Synthesis, characterization and evaluation of a Cu-labeled macrocyclic-porphyrin as a potential chelator for 64Cu-based radiopharmaceuticals

Synthesis of 5-(4-aminophenyl)-10,15,20-triphenyl porphyrin (B) was performed using the Lindsey method and characterized by H-1 NMR. Cu-porphyrin complexation conditions were tested using Cu-nat and UV-Vis analysis confirmed metallation. High specific activity Cu-64 was produced via cyclotron using the Ni-64(p,n) reaction. For radiolabeling, (CuCl2)-Cu-64 dissolved in acetate buffer (pH 5.6) was mixed with compound (B) in DMSO, and incubated for 60min at 37 degrees C, obtaining a labeling yield>95% at 60min. The labeled complex [Cu-64]-5-(4-aminophenyl)-10,15,20-triphenyl porphyrin (C) showed good stability (>95%) for up 48h when incubated in human serum. MicroPET images were acquired in rats and mice using Cu-64-porphyrin (C) and (CuCl2)-Cu-64 in order to compare their biodistribution. Results suggest that (C) is an excellent candidate to prepare stable metal complexes suitable for the development of novel Cu-64-based radiopharmaceuticals using biological moieties to target specific receptors.