[Effect of ascorbate on the permeation and photosensitizing activity of hematoporphyrin derivative (HPD) in tumor].

OBJECTIVE

To determine the depth of permeation and concentration of HPD in tumor tissue which had been immersed in HPD in the presence and absence of ascorbic acid, and to examine its photosensitizing effect.

METHODS

Solid S-180 sarcoma of 1 cm3 in size was excised from tumor-bearing mice and immersed in HPD (PsD-007) 1 mg/ml normal saline (group I), or HPD (PsD-007) 1 mg/ml plus ascorbic acid 20 mg/ml normal saline (group II) for 1 hr. For comparison, HPD (PsD-007) 10 mg/kg was injected intravenously to mice bearing tumor of similar size and the tumor was excised 24 hr later(group III).

RESULTS

When the tumors were cross-sectioned and UV (370 nm) irradiated, red fluorescence was mainly at the periphery of tumors that had been immersed in HPD whereas the fluorescence was weaker and more evenly distributed in tumors of mice that had received HPD i.v. Similar features were observed under fluorescence microscope in frozen sections of identically treated tumors. The concentration of PsD-007 (microgram/g) and malondialdehyde (nmol/L) in the tumor homogenates was higher in tumors that had been immersed in PsD-007 plus ascorbate than in tumors immersed in PsD-007 alone. Tumors of mice that had received PsD-007 i.v. had the lowest concentration of both PsD-007 and malondialdehyde.

CONCLUSIONS

Ascorbate facilitates permeation of HPD into tumor and enhances the photo-dynamic effect of HPD.