title: Asymmetric Rhodamine-Based Fluorescent Probe for Multicolour In Vivo Imaging.
abstract: To achieve rapid and sensitive detection of cancer, activatable fluorescent probes targeting proteases that are overexpressed in various types of cancer have been developed, based on the hydroxymethyl rhodamine green (HMRG) scaffold. However, to visualize altered activities of multiple enzymes in cancer sites, other scaffolds with distinct fluorescence properties from those of HMRG are needed. A novel asymmetrically modified rhodamine with suitable absorption/emission, brightness and equilibrium constant of intramolecular spirocyclization, working in the yellow/orange region, is introduced. As a proof of concept, a probe targeting γ-glutamyl transpeptidase (gGlu-HMJCR) was developed on the basis of the new scaffold. Simultaneous visualization and discrimination of tumours expressing γ-glutamyl transpeptidase (with gGlu-HMJCR) and cathepsins (with Z-Phe-Arg-HMRG) by colour were achieved in a mouse model in vivo.
authors.affiliation: Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan), Fax: (+81) 3-5841-3563.
authors.forename: Ryu J
authors.initials: RJ
authors.lastname: Iwatate
authors.affiliation: Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan), Fax: (+81) 3-5841-3563.|PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Kamiya
authors.affiliation: Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan), Fax: (+81) 3-5841-3563. uranokun@m.u-tokyo.ac.jp.|Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. uranokun@m.u-tokyo.ac.jp.|CREST, Japan Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, Japan. uranokun@m.u-tokyo.ac.jp.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Urano
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000737:chemistry* / Q000378:metabolism; D003952:Diagnostic Imaging; D004151:Dipeptides / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology*; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry*; D005723:gamma-Glutamyltransferase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004151:Dipeptides; D005456:Fluorescent Dyes; D015335:Molecular Probes; D012235:Rhodamines; D013141:Spiro Compounds; C048251:phenylalanylarginine; D005723:gamma-Glutamyltransferase; D002403:Cathepsins; D010447:Peptide Hydrolases
keywords: cancer; cyclization; enzymes; fluorescent probes; in vivo imaging