title: Imaging tumor endothelial marker 8 using an 18F-labeled peptide.
abstract: OBJECTIVE
  Tumor endothelial marker 8 (TEM8) has been reported to be upregulated in both tumor cells and tumor-associated endothelial cells in several cancer types. TEM8 antagonists and TEM8-targeted delivery of toxins have been developed as effective cancer therapeutics. The ability to image TEM8 expression would be of use in evaluating TEM8-targeted cancer therapy.
  
  
  METHODS
  A 13-meric peptide, KYNDRLPLYISNP (QQM), identified from the small loop in domain IV of protective antigen of anthrax toxin was evaluated for TEM8 binding and labeled with 18F for small-animal PET imaging in both UM-SCC1 head-and-neck cancer and MDA-MB-435 melanoma models.
  
  
  RESULTS
  A modified ELISA showed that QQM peptide bound specifically to the extracellular vWA domain of TEM8 with an IC50 value of 304 nM. Coupling 4-nitrophenyl 2-(18)F-fluoropropionate with QQM gave almost quantitative yield and a high specific activity (79.2±7.4 TBq/mmol, n=5) of 18F-FP-QQM at the end of synthesis. 18F-FP-QQM showed predominantly renal clearance and had significantly higher accumulation in TEM8 high-expressing UM-SCC1 tumors (2.96±0.84 %ID/g at 1 h after injection) than TEM8 low-expressing MDA-MB-435 tumors (1.38±0.56 %ID/g at 1 h after injection).
  
  
  CONCLUSIONS
  QQM peptide bound specifically to the extracellular domain of TEM8. 18F-FP-QQM peptide tracer would be a promising lead compound for measuring TEM8 expression. Further efforts to improve the affinity and specificity of the tracer and to increase its metabolic stability are warranted.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, 9 Memorial Drive, 9/1 W111, Bethesda, MD 20892, USA.
authors.forename: Qimeng
authors.initials: Q
authors.lastname: Quan
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Haokao
authors.initials: H
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
authors.forename: Henry S
authors.initials: HS
authors.lastname: Eden
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry; D001427:Bacterial Toxins / Q000737:chemistry; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D015195:Drug Design; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008545:Melanoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008840:Microfilament Proteins; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: C473287:ANTXR1 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D005462:Fluorine Radioisotopes; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C030325:anthrax toxin