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 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/cm2; average fluence rate <150 mW/cm2). 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.
Department of Surgery, University of Pennsylvania School of Veterinary Medicine, Philadelphia 19104, USA.
G M
GM
Griffin
T
T
Zhu
M
M
Solonenko
F
F
Del Piero
A
A
Kapakin
T M
TM
Busch
A
A
Yodh
G
G
Polin
T
T
Bauer
D
D
Fraker
S M
SM
Hahn
D000005:Abdomen / Q000473:pathology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D010535:Laparoscopy; D008665:Metalloporphyrins / Q000633:toxicity*; D009336:Necrosis; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000633:toxicity*; D016896:Treatment Outcome
D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C102825:motexafin lutetium; C437683:motexafin gadolinium