Whole bladder photodynamic therapy for orthotopic superficial bladder cancer in rats: a study of intravenous and intravesical administration of photosensitizers.
OBJECTIVE
Photodynamic therapy after intravenous injection of Photofrin (QLT Phototherapeutics, Vancouver, British Columbia, Canada) results in a contracted bladder and skin photosensitivity, which limits its clinical application. In an attempt to overcome these limitations photodynamic therapy after intravesical instillation of Photofrin or 5-aminolevulinic acid (ALA) in an orthotopic rat bladder tumor model was explored and compared with intravenous Photofrin for photodynamic therapy efficacy and phototoxicity.


METHODS
At 2 weeks after bladder implantation of 1.5 x 10(6) AY-27 tumor cells animals were randomly grouped. Photofrin was administered (5 mg./kg. intravenously and 2 mg./ml. intravesically). The ALA concentration for intravesical instillation was 300 mM. Whole bladder photodynamic therapy with graded doses of light (lambda = 630 nm.) was performed 4 hours after drug administration. Tumor control and complications were evaluated.


RESULTS
Photodynamic therapy with intravenous Photofrin plus 100 J./cm.(2) light resulted in severe bladder damage. Of 10 rats 6 died and 2 of the 10 that received 50 J./cm.(2) died. There were no photodynamic therapy related deaths in groups receiving intravesical instillation of Photofrin or ALA that also received 50 to 100 J./cm.(2) Median survival in rats treated with ALA intravesically plus 75 J./cm.(2) (77 days), Photofrin intravesically plus 50 (67) or 100 J./cm.(2) (76) and Photofrin intravenously plus 50 J./cm.(2) (60) were significantly different from that in controls (44).


CONCLUSIONS
Intravesical instillation of Photofrin or ALA can achieve the same photodynamic therapy efficacy as intravenous Photofrin in this orthotopic rat bladder tumor model with less phototoxicity to normal tissues.
Xiao
Zhengwen
Z
Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
Brown
Kevin
K
Tulip
John
J
Moore
Ronald B
RB
D000283:Administration, Intravesical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D007275:Injections, Intravenous; D009368:Neoplasm Transplantation; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000503:physiopathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; D017323:Dihematoporphyrin Ether