Sensitizer for photodynamic therapy of cancer: a comparison of the tissue distribution of Photofrin II and aluminum phthalocyanine tetrasulfonate in nude mice bearing a human malignant tumor.
The distribution of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in tissues of BALB/c nu/nu nude mice bearing the LOX human melanoma was measured fluorimetrically at different times after intraperitoneal injection of the drugs, 20 mg/kg body weight. The plasma levels of the drugs as well as the excretion in feces and urine were also determined. The plasma concentrations of both drugs were found to build up in a similar manner during the first 30 min after injection. Thereafter, the plasma level of AIPCS4 decreased exponentially with an elimination half-life of 1.5 hr. The kinetics of elimination of P-II from the plasma were consistent with a 2-compartment model, with 90% of sensitizer lost with a half-life of about 5 hr, and the remaining fraction with a half-life of 30 hr. About 80% of the injected dose of P-II was excreted in the feces during the 7-days following injection, while 77% of AIPCS4 was excreted in the urine during the same period. After injection of a dose of 20 mg/kg, the concentrations of P-II in the LOX tumor as well as in the skin, muscle, brain, heart, lung, kidney and liver increased for about 24 hr, then remained constant or decreased slowly for the next 48 hr, after which they decreased slightly faster. On the other hand, the concentrations of APICS4 in most tissues as well as in the tumor peaked at about 30 min, then decreased with a half-life of between 1.5 and 3 hr. The tumor/skin concentration ratio was about 1 for both drugs (1-24 hr after injection). The tumor/muscle concentration ratio was about 2 for P-II at all sampling times, and maximally 10 (at 18 hr after injection) for AIPCS4. In the present tumor model, the tumor/tissue concentration ratio for all tissues at 1 hr and at 24 hr after the injection was equal for the 2 drugs or higher for AIPCS4.
Peng
Q
Q
Department of Biophysics, Institute for Cancer Research, Montebello, Oslo, Norway.
Moan
J
J
Kongshaug
M
M
Evensen
J F
JF
Anholt
H
H
Rimington
C
C
D000818:Animals; D017323:Dihematoporphyrin Ether; D005260:Female; D006414:Hematoporphyrin Photoradiation; D006415:Hematoporphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053685:Laser Therapy; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D014018:Tissue Distribution
D006415:Hematoporphyrins; D007211:Indoles; D009942:Organometallic Compounds; C060570:aluminum phthalocyanine; D017323:Dihematoporphyrin Ether