Intravenous vs intraperitoneal sensitizer: implications for intraperitoneal photodynamic therapy.
Photodynamic therapy (PDT) is a potential treatment for peritoneal carcinomatosis. However, little data is available regarding the relative distribution of sensitizer to tumor and intra-abdominal organs, optimal route of sensitizer administration, and maximal tolerated light dose. Tumor and normal tissue sensitizer levels were measured by tissue extraction 3, 24, 48 and 72 h after 10 mg/kg of Photofrin II was given intraperitoneally (IP) or intravenously (IV) in a mouse peritoneal tumor model, and the maximal tolerated PDT light dose determined. Equivalent tumor sensitizer levels were obtained regardless of the route of sensitizer administration. Route of administration, however, did affect the kinetics of tumor sensitizer elimination, with the half-time for elimination (T1/2) 113.6 h for IP drug and 60.6 h for IV drug. Route of administration also affected sensitizer levels in several intra-abdominal organs, resulting in somewhat higher tumor to liver and kidney levels at 24 and 72 h after IP sensitizer administration. Despite these tissue distribution differences, route of sensitizer administration did not significantly affect PDT toxicity or mortality when mice were treated with 630 nm light. The maximum tolerated light dose was 1.04 J/cm2. These parameters will prove helpful in designing large scale animal trials assessing the efficacy and safety of intra-abdominal PDT.
Perry
R R
RR
Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Smith
P D
PD
Evans
S
S
Pass
H I
HI
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017323:Dihematoporphyrin Ether; D006415:Hematoporphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; D017323:Dihematoporphyrin Ether