title: Synthesis of Tumor-avid Photosensitizer-Gd(III)DTPA conjugates: impact of the number of gadolinium units in T1/T2 relaxivity, intracellular localization, and photosensitizing efficacy.
abstract: To develop novel bifunctional agents for tumor imaging (MR) and photodynamic therapy (PDT), certain tumor-avid photosensitizers derived from chlorophyll-a were conjugated with variable number of Gd(III)aminobenzyl DTPA moieties. All the conjugates containing three or six gadolinium units showed significant T(1) and T(2) relaxivities. However, as a bifunctional agent, the 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) containing 3Gd(III) aminophenyl DTPA was most promising with possible applications in tumor-imaging and PDT. Compared to HPPH, the corresponding 3- and 6Gd(III)aminobenzyl DTPA conjugates exhibited similar electronic absorption characteristics with a slightly decreased intensity of the absorption band at 660 nm. However, compared to HPPH, the excitation of the broad "Soret" band (near 400 nm) of the corresponding 3Gd(III)aminobenzyl-DTPA analogues showed a significant decrease in the fluorescence intensity at 667 nm.
authors.affiliation: PDT Center, Cell Stress Biology, Preclinical Imaging Facility, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Lalit N
authors.initials: LN
authors.lastname: Goswami
authors.forename: William H
authors.initials: WH
authors.lastname: White
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Spernyak
authors.forename: Manivannan
authors.initials: M
authors.lastname: Ethirajan
authors.forename: Yihui
authors.initials: Y
authors.lastname: Chen
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Missert
authors.forename: Janet
authors.initials: J
authors.lastname: Morgan
authors.forename: Richard
authors.initials: R
authors.lastname: Mazurchuk
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Pandey
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019786:Gadolinium DTPA / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D017319:Photosensitizing Agents; D019786:Gadolinium DTPA
references.citation: Eur J Cancer. 1992;28A(8-9):1452-8
references.pmid: 1387543
references.citation: Int J Biochem. 1993 Oct;25(10):1377-83
references.pmid: 8224352
references.citation: Bioconjug Chem. 2005 Jan-Feb;16(1):32-42
references.pmid: 15656573
references.citation: Int J Cancer. 1994 Sep 15;58(6):865-70
references.pmid: 7927880
references.citation: Bioconjug Chem. 2007 Mar-Apr;18(2):410-20
references.pmid: 17279788
references.citation: J Med Chem. 2009 Jul 23;52(14):4306-18
references.pmid: 19507863
references.citation: Bioconjug Chem. 2005 Sep-Oct;16(5):1264-74
references.pmid: 16173807
references.citation: World J Surg Oncol. 2008 Jan 10;6:1
references.pmid: 18186915
references.citation: J Med Chem. 2005 Oct 6;48(20):6286-95
references.pmid: 16190755
references.citation: Lasers Surg Med. 2006 Jun;38(5):445-67
references.pmid: 16788930
references.citation: Adv Drug Deliv Rev. 2001 Jul 2;49(1-2):71-86
references.pmid: 11377804
references.citation: Bioconjug Chem. 2010 May 19;21(5):828-35
references.pmid: 20387862
references.citation: Photochem Photobiol. 1996 Jul;64(1):194-204
references.pmid: 8787014
references.citation: Photochem Photobiol Sci. 2007 Dec;6(12):1257-67
references.pmid: 18046480
references.citation: Lasers Surg Med. 2006 Jun;38(5):364-70
references.pmid: 16788932
references.citation: Photochem Photobiol. 2000 Jul;72(1):94-102
references.pmid: 10911733
references.citation: Cancer Res. 2003 Apr 15;63(8):1806-13
references.pmid: 12702566
references.citation: Methods Enzymol. 2000;319:376-400
references.pmid: 10907528
references.citation: Photochem Photobiol. 2001 Aug;74(2):318-22
references.pmid: 11547571
references.citation: Chem Rev. 1999 Sep 8;99(9):2293-352
references.pmid: 11749483
references.citation: Cancer Res. 1997 Sep 15;57(18):4000-7
references.pmid: 9307285
references.citation: Photochem Photobiol. 2002 Mar;75(3):282-8
references.pmid: 11950094
references.citation: J Biomed Opt. 2005 Sep-Oct;10(5):051503
references.pmid: 16292947
references.citation: Cancer Chemother Pharmacol. 2006 Jan;57(1):40-5
references.pmid: 16001178
references.citation: Photochem Photobiol. 1997 Mar;65(3):389-96
references.pmid: 9077118
references.citation: J Med Chem. 2001 May 10;44(10):1540-59
references.pmid: 11334564