~(68)Ga/DOTA- and ~(64)Cu/NOTA-Phthalocyanine Conjugates as Fluorescent/PET Bimodal Imaging Probes

摘要

In this paper, we describe the synthesis and characterization of a series of new bimodal probes combining water-soluble sulfonated zinc phthalocyanine (ZnPc) as a fluorescence imaging unit and either ~(68)Ga/1,4,7,10-tetraazocy-clododecane-N,N'N",N"'-tetraacetic acid (DOTA) or ~(64)Cu/ l,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for PET imaging. The two moieties were linked through aliphatic chains of different lengths to modulate amphiphilicity. Labeling of DOTA- or NOTA-ZnPc conjugates with ~(68)Ga (t_(1/2) = 68 min) and ~(64)Cu (t_(1/2) = 12.7 h) was performed at 100 °C for IS min with >90% efficiency for all conjugates. In vitro plasma stability assays demonstrated high stability of the ~(64)Cu/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and reasonably high stability of the ~(68)Ga/DOTA-ZnPc conjugate, which released up to 7% of free ~(68)Ga over a 3 h period. Based on in vitro plasma stability results, we performed biodistribution studies on two ~(64)Cu-labeled derivatives, which allowed us to select a single candidate for preliminary in vivo experiments. Fluorescence and PET imaging confirmed the potential of these novel conjugates to act as bimodal probes.