Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster.
Photodynamic therapy (PDT) has the potential to destroy small tumours with safe healing of adjacent normal tissue. This study looks at the effects of PDT on the normal pancreas and adjacent tissues in hamsters using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC). Pharmacokinetic studies used fluorescence microscopy on sections of pancreas, stomach and duodenum 1 h to 6 days after mTHPC. Highest levels of sensitiser were seen in the gastric and duodenal mucosa and in the acinar pancreas after 2-4 days. For PDT, light at 652 nm was delivered by placing a 0.2 mm diameter bare-ended fibre against the tissue. An energy of 50 J was used 2 or 4 days after 0.1 or 0.3 mg kg-1 mTHPC and animals killed 1 to 7 days later. Maximum necrosis was seen 3 days after PDT with lesions up to 4 mm in pancreas, 4.5 mm in duodenum and 2.5 mm in stomach. By fractionating the light dose, the lesion size could be increased by 30%. The main complication was free or sealed duodenal perforation (avoided by shielding the duodenum). Partial, reversible bile duct obstruction was seen occasionally. There was no macroscopic damage to the bile ducts or major blood vessels. Apart from the duodenum, all lesions healed safely. In this animal model, only the duodenum was at risk of serious, irreversible damage. Treatment is likely to be safer in the much thicker human duodenum. mTHPC is a powerful photosensitiser and suitable for further study for tumours in the region of the pancreas although care is required near the duodenum.
Mlkvy
P
P
National Cancer Centre, Bratislava, Slovakia.
Messmann
H
H
Pauer
M
M
Stewart
J C
JC
Millson
C E
CE
MacRobert
A J
AJ
Bown
S G
SG
D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D008647:Mesocricetus; D008652:Mesoporphyrins / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects; D014018:Tissue Distribution
D008652:Mesoporphyrins; D011838:Radiation-Sensitizing Agents; C072269:temoporfin