Preclinical Evaluation of Motexafin Lutetium-mediated Intraperitoneal Photodynamic Therapy in a Canine Model
Intraperitoneal photodynamic therapy (IP PDT) is an experimental cancer treatment in clinical development for the treatment of peritoneal carcinomatosis and sarcomatosis. A canine study of motexafin lutetium (Lu-Tex)-mediated IP PDT was performed to evaluate normal tissue toxicities of this treatmen...
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Published in | Clinical cancer research Vol. 7; no. 2; pp. 374 - 381 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.02.2001
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Subjects | |
Online Access | Get full text |
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Summary: | Intraperitoneal photodynamic therapy (IP PDT) is an
experimental cancer treatment in clinical development for the treatment
of peritoneal carcinomatosis and sarcomatosis. A canine study of
motexafin lutetium (Lu-Tex)-mediated IP PDT was performed to evaluate
normal tissue toxicities of this treatment in the presence and absence
of a bowel resection and to assess the feasibility of measuring Lu-Tex
fluorescence in abdominal tissues. Thirteen dogs were treated with
Lu-Tex (0.2–2 mg/kg) i.v. 3 h before laparotomy and 730-nm light
delivery (fluences, 0.5–2.0 J/cm 2 ; average fluence rate<150 mW/cm 2 ). Laparoscopy was performed 7–10 days after
the procedure to assess acute toxicities. In situ
fluorescence spectra were obtained from various abdominal tissues
before and after light delivery using a fiber array probe with
fixed-source detector distances. Lu-Tex-mediated IP PDT was well
tolerated at the doses of drug and light studied. Bowel toxicity was
not observed in animals treated with a bowel resection before PDT. Mild
transient liver function test abnormalities without associated clinical
sequelae were observed. No gross PDT-related abnormalities were
observed at laparoscopy or necropsy; however, thickening in the
glomerular capillary wall and the mesangium were noted microscopically
in the kidneys of seven dogs. No renal function abnormalities were
found. Analysis of the fluorescence spectra from intra-abdominal
tissues suggests that measurements of Lu-Tex in situ are
feasible and may provide a way of assessing photosensitizer
concentration in vivo without the need for a biopsy.
These results support the continued development of Lu-Tex as a
candidate photosensitizer for IP PDT. |
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ISSN: | 1078-0432 1557-3265 |