title: Development of tumor-targeted near infrared probes for fluorescence guided surgery.
abstract: Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.
authors: Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
authors: Lindsay E
authors: LE
authors: Kelderhouse
authors: Venkatesh
authors: V
authors: Chelvam
authors: Charity
authors: C
authors: Wayua
authors: Sakkarapalayam
authors: S
authors: Mahalingam
authors: Scott
authors: S
authors: Poh
authors: Sumith A
authors: SA
authors: Kularatne
authors: Philip S
authors: PS
authors: Low
mesh_terms: D000818:Animals; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D005977:Glutarates / Q000737:chemistry; D006801:Humans; D007259:Infrared Rays; D007624:KB Cells; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis*; D051379:Mice; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D009369:Neoplasms / Q000175:diagnosis* / Q000601:surgery*; D014407:Tumor Cells, Cultured; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: C544380:2-(3-(1,3-dicarboxypropyl)ureido)pentanedioic acid; D005456:Fluorescent Dyes; D005977:Glutarates; D014508:Urea; D005492:Folic Acid