Enhanced tumour selectivity of photodynamic therapy in the rat colon using a radioprotective agent.
Radioprotective agents have been found to protect normal tissues during photodynamic therapy (PDT). We have investigated a phosphorylated thiol protectant WR-77913 (W7) with the photosensitizer aluminium sulphonated phthalocyanine (AISPc). We compared the effects of PDT on normal and tumour tissue in the rat colon, with and without this protectant. In normal colon no necrosis was seen in sites treated after administration of the W7. Necrosis of mean diameter 4.2 mm was seen in those given the protectant after light exposure. At tumour sites the area of necrosis was similar after light exposure before and after the administration of the protective agent. These results suggest a possible role for W7 in enhancement of selectivity of PDT action. Several mechanisms of protection against porphyrin phototoxicity by these drugs have been proposed, including acceleration of photobleaching. We used fluorescence to detect AISPc in strips of rat colon before and after laser treatment, with and without W7. However, a primary role for the photobleaching of AISPc as the mechanism for the protection shown is not supported by these observations.
Bedwell
J
J
Department of Surgery, University College London, UK.
Chatlani
P T
PT
MacRobert
A J
AJ
Roberts
J E
JE
Barr
H
H
Dillon
J
J
Bown
S G
SG
D000535:Aluminum / Q000627:therapeutic use* / Q000633:toxicity; D004999:Amifostine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D007211:Indoles / Q000627:therapeutic use* / Q000633:toxicity; D053685:Laser Therapy; D008027:Light; D009336:Necrosis; D009942:Organometallic Compounds / Q000627:therapeutic use* / Q000633:toxicity; D010778:Photochemotherapy; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats
D007211:Indoles; D009942:Organometallic Compounds; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; C035284:WR 77913; D000535:Aluminum; D004999:Amifostine