Distribution and excretion of radiolabeled temoporfin in a murine tumor model.
The biodistribution and excretion of temoporfin (tetra[m-hydroxyphenyl]chlorin, m-THPC), a recently developed photosensitizer, was investigated in BALB/c mice. [14C]temoporfin was administered intravenously (0.73 mumol/kg) to tumor-free mice or to mice implanted with the Colo 26 colorectal carcinoma. Blood, tissue and fecal samples were collected for 35 days and 10 days postdose from tumor-free mice and tumor-bearing mice, respectively. Blood concentrations fell rapidly such that at later time points they were indistinguishable from background counts. Tumor concentrations rose to a peak of 0.34 microgram temoporfin equivalents/mL at 2 days and then declined in parallel (log plot) with the blood concentrations. Tumor: tissue ratios at 2 days for skin, adipose tissue and skeletal muscle underlying the tumor were 1.5, 2.3 and 3.8, respectively. By 4 days the corresponding values were 1.6, 3.4 and 4.0. Nearly 40% of the administered radioactivity was excreted in the feces in the first 24 h and more than 80% had been excreted by 20 days. Less than 0.2% of the dose was recovered from the urine. An elimination half-life of 10-12 days was calculated from the excretion data.
Whelpton
R
R
Department of Pharmacology, Queen Mary and Westfield College, University of London, UK. R. Whelpton@QMW.AC.UK
Michael-Titus
A T
AT
Jamdar
R P
RP
Abdillahi
K
K
Grahn
M F
MF
D000818:Animals; D002250:Carbon Radioisotopes; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006207:Half-Life; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin