Meng
authors.forename: Simon-P
authors.initials: SP
authors.lastname: Williams
authors.forename: Christian
authors.initials: C
authors.lastname: Wiesmann
authors.forename: Jeremy
authors.initials: J
authors.lastname: Murray
authors.forename: Jan
authors.initials: J
authors.lastname: Marik
authors.forename: Kurt
authors.initials: K
authors.lastname: Deshayes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057930:Click Chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D055503:Protein Multimerization; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019151:Peptide Library; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A