β-conjugation of gadolinium(III) DOTA complexes to zinc(II) porpholactol as potential multimodal imaging contrast agents

Abstract

Synthesis of two bimodal imaging agents consist of a hydrophobic zinc(II) tetrapentafluorophenylporpholactol core and a β-substituted hydrophilic Gd ( III ) DO3A (ZnLGd539) or DOTA (ZnLGd595) like moiety has been described (DO3A = 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Through β-conjugation approach, the absorption at deep red region increases compared to traditional conjugation methods at meso-position. More importantly, these new complexes possess largely improved ionic relaxitivites relative to the sole Gd ( III ) magnetic resonance imaging (MRI) agents such as Gd ( III ) DO3A and Gd ( III ) DOTA like complexes. Combining the optical and magnetic resonance measurements in aqueous media, the largely enhanced r1 relaxivities was attributed to the aggregation of ZnLGd539 and ZnLGd595 in aqueous media. Furthermore, fluorescence and magnetic resonance imaging experiment showed that both ZnLGd539 and ZnLGd595 can be applied as potential bimodal imaging contrast agents. Finally, both compounds showed no dark cytotoxicity and good photocytotoxicity (IC50 = 1.73 ± 0.13 and 1.52 ± 0.10 μM for ZnLGd539 and ZnLGd595 respectively) on Hela cells.