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

Abstract

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 ⁶⁸Ga/1,4,7,10-tetraazocyclododecane-<i>N</i>,<i>N</i>′<i>N</i>″,<i>N</i>′″-tetraacetic acid (DOTA) or ⁶⁴Cu/1,4,7-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 ⁶⁸Ga (<i>t</i>_1/2 = 68 min) and ⁶⁴Cu (<i>t</i>_1/2 = 12.7 h) was performed at 100 °C for 15 min with >90% efficiency for all conjugates. <i>In vitro</i> plasma stability assays demonstrated high stability of the ⁶⁴Cu/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and reasonably high stability of the ⁶⁸Ga/DOTA-ZnPc conjugate, which released up to 7% of free ⁶⁸Ga over a 3 h period. Based on <i>in vitro</i> plasma stability results, we performed biodistribution studies on two ⁶⁴Cu-labeled derivatives, which allowed us to select a single candidate for preliminary <i>in vivo</i> experiments. Fluorescence and PET imaging confirmed the potential of these novel conjugates to act as bimodal probes