title: Cyanine dyes as contrast agents for near-infrared imaging in vivo: acute tolerance, pharmacokinetics, and fluorescence imaging.
abstract: We compare pharmacokinetic, tolerance, and imaging properties of two near-IR contrast agents, indocyanine green (ICG) and 1,1(')-bis-(4-sulfobutyl) indotricarbocyanine-5,5(')-dicarboxylic acid diglucamide monosodium salt (SIDAG). ICG is a clinically approved imaging agent, and its derivative SIDAG is a more hydrophilic counterpart that has recently shown promising imaging properties in preclinical studies. The rather lipophilic ICG has a very short plasma half-life, thus limiting the time available to image body regions during its vascular circulation (e.g., the breast in optical mammography where scanning over several minutes is required). In order to change the physicochemical properties of the indotricarbocyanine dye backbone, several derivatives were synthesized with increasing hydrophilicity. The most hydrophilic dye SIDAG is selected for further biological characterization. The acute tolerance of SIDAG in mice is increased up to 60-fold compared to ICG. Contrary to ICG, the pharmacokinetic properties of SIDAG are shifted toward renal elimination, caused by the high hydrophilicity of the molecule. N-Nitrosomethylurea (NMU)-induced rat breast carcinomas are clearly demarcated, both immediately and 24 h after intravenous administration of SIDAG, whereas ICG shows a weak tumor contrast under the same conditions. Our findings demonstrate that SIDAG is a high potential contrast agent for optical imaging, which could increase the sensitivity for detection of inflamed regions and tumors.
authors: Physikalisch-Technische Bundesanstalt, Abbestr. 2-12, Berlin, 10587 Germany. bernd.ebert@ptb.de
authors: Bernd
authors: B
authors: Ebert
authors: Björn
authors: B
authors: Riefke
authors: Uwe
authors: U
authors: Sukowski
authors: Kai
authors: K
authors: Licha
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D007091:Image Processing, Computer-Assisted; D007208:Indocyanine Green / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence / Q000379:methods*
chemical_list: C430879:1,1'-bis-(4-sulfobutyl)indotricarbocyanine-5,5'-dicarboxylic acid diglucamide; D002232:Carbocyanines; D003287:Contrast Media; D005456:Fluorescent Dyes; D007208:Indocyanine Green