[Uptake and distribution of hematoporphyrin derivatives (HPD) in arteriosclerotic and normal vessel segments]

Percutaneous treatment of vascular disease is limited by a relatively high long-term restenosis rate. Proliferation of smooth muscle cells may be one of the major reasons for restenosis. Therefore, due to its selective cytotoxic effect, photodynamic therapy (PDT) with HPD-injection and local laser light-application might be a promising therapeutic principle as prophylaxis of restenosis. Up to now, PDT has been used clinically in the treatment of superficial tumors. We studied its potential application as an antiproliferative modality for restenosis prophylaxis. Basic conditions for therapeutic use are: uptake of HPD in arteriosclerotic vessels; arteriosclerotic lesions show a higher photosensitivity than normal vessel after application of HPD. We investigated the uptake of HPD (Photofrin II) in normal (n = 15) and arteriosclerotic (primary lesions n = 52; restenosis n = 10) human vessel segments using quantitative fluorescence detection after incubation with 2.5 micrograms and 5 micrograms HPD/ml cell culture medium. HPD content, as reflected by fluorescence intensity, was measured after 15, 30, 60 min, and 24 h of incubation. Fluorescence intensity was concentration-dependent, with 80% of the maximal uptake reached at 1 h. A preferential uptake of HPD was measured in arteriosclerotic as compared to normal vessel segments (primary lesion: fluorescence-ratio of 3:1 at 1 h; restenosed lesion: fluorescence-ratio of 4:1 at 1 h). In addition, highly cellular plaque segments like restenosed material showed markedly increased fluorescence as compared to acellular matrix. Uptake of HPD was quickly (within 1 h) and preferentially detected in arteriosclerotic segments. A selective cytotoxic effect when combined with laser light may result and could be applied to restenosis prophylaxis.