title: Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice.
abstract: The biodistribution of a new and very potent photosensitizer, benzoporphyrin derivative-monoacid, ring A (BPD-MA), was determined in normal and P815 (mastocytoma) or M1 (rhabdomyosarcoma) tumor-bearing DBA/2J mice. A dose of 80 micrograms of 3H-BPD-MA was determined at 3, 24, 48, 72, 96 and 168 h post injection. The following tissues were tested: blood, brain, heart, intestine, kidney, lung, liver, muscle, skin, stomach, spleen, thymus and tumor. The biodistribution of 3H-BPD-MA in normal and tumor-bearing mice was comparable overall. 3H-BPD-MA localized in tumors better than in other tissues except kidney, liver and spleen. The tumor to tissue ratios were in the range 1.5-3 at 24 h post injection and increased further during the next 72 h. The highest levels of 3H-BPD-MA were observed in all tissues at 3 h post injection and decreased rapidly during the first 24 h. After 24 h the clearance from tissues was rather slow. The preliminary clearance data obtained in a group of five normal mice indicated that the majority of the injected dose (60%) cleared from the body via the bile and feces, while only about 4% cleared via kidneys and urine. Studies in which 3H-BPD-MA was extracted from tumor, kidney and liver 3 and 24 h after injection showed that, at 3 h, all the photosensitizing activity in tumor was retained. At 24 h only 39% of the activity was retained and considerably less active material was present in liver and kidney.
authors.affiliation: Quadra Logic Technologies, Vancouver, British Columbia, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Richter
authors.forename: S
authors.initials: S
authors.lastname: Cerruti-Sola
authors.forename: E D
authors.initials: ED
authors.lastname: Sternberg
authors.forename: D
authors.initials: D
authors.lastname: Dolphin
authors.forename: J G
authors.initials: JG
authors.lastname: Levy
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008811:Mice, Inbred DBA; D011166:Porphyrins / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D012016:Reference Values; D012208:Rhabdomyosarcoma / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D014316:Tritium; C504224:benzoporphyrin D