Biodistribution and tumor uptake of [67Ga]chlorogallium-tetraoctadecyloxy phthalocyanine and its sulfonation products in tumor bearing C3H mice.

To evaluate the biodistribution and tumor uptake of chlorogallium tetraoctadecycloxy phthalocyanine, a potential new drug for the photodynamic therapy of cancer, we prepared the radioactive 67Ga-labeled complex and its water soluble sulfonated derivative. The non-sulfonated dye was obtained by condensation of octadecyloxyphthalonitrile in the presence of a mixture of 67Ga and 69Ga chloride. The sulfonated derivative was obtained by treatment of the condensation product with oleum. As singlet molecular oxygen has been implicated in the photodynamic action of phthalocyanines (Pcs), the quantum yield of singlet oxygen (phi delta) was evaluated for chlorogallium tetraoctadecyloxy Pc, and also its zinc, aluminum and metal free analogues. After intraperitoneal administration of the non-sulfonated dye into RIF tumor bearing C3H mice, a very high 67Ga-uptake was observed in the spleen, while tumor radioactivity remained low during the 3 day study. The in vivo stability of the 67Ga-phthalocyanine complex was confirmed by comparing the distribution pattern with that of 67Ga-citrate, which proved to be significantly different. Intravenous injection of the sulfonated dye resulted in an overall lowering of 67Ga-uptake by most tissues, particularly in the spleen, while tumor radioactivities were slightly higher. These data suggest that amphiphilic photosensitizers, containing both polar sulfonate groups and long aliphatic substituents, exhibit the best distribution pattern for both imaging and photodynamic therapy of tumors.