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.
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.
Goswami
Lalit N
LN
PDT Center, Cell Stress Biology, Preclinical Imaging Facility, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
White
William H
WH
Spernyak
Joseph A
JA
Ethirajan
Manivannan
M
Chen
Yihui
Y
Missert
Joseph R
JR
Morgan
Janet
J
Mazurchuk
Richard
R
Pandey
Ravindra K
RK
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
D017319:Photosensitizing Agents; D019786:Gadolinium DTPA
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