Biological activities of phthalocyanines. XII: Synthesis tumor uptake and biodistribution of 14C-labeled disulfonated and trisulfonated gallium phthalocyanine in C3H mice

J Photochem Photobiol B. 1990 Jun;6(1-2):121-32. doi: 10.1016/1011-1344(90)85081-7.

Abstract

The biodistribution and metabolism of 14C-labeled disulfonated and trisulfonated gallium phthalocyanine (Ga-PcS) was studied in radiation-induced fibrosarcoma tumor-bearing C3H mice. The [14C]Ga-PcS compounds were prepared via the condensation of [14C]phthalic acid and sulfophthalic acid in the presence of gallium chloride and characterized by their spectroscopic and chromatographic properties. The tissue concentrations of the dyes was measured by scintillation counting of the 14C and by extraction and fluorescence measurements. Elevated dye levels were found in the liver, lungs, kidneys and spleen as well as in the tumor. Lower sulfonation of Ga-PcS favored liver and spleen uptake whereas higher dye sulfonation resulted in greater kidney uptake. Both dyes showed high tumor uptake with peak concentrations exceeding those of most tissues except for the liver in the case of Ga-PcS2. The highest tumor uptake was observed with Ga-PcS3. Both dyes were slowly excreted from the body. The liver-feces pathway was favored in the case of Ga-PcS2 with high activities persisting in the liver, even after 21 days. The Ga-PcS3 was preferentially excreted via the kidney-urine pathway. High performance liquid chromatography analysis of the liver and tumor extracts of [14C]Ga-PcS3-treated animals did not reveal desulfonation of the dye. However, urine analysis showed the presence of radioactive metabolites lacking the characteristic phthalocyanine absorption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Carbon Radioisotopes
  • Female
  • Gallium / pharmacokinetics*
  • Indicators and Reagents
  • Indoles / chemical synthesis
  • Indoles / metabolism
  • Indoles / pharmacokinetics*
  • Mice
  • Mice, Inbred C3H
  • Neoplasms, Experimental / metabolism*
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Radiation-Sensitizing Agents / pharmacokinetics*
  • Radioisotope Dilution Technique
  • Tissue Distribution

Substances

  • Carbon Radioisotopes
  • Indicators and Reagents
  • Indoles
  • Organometallic Compounds
  • Radiation-Sensitizing Agents
  • gallium disulfophthalocyanine
  • gallium trisulfophthalocyanine
  • Gallium