<sup>68</sup>Ga/DOTA- and <sup>64</sup>Cu/NOTA-Phthalocyanine
Conjugates as Fluorescent/PET Bimodal Imaging Probes
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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 <sup>68</sup>Ga/1,4,7,10-tetraazocyclododecane-<i>N</i>,<i>N</i>′<i>N</i>″,<i>N</i>′″-tetraacetic
acid (DOTA) or <sup>64</sup>Cu/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 <sup>68</sup>Ga (<i>t</i><sub>1/2</sub> = 68 min) and <sup>64</sup>Cu (<i>t</i><sub>1/2</sub> = 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 <sup>64</sup>Cu/NOTA-ZnPc conjugate, which remained intact
over a 24 h time period, and reasonably high stability of the <sup>68</sup>Ga/DOTA-ZnPc conjugate, which released up to 7% of free <sup>68</sup>Ga over a 3 h period. Based on <i>in vitro</i> plasma
stability results, we performed biodistribution studies on two <sup>64</sup>Cu-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