Photodynamic therapy with PAD-S31, a new hydrophilic chlorin photosensitizer, in an orthotopic rat bladder tumor model

Hiroshi Asanuma, Tsunenori Arai, Yuji Morimoto, Satoko Kawauchi, Hiroyuki Satoh, Kenji Seguchi, Makoto Kikuchi, Masaru Murai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: PAD-S31 (13,17-bis (1-carboxypropion) carbamoylethyl-3-thenyl-8- thoxyiminoethylidene-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 wave-lengths 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. Materials and 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/cm2 with a light dose of 50 to 200 J/cm2. 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/cm2 3 hours after PAD-S31 administration showed more than 50% tumor destruction. When the light dose was more than 150 J/cm 2, 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.

Original languageEnglish
Pages (from-to)2016-2021
Number of pages6
JournalJournal of Urology
Volume174
Issue number5
DOIs
Publication statusPublished - 2005 Nov
Externally publishedYes

Fingerprint

Photosensitizing Agents
Photochemotherapy
Urinary Bladder Neoplasms
Urinary Bladder
Cystoscopes
chlorin
13,17-bis(1-carboxypropionyl)carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl porphyrin
Light
Neoplasms
Porphyrins
Intravenous Administration
Japan
Sodium
Observation

Keywords

  • 13,17-bis(1-carboxypropion)carbamoylethyl-3-ethenyl-8-ethoxjdminoethylidene-7- hydroxy-2,7,12,18-tetramethyl-porphyrin
  • Bladder
  • Bladder neoplasms
  • Photochemotherapy
  • Rats, inbred F344

ASJC Scopus subject areas

  • Urology

Cite this

Photodynamic therapy with PAD-S31, a new hydrophilic chlorin photosensitizer, in an orthotopic rat bladder tumor model. / Asanuma, Hiroshi; Arai, Tsunenori; Morimoto, Yuji; Kawauchi, Satoko; Satoh, Hiroyuki; Seguchi, Kenji; Kikuchi, Makoto; Murai, Masaru.

In: Journal of Urology, Vol. 174, No. 5, 11.2005, p. 2016-2021.

Research output: Contribution to journalArticle

Asanuma, Hiroshi ; Arai, Tsunenori ; Morimoto, Yuji ; Kawauchi, Satoko ; Satoh, Hiroyuki ; Seguchi, Kenji ; Kikuchi, Makoto ; Murai, Masaru. / Photodynamic therapy with PAD-S31, a new hydrophilic chlorin photosensitizer, in an orthotopic rat bladder tumor model. In: Journal of Urology. 2005 ; Vol. 174, No. 5. pp. 2016-2021.
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AU - Arai, Tsunenori

AU - Morimoto, Yuji

AU - Kawauchi, Satoko

AU - Satoh, Hiroyuki

AU - Seguchi, Kenji

AU - Kikuchi, Makoto

AU - Murai, Masaru

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N2 - Purpose: PAD-S31 (13,17-bis (1-carboxypropion) carbamoylethyl-3-thenyl-8- thoxyiminoethylidene-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 wave-lengths 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. Materials and 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/cm2 with a light dose of 50 to 200 J/cm2. 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/cm2 3 hours after PAD-S31 administration showed more than 50% tumor destruction. When the light dose was more than 150 J/cm 2, 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.

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KW - Bladder neoplasms

KW - Photochemotherapy

KW - Rats, inbred F344

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