A new approach to cancer therapy due to appropriate uptake and retention kinetics of meta-tetrahydroxy-phenylchlorin in a human fibroblast cell line.
Studies have shown that meta-tetrahydroxy-phenylchlorin is an efficient tumor targeting agent for laser photodynamic therapy. The effectiveness of this approach for cancer treatment depends on drug concentration, incubation time and extracellular protein. We studied uptake and retention kinetics of mTHPC in a human fibroblast cell line. Our results clearly demonstrate a difference in the amount of extracellular mTHPC at an incubation temperature of 37 degrees C compared to 20 degrees C and 4 degrees C. pH-values were always constant and not responsible for the increase. Furthermore, both absorption and fluorescence of mTHPC increase when incubated at normal human body temperature. Incubation of human fibroblast cells with mTHPC (10 micg/mL) showed that intracellular mTHPC increases in a linear manner reaching saturation after 24 hours and declining until 48 hours with concommitant increase of supernatant mTHPC. Therefore, we believe that tumor cells can be treated optimally with PDT following a delay > 24 hours after drug administration with a minimum of damage to surrounding normal tissues.
Wierrani
F
F
Department of Gynecology and Obstetrics, Rudolfstiftung Hospital, Vienna, Austria.
Fiedler
D
D
Schnitzhofer
G
G
Stewart
J C
JC
Gharehbaghi
K
K
Henry
M
M
Grin
W
W
Grünberger
W
W
Krammer
B
B
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002460:Cell Line; D004355:Drug Stability; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008750:Methyldopa / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D010778:Photochemotherapy / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012996:Solutions; D013050:Spectrometry, Fluorescence; D013696:Temperature
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D012996:Solutions; D008750:Methyldopa; C028341:2-methyl-3-(2,4,5-trihydroxyphenyl)alanine