Selective necrosis in dimethylhydrazine-induced rat colon tumors using phthalocyanine photodynamic therapy.
Photodynamic therapy is a relatively new method for the local destruction of tumors based on the administration of a photosensitizing agent that is retained in tumors and then activated to produce cytotoxic agents following irradiation with light. The selective retention of photosensitizers by dimethylhydrazine-induced colonic tumors over adjacent normal tissue is small (2:1, tumor to normal), making the possibility of producing selective tumor necrosis with total sparing of normal tissue difficult. Colonic cancers and adjacent normal colon were treated with the same light doses from an argon-pumped dye laser 48 h after intravenous injection of 0.5 or 5 mg/kg of the photosensitizer, aluminum-sulfonated phthalocyanine. There was little difference between the amount of necrosis in the tumor and the adjacent normal colon if the injected dose of photosensitizer was 5 mg/kg. However, at the lower dose of 0.5 mg/g, up to 2 mm of necrosis could be produced in the tumor without damaging the normal colon. In vivo fluorescence measurements showed that the photosensitizer was photodegraded during irradiation. This was confirmed by in vitro fluorescence scans of the normal colon after irradiation; the fluorescence from the photosensitizer was lowest at the point of irradiation. It is postulated that at low dosage, selective necrosis can occur because the photosensitizer is photodegraded in the normal colon before a threshold photodynamic dose is reached, whereas in tumor containing twice as much photosensitizer, a photodynamic threshold dose can be achieved and necrosis produced.
Barr
H
H
Rayne Institute, Department of Surgery, University College London, England.
Tralau
C J
CJ
Boulos
P B
PB
MacRobert
A J
AJ
Krasner
N
N
Phillips
D
D
Bown
S G
SG
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004127:Dimethylhydrazines / Q000009:adverse effects*; D005453:Fluorescence; D007211:Indoles / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D007275:Injections, Intravenous; D054833:Isoindoles; D053685:Laser Therapy; D008297:Male; D008763:Methylhydrazines / Q000009:adverse effects*; D009336:Necrosis; D010777:Photochemistry; D010778:Photochemotherapy / Q000379:methods; D010860:Pigments, Biological / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D004127:Dimethylhydrazines; D007211:Indoles; D054833:Isoindoles; D008763:Methylhydrazines; D010860:Pigments, Biological; D019813:1,2-Dimethylhydrazine; C013647:phthalocyanine