title: Use of Labelled tLyP-1 as a Novel Ligand Targeting the NRP Receptor to Image Glioma.
abstract: BACKGROUND
  Neuropilin (NRP) receptors are overexpressed in glioma tumor tissue, and therefore may be a potential target for imaging markers. We investigated whether labelled tLyP-1, an NRP targeting peptide, could be used as the targeting ligand for developing reagents for imaging glioma tumors.
  
  
  METHODS
  The tLyP-1 peptide (CGNKRTR) was labeled with 5-carboxyfluorescein (FAM) or 18F-fluoride. A control peptide (MAQKTSH) was also labeled with FAM. The in vitro binding between FAM-tLyP-1 and U87MG cells and in vivo biodistribution of FAM-tLyP-1 in a U87MG glioblastoma xenograft model (nude mouse) were determined. The in vivo biodistribution of 18F-tLyP-1 was also determined by microPET/CT.
  
  
  RESULTS
  In vitro, FAM-tLyP-1 was strongly taken up by U87MG cells at very low concentrations (1 μM). In vivo, FAM-tLyP-1 accumulated in glioma (U87MG) tumors, but uptake was minimal in the normal brain tissue 1 h after administration. The distribution of FAM-tLyP-1 in the tumor tissue was consistent with expression of NRP1. The tumor/brain fluorescence intensity ratio in mice treated with FAM-tLyP-1 was significantly higher than the control FAM-labeled peptide 1 h after administration (3.44 ± 0.83 vs. 1.32 ± 0.15; t = 5.547, P = 0.001). Uptake of FAM-tLyP-1 in glioma tumors could be blocked by administering an excess of non-conjugated tLyP-1 peptide. [Lys4] tLyP-1 was labeled with 18F to synthesis a PET (18F-tLyP-1). MicroPET/CT imaging showed the tumor was visualized clearly with a high tumor/brain radiolabel ratio at 60 min (2.69 ± 0.52) and 120 min (3.11 ± 0.25).
  
  
  CONCLUSIONS
  Taken together, our results suggest that tLyP-1 could be developed as a novel fluorescent or radio labelled tracer for imaging glioma.
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hu-bing
authors.initials: HB
authors.lastname: Wu
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Quan-shi
authors.initials: QS
authors.lastname: Wang
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yan-jian
authors.initials: YJ
authors.lastname: Han
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Wen-lan
authors.initials: WL
authors.lastname: Zhou
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hong-sheng
authors.initials: HS
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D005462:Fluorine Radioisotopes; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008024:Ligands; D008297:Male; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D039921:Neuropilins / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D049268:Positron-Emission Tomography; D013194:Staining and Labeling; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D005452:Fluoresceins; D005462:Fluorine Radioisotopes; D008024:Ligands; C533969:LyP-1 peptide; D039921:Neuropilins; D010456:Peptides, Cyclic; C045132:4-carboxyfluorescein