title: Synthesis of a novel L-methyl-methionine-ICG-Der-02 fluorescent probe for in vivo near infrared imaging of tumors.
abstract: OBJECTIVE
  A novel near infrared fluorescent probe, L-methyl-methionine (Met)-ICG-Der-02, was synthesized and characterized for in vivo imaging of tumors and early diagnosis of cancers.
  
  
  METHODS
  Met was conjugated with ICG-Der-02 dye through the amide bond function by ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide catalysis chemistry. Met-ICG-Der-02 probe uptake was evaluated on PC3, MDA-MB-231, and human embryonic lung fibroblast cell lines. The dynamics of Met-ICG-Der-02 was investigated in athymic nude mice prior to evaluation of the probe targeting capability in prostate and breast cancer models.
  
  
  RESULTS
  Met-ICG-Der-02 was successfully synthesized. Cell experiments demonstrated excellent cellular uptake of Met-ICG-Der-02 on cancer cell lines without cytotoxicity. Optical imaging showed a distinguishable fluorescence signal in the tumor area at 2 h while maximal tumor-to-normal tissue contrast ratio was at 12 h Met-ICG-Der-02 post-injection. Additionally, dynamic study of the probe indicated intestinal and liver-kidney clearance pathways.
  
  
  CONCLUSIONS
  Met-ICG-Der-02 probe is a promising optical imaging agent for tumor diagnosis, especially in their early stage.
authors.affiliation: Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Didel M
authors.initials: DM
authors.lastname: Mahounga
authors.forename: Lingling
authors.initials: L
authors.lastname: Shan
authors.forename: Cao
authors.initials: C
authors.lastname: Jie
authors.forename: Changli
authors.initials: C
authors.lastname: Du
authors.forename: Shunan
authors.initials: S
authors.lastname: Wan
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D027182:Amino Acid Transport System y+; D000818:Animals; D002232:Carbocyanines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007208:Indocyanine Green / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D027283:Large Neutral Amino Acid-Transporter 1; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis*; D012015:Reference Standards; D019265:Spectroscopy, Near-Infrared; D023041:Xenograft Model Antitumor Assays
chemical_list: D027182:Amino Acid Transport System y+; D002232:Carbocyanines; D005456:Fluorescent Dyes; D027283:Large Neutral Amino Acid-Transporter 1; C580752:methylmethionine ICG-Der-02; D008715:Methionine; D007208:Indocyanine Green