The significance of the nature of the photosensitizer for photodynamic therapy: quantitative and biological studies in the colon.
Photodynamic therapy (PDT) depends on the interaction of light with an administered photosensitiser to produce a local cytotoxic effect. The most widely used photosensitiser is haematoporphyrin derivative (HpD), but newer photosensitisers such as aluminium sulphonated phthalocyanine (A1SPc) are promising. HpD and A1SPc have been compared as photosensitisers for colonic PDT in the rat. Quantitative analysis showed that following injection of a standard photosensitiser dose, A1SPc produced more damage than HpD with increasing energy (fluence). Alteration of the injected dose of photosensitiser did not produce a clear difference. There was a loss of reciprocity for photosensitiser/light combinations at low injected dose (0.5 mg kg-1), both HpD and A1SPc producing no damage. Similarly at high photosensitiser dosage (25 mg kg-1) there was no quantitative difference between A1SPc and HpD. Photosensitiser photodegradation at low photosensitiser doses, and light attenuation by high tissue concentrations of A1SPc account for these findings. PDT with either agent produced the same histological damage and full thickness necrosis produced no mechanical weakening of the colon measured by the bursting pressure. The submucosal collagen was preserved and healing was by regeneration.
Barr
H
H
Department of Surgery, Rayne Institute, University College London, UK.
MacRobert
A J
AJ
Tralau
C J
CJ
Boulos
P B
PB
Bown
S G
SG
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000633:toxicity*; D007211:Indoles / Q000633:toxicity*; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
D006415:Hematoporphyrins; D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C048577:aluminum tetrasulfophthalocyanine; D017324:Hematoporphyrin Derivative