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 T1 and T2 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 analogs showed a significant decrease in the fluorescence intensity at 667 nm, which was further diminished by increasing the number of Gd(III)units.