Microlocalization of lipophilic porphyrins: Non-toxic enhancers of boron neutron-capture therapy

Abstract

Purpose: To compare the macroscopic and microscopic distributions of the novel non-toxic lipophilic porphyrins copper (II) 5,10,15,20-tetrakis-(3-[1,2 dicarba-closo-dodecaboranyl]methoxyphenyl)-porphyrin (CuTCPH), potentially useful for boron neutron-capture therapy (BNCT), with those of its zinc fluorescent congener zinc (II) 5,10,15,20-tetrakis-(3-[1,2 dicarba-closo-dodecaboranyl]methoxyphenyl)-porphyrin (ZnTCPH) in tissues of tumor-bearing mice.Materials and methods: ZnTCPH and CuTCPH were synthesized, then injected intraperitoneally (ip) into tumor-bearing mice. Macroscopic biodistribution was assessed by determining average boron concentrations in tumor, blood, brain, skin, and liver using atomic-emission spectrometry. The euthanized mice and their vital organs were photographed first under an ultraviolet lamp and then under a bright fluorescent lamp. Thin sections of liver and tumor were analyzed by confocal fluorescence microscopy (CFM).Results: ZnTCPH-injected, but not CuTCPH-injected mice bearing subcutaneous tumors showed fluorescence from liver, spleen and tumors. Macrodistributions of boron in various tissues were similar in mice whether injected with ZnTCPH or CuTCPH. CFM of unfixed liver sections showed cytoplasmic fluorescence from Kupffer cells in a periportal lobular distribution evenly throughout the liver. In the tumors studied, such fluorescence was also cytoplasmic but unlike liver fluorescence, was macroscopically heterogeneous.Conclusion: ZnTCPH serves as a useful fluorescent experimental surrogate for CuTCPH to delineate its macroscopic and microscopic distributions in organs and tumors.