title: Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate.
abstract: Fluorescence optical imaging technologies are currently being developed to image specific molecular targets in vivo. Detection technologies range from those providing microscopic detail to whole body imaging systems with potential clinical use. A number of target-specific near-infrared imaging probes have recently been developed to image receptors, antigens, and enzymes. The goal of the current study was to evaluate a new near-infrared (NIR) folate receptor (FR)-targeted imaging probe for its ability to improve detection of FR-positive cancers. We hypothesized that modification of folate would retain receptor affinity in vivo, despite the bulkier NIR fluorochrome, NIR2 (em = 682 nm). Cellular uptake of the NIR conjugates was significantly higher in FR-positive nasopharyngeal epidermoid carcinoma, KB cells, compared to FR-negative human fibrosarcoma, HT1080 cells. When tumors were implanted in vivo, equal-sized KB tumors showed a 2.4-fold higher signal intensity compared to HT1080 tumors (24 h). The maximum signal-to-background ratio (3-fold) was observed at 24 h in KB tumor. Injection of the unmodified NIR2 fluorochrome did not result in persistent contrast increases under similar conditions. Furthermore, tumor enhancement with the NIR2-folate probe persisted over 48 h and was inhibitable in vivo by administration of unlabeled folate. These results indicate that folate-modified NIR fluorochrome conjugate can be used for improved detection of FR-positive tumors.
authors.affiliation: Center for Molecular Imaging Research,Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Moon
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Lin
authors.forename: Terence
authors.initials: T
authors.lastname: O'Loughlin
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.forename: Dong-Eog
authors.initials: DE
authors.lastname: Kim
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Tung
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D002352:Carrier Proteins; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid