Cellular levels of photosensitisers in tumours: the role of proximity to the blood supply

Flow cytometry using the tumour perfusion probe Hoechst 33342 was employed to examine the distribution of photosensitisers in tumour cells located at different distances from the blood supply. Two tumour models, the SCCVII squamous cell carcinoma and FsaR fibrosarcoma growing in C3H/HeN mice, were u...

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Bibliographic Details
Published in:British journal of cancer 1994-10, Vol.70 (4), p.604-610
Main Authors: Korbelik, M, Krosl, G
Format: Article
Language:English
Subjects:
Animals
Benzimidazoles - pharmacokinetics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Squamous Cell - blood supply
Carcinoma, Squamous Cell - metabolism
Drug Resistance
Epidemiology
experimental-oncology
Female
Fibrosarcoma - blood supply
Fibrosarcoma - metabolism
Flow Cytometry
Fluorescence
Lasers
Mice
Mice, Inbred C3H
Molecular Medicine
Neoplasm Transplantation
Neoplasms, Experimental - blood supply
Neoplasms, Experimental - metabolism
Oncology
Perfusion
Photochemotherapy
Photosensitizing Agents - metabolism
Photosensitizing Agents - pharmacokinetics
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Summary:Flow cytometry using the tumour perfusion probe Hoechst 33342 was employed to examine the distribution of photosensitisers in tumour cells located at different distances from the blood supply. Two tumour models, the SCCVII squamous cell carcinoma and FsaR fibrosarcoma growing in C3H/HeN mice, were used in the experiments. Among the photosensitisers tested, only BPD (benzoporphyrin derivative monoacid) exhibited uniform distribution in tumour cells irrespective of their distance from the vasculature. In this respect, 5-aminolaevulinic acid (i.e. its metabolite protoporphyrin IX), di- and tetrasulphonated aluminium phthalocyanines (A1PcS2 and AlPcS4), di- and tetrasulphonated tetraphenylporphines (TPPS2 and TPPS4), Photofrin and bacteriochlorophyll-a (i.e. its metabolite bacteriopheophytin-a) followed BPD in decreasing order in their efficacy of accumulation in tumour cells remote from the blood supply. This photosensitiser property appeared not to depend on tumour type, tumour size, route of photosensitiser administration, time after the administration, photosensitiser lipophilicity or on the presence of host cell infiltrate in the tumour. Following treatment with photodynamic therapy (PDT) in vivo, tumour cells were sorted based on their blood vessel proximity and their survival was determined by colony formation assay. The data demonstrate that the direct killing of tumour cells by Photofrin- and A1PcS2-based PDT decreases with increasing distance of the cells from the blood supply.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1994.358