Synthesis of a novel L-methyl-methionine-ICG-Der-02 fluorescent probe for in vivo near infrared imaging of tumors.

Abstract

PURPOSE:

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.

METHOD:

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.

CONCLUSION:

Met-ICG-Der-02 probe is a promising optical imaging agent for tumor diagnosis, especially in their early stage.

• Authors: Didel M Mahounga, Lingling Shan, Cao Jie, Changli Du, Shunan Wan, Yueqing Gu
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 14 Issue 6 Pg. 699-707 (Dec 2012) ISSN: 1860-2002 [Electronic] United States
• PMID: 22552743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Transport System y+
• Carbocyanines
• Fluorescent Dyes
• Large Neutral Amino Acid-Transporter 1
• methylmethionine ICG-Der-02
• Methionine
• Indocyanine Green

Topics

• Amino Acid Transport System y+
• Animals
• Carbocyanines (chemical synthesis, chemistry, toxicity)
• Cell Death (drug effects)
• Cell Line, Tumor
• Diagnostic Imaging
• Fluorescent Dyes (chemical synthesis, chemistry, toxicity)
• Humans
• Indocyanine Green (chemical synthesis, chemistry, toxicity)
• Large Neutral Amino Acid-Transporter 1
• Male
• Methionine (analogs & derivatives, chemical synthesis, chemistry, toxicity)
• Mice
• Mice, Nude
• Neoplasms (diagnosis)
• Reference Standards
• Spectroscopy, Near-Infrared
• Xenograft Model Antitumor Assays