Metabolic properties and photosensitizing responsiveness of mono-L-aspartyl chlorin e6 in a mouse tumor model.
A mouse mammary tumor model was used to evaluate metabolic properties of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) and to determine the optimal time interval between drug administration and light treatment for effective photodynamic therapy (PDT). Photosensitizer metabolism was evaluated by comparing tissue distribution patterns of NPe6 having 14C atoms positioned on either the tetrapyrrole ring or on the aspartyl residue. High performance liquid chromatographic analysis of photosensitizer extracted from tumor tissue was also obtained as a function of time after drug administration. NPe6 distribution in tissue samples and pharmacological calculations of area under the curve were similar for both forms of [14]NPe6. Likewise, metabolic contaminants of NPe6 were not detected by high performance liquid chromatographic analysis following extraction of the photosensitizer from tumor tissue. Maximal in vivo PDT effectiveness was achieved when light treatments were started within 2 h of drug injection. PDT effectiveness was decreased by 50% when light treatments were initiated 6 h after drug injection and was abolished with a 12-h interval between NPe6 injection and light exposure. Responsiveness to NPe6-mediated PDT was correlated with photosensitizer levels in the plasma but not in tumor tissue. These results show that NPe6 was not metabolized following in vivo administration and that the responsiveness of NPe6 mediated PDT was associated with vascular clearance of the photosensitizer.
Ferrario
A
A
Clayton Ocular Oncology Center, Childrens Hospital of Los Angeles, California 90027.
Kessel
D
D
Gomer
C J
CJ
D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D011166:Porphyrins / Q000378:metabolism / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C053434:Talaporfin