title: Evaluation of polymethine dyes as potential probes for near infrared fluorescence imaging of tumors: part - 1.
abstract: Near-infrared (NIR) organic dyes have become important for many biomedical applications, including in vivo optical imaging. Conjugation of NIR fluorescent dyes to photosensitizing molecules (photosensitizers) holds strong potential for NIR fluorescence image guided photodynamic therapy (PDT) of cancer. Therefore, we were interested in investigating the photophysical properties, in vivo tumor-affinity and fluorescence imaging potential of a series of heterocyclic polymethine dyes, which could then be conjugated to certain PDT agents. For our present study, we selected a series of symmetrical polymethine dyes containing a variety of bis-N-substituted indole or benzindole moieties linked by linear conjugation with and without a fused substituted cyclohexene ring. The N-alkyl side chain at the C-terminal position was functionalized with sulfonic, carboxylic acid, methyl ester or hydroxyl groups. Although, among the parent cyanine dyes investigated, the commercially available, cyanine dye IR783 (3) (bis-indole-N-butylsulfonate)-polymethine dye with a cyclic chloro-cyclohexene moiety showed best fluorescence-imaging ability, based on its spectral properties (λAbs=782 nm, λFl=810 nm, ε = 261,000 M(-1)cm(-1), ΦFl≈0.08) and tumor affinity. In addition to 3, parent dyes IR820 and Cypate (6) were also selected and subjected to further modifications by introducing desired functional groups, which could enable further conjugation of the cyanine dyes to an effective photosensitizer HPPH developed in our laboratory. The synthesis and biological studies (tumor-imaging and PDT) of the resulting bifunctional conjugates are discussed in succeeding paper (Part-2 of this study).
authors.affiliation: 1. Department of Molecular and Cellular Biophysics and Biochemistry, Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263;
authors.forename: Nadine S
authors.initials: NS
authors.lastname: James
authors.forename: Yihui
authors.initials: Y
authors.lastname: Chen
authors.forename: Penny
authors.initials: P
authors.lastname: Joshi
authors.forename: Tymish Y
authors.initials: TY
authors.lastname: Ohulchanskyy
authors.forename: Manivannan
authors.initials: M
authors.lastname: Ethirajan
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
authors.forename: Lucjan
authors.initials: L
authors.lastname: Strekowsk
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Pandey
mesh_terms: D005456:Fluorescent Dyes / Q000138:chemical synthesis*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis*; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*; D061848:Optical Imaging / Q000379:methods*; D010338:Pathology, Clinical / Q000379:methods*; D013194:Staining and Labeling / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D007211:Indoles; C098209:VPM chloride
keywords: Fluorescence Quantum Yields.; Near Infrared Fluorescence Imaging; Near Infrared Fluorophores; Photodynamic therapy; Reactive Oxygen Species
references.citation: Cancer Res. 2004 Nov 1;64(21):8009-14
references.pmid: 15520209
references.citation: Org Lett. 2004 Jun 10;6(12):2067-70
references.pmid: 15176820
references.citation: Bioconjug Chem. 2005 Sep-Oct;16(5):1264-74
references.pmid: 16173807
references.citation: Opt Lett. 2003 Nov 1;28(21):2070-2
references.pmid: 14587818
references.citation: Bioconjug Chem. 2005 Jan-Feb;16(1):51-61
references.pmid: 15656575
references.citation: Cancer Res. 2007 Jul 15;67(14):6882-8
references.pmid: 17638899
references.citation: Clin Cancer Res. 2010 May 15;16(10):2833-44
references.pmid: 20410058
references.citation: Chembiochem. 2008 May 5;9(7):1034-9
references.pmid: 18383057
references.citation: Chembiochem. 2002 Aug 2;3(8):784-6
references.pmid: 12203978
references.citation: Nat Med. 2003 Jan;9(1):123-8
references.pmid: 12514725
references.citation: Lasers Surg Med. 2011 Sep;43(7):705-12
references.pmid: 22057498
references.citation: Phys Med Biol. 1978 Jan;23(1):159-63
references.pmid: 635011
references.citation: Clin Cancer Res. 2007 Jun 15;13(12):3490-7
references.pmid: 17575211
references.citation: Nat Biotechnol. 2005 Mar;23(3):313-20
references.pmid: 15765087
references.citation: Nano Lett. 2007 Sep;7(9):2835-42
references.pmid: 17718587
references.citation: Curr Mol Med. 2004 Jun;4(4):419-30
references.pmid: 15354872
references.citation: Invest Radiol. 2000 Aug;35(8):479-85
references.pmid: 10946975
references.citation: Bioconjug Chem. 2003 May-Jun;14(3):539-45
references.pmid: 12757377
references.citation: Bioconjug Chem. 2007 Jul-Aug;18(4):1303-17
references.pmid: 17583926