The vascular response to photodynamic therapy with ATX-S10Na(II) in the normal rat colon.
The mechanism of tissue damage from photodynamic therapy (PDT) may be cellular, vascular or both, depending on the photosensitising agent and the treatment conditions. Well established photosensitisers like porfimer sodium have an optimum drug light interval of two days and may cause skin photosensitivity lasting several weeks. ATX-S10Na(II) is a new photosensitiser that remains largely in the vasculature after systemic administration and clears from the body within a few hours. The present study looks at the factors controlling the extent of PDT necrosis using ATX-S10Na(II) and correlates these with changes in the circulation after PDT. Normal Wistar rats were sensitised with ATX-S10Na(II), 2 mg/kg. At laparotomy, a laser fibre was positioned just touching the colonic mucosa and 50 J light at 670 nm delivered varying the drug light interval (0.5-24 h) and light delivery regime (100 mW continuous, 20 mW continuous or 100 mW in five fractions). Some animals were killed at three days to document the area of necrosis, others received fluorescein shortly prior to death (from a few minutes to three days after PDT) to outline the zone of PDT induced vascular shutdown. Maximum necrosis was seen with the shortest drug light interval (0.5 h), with no effect by 6 h. Fractionating the light or lowering the power did not increase the necrosis. The area of fluorescein exclusion increased over the first 2 h after PDT (in contrast to the re-perfusion seen with other photosensitisers) and correlated with the area of necrosis. PDT with ATX-S10Na(II) is most effective with a drug light interval of less than one hour. It induces irreversible vascular shutdown that extends after completion of light delivery and which is largely independent of the light delivery regime.
Harada
Masahiko
M
National Medical Laser Centre, Academic Division of Surgical Specialties, Royal Free and University College Medical School, 1st Floor, Charles Bell House, 67-73 Riding House Street, London W1W 7EJ, UK.
Woodhams
Josephine
J
MacRobert
Alexander J
AJ
Feneley
Mark R
MR
Kato
Harubumi
H
Bown
Stephen G
SG
D000818:Animals; D003106:Colon / Q000098:blood supply* / Q000187:drug effects* / Q000528:radiation effects; D005452:Fluoresceins; D008856:Microscopy, Fluorescence; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence
C117772:ATX S10Na(II); D005452:Fluoresceins; D017319:Photosensitizing Agents; D011166:Porphyrins