The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma.
OBJECTIVE
To assess the effect of whole-bladder photodynamic therapy (PDT) on a rat model with orthotopic superficial bladder cancer, as PDT is an alternative intravesical therapy for treating superficial bladder cancer, based on an interaction between a photosensitizer and light energy to induce oxygen radicals that destroy tissue by lipid peroxidation.


METHODS
In all, 76 female Fischer F344 rats were inoculated intravesically with AY-27 tumour cells. After establishing superficial tumour, 24 rats were treated with PDT using aminolaevulinic acid (ALA)-induced protoporphyrin IX as a photosensitizer, and a continuous-wave argon pumped-dye laser (638 nm). At 4 h after intravenous (300 mg/kg) or intravesical (100 mg/mL) administration of ALA the bladders were intravesically exposed to a 40 J/cm(2) light dose; 12 rats received no ALA but were exposed to the same light dose. Before administering ALA, urine cytology samples were taken for analysis. At 3 or 21 days the treated rats were killed and morphological changes in the bladder walls analysed by light microscopy. Forty rats served as controls to examine the presence of tumour.


RESULTS
The tumour established in 33 of 40 rats (83%) in the controls, but after PDT with intravesical ALA there was carcinoma in only in one of 12 (P < 0.001, Pearson's chi(2) test). After PDT with intravenous ALA there was carcinoma in five of 11 rats (P = 0.063, Pearson's chi2 test). In the control group of 12 rats receiving only light energy there was carcinoma in three (P = 0.001, Pearson's chi(2) test). Histologically, at 3 days after PDT there was only mild superficial damage in all six rats treated intravesically. Bladder wall destruction reached the muscular layer, with an abscess in one of six rats treated intravenously. After 3 weeks of PDT there was muscular necrosis with perforation and abscess from catheterization two of six rats treated intravesically and in three the bladder wall totally recovered. In the intravenous group the bladder walls were normal or had only mild superficial damage. Cytology of the urine sediment failed to detect half the tumours in the treatment groups.


CONCLUSIONS
These results support the use of PDT with intravesical ALA-induced protoporphyrin X for treating superficial bladder carcinoma. Intravesical was better than intravenous ALA in eradicating bladder carcinoma with PDT.
Grönlund-Pakkanen
S
S
Department of Surgery, Kuopio University Hospital, Kuopio, Finland. Sari.Gronlund-Pakkanen@kuh.fi
Wahlfors
J
J
Talja
M
M
Kosma
V-M
VM
Pakkanen
T M
TM
Ala-Opas
M
M
Alhava
E
E
Moore
R B
RB
D000283:Administration, Intravesical; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D007262:Infusions, Intravenous; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011524:Protoporphyrins / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D001743:Urinary Bladder / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid