Photodynamic therapy with PAD-S31, a new hydrophilic chlorin photosensitizer, in an orthotopic rat bladder tumor model.
OBJECTIVE
PAD-S31 (13,17-bis (1-carboxypropion) carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl-porphyrin sodium) (Photochemical Co., Ltd., Okayama, Japan), 1 of the latest second-generation photosensitizers, has hydrophilic characteristics and excitation wavelengths of around 670 nm. Using an orthotopic rat bladder tumor model we investigated the biodistribution of PAD-S31 and assessed the antitumor effects of photodynamic therapy (PDT) with PAD-S31.


METHODS
An orthotopic rat bladder tumor was established by implanting AY-27 cells in the bladder wall. After intravenous PAD-S31 administration the accumulation of PAD-S31 in the tumor and normal bladder wall was investigated by a fluorometric technique. One or 3 hours after intravenous administration of PAD-S31 (5 mg/kg) bladder tumors in rats were transurethrally irradiated at 100 mW/cm with a light dose of 50 to 200 J/cm. The efficacy of PDT was evaluated 7 days later by observation with an ultrathin cystoscope and histopathological examination.


RESULTS
The ratio of PAD-S31 concentration in tumor tissue to that in normal bladder wall was more than 1 at all time points and it achieved a maximum (more than 10) 150 to 240 minutes after PAD-S31 administration. All rats that were irradiated at 100 J/cm 3 hours after PAD-S31 administration showed more than 50% tumor destruction. When the light dose was more than 150 J/cm, more than half of the rats showed complete tumor eradication, of which the average size was 6 mm.


CONCLUSIONS
We report that PDT using PAD-S31 is effective for destroying bladder tumors in an orthotopic rat model. These experimental results suggest that this therapy could be a clinically promising method for the treatment of patients with bladder cancer.
Asanuma
Hiroshi
H
Department of Urology, School of Medicine, Faculty of Science and Technology, Keio University, Tokyo, Japan.
Arai
Tsunenori
T
Morimoto
Yuji
Y
Kawauchi
Satoko
S
Satoh
Hiroyuki
H
Seguchi
Kenji
K
Kikuchi
Makoto
M
Murai
Masaru
M
D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D008297:Male; D009374:Neoplasms, Experimental; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology*; D011829:Radiation Dosage; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
C446480:13,17-bis(1-carboxypropionyl)carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl porphyrin; D017319:Photosensitizing Agents; D011166:Porphyrins