Bacteriochlorophyll- a as photosensitizer for photodynamic treatment of transplantable murine tumors

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 1991-09, Vol.10 (4), p.303-313
• Main Authors: Henderson, Barbara W., Sumlin, Adam B., Owczarczak, Barbara L., Dougherty, Thomas J.
• Format: Article
• Language: English
• Subjects: Animals; bacteria; bacteriochlorophyll 2; bacteriochlorophyll- a; Bacteriochlorophylls - therapeutic use; bacteriopheophytin- a; Biological and medical sciences; Cell Survival - radiation effects; Dose-Response Relationship, Radiation; Fibrosarcoma - drug therapy; Fundamental and applied biological sciences. Psychology; Light; Mammary Neoplasms, Experimental - drug therapy; Mice; Mice, Inbred C3H; Mice, Inbred DBA; Microcirculation - drug effects; Microcirculation - radiation effects; Molecular and cellular biology; Neoplasms, Radiation-Induced - drug therapy; Photochemotherapy; Photodynamic therapy; photosensitization; Radiation-Sensitizing Agents - therapeutic use; Sarcoma, Experimental - drug therapy; Skin - blood supply; transplantable mouse tumor photosensitization; treatment; tumours; Ultraviolet Rays
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/1011-1344(91)80016-B

Bacteriochlorophyll- a (bChl a), which absorbs light of 780 nm wavelength, was tested for in vivo photodynamic activity in the SMT-F and RIF transplantable mouse tumor systems. High performance liquid chromatography (HPLC) analysis of tissue extracts showed that bChl a was rapidly degraded in vivo to bacteriopheophytin- a (bPheo a) and other breakdown products. These were also photodynamically active, and tumor response could be achieved over a wavelength range of 660 to 780 nm, while tumor cure was restricted to wavelengths of 755 (bPheo a) to 780 nm. A photosensitizing product absorbing at 660 nm was also present in isolated tumor cells. Photodynamic cell kill of tumor cells isolated from tumors after bChl a accumulation in vivo, using 755 or 780 nm light vitro, was exponential up to 20–40 J cm −2. Above this light dose little or no further damage could be achieved, which is an indication of the rapid photobleaching of these sensitizers. In vivo, vascular occlusion occurred readily if light treatment was delivered shortly after sensitizer administration, but was delayed if light treatment was carried out 24 h after injection. Although up to 70% of tumor cells were lethally damaged after completion of in vivo light treatment, concurrent severe vascular destruction seemed necessary for tumor cure. Normal tissue photosensitivity totally subsided within 5 days after sensitizer administration.