Platelet-derived endothelial cell growth factor. Pharmacokinetics, organ distribution and degradation after intravenous administration in rats.
Platelet-derived endothelial cell growth factor (PD-ECGF) stimulates chemotaxis of endothelial cells in vitro and has angiogenic activity in vivo. Recently PD-ECGF was shown to have thymidine phosphorylase activity. In order to study possible therapeutic applications of PD-ECGF we used a rat model to determine its pharmacokinetics and tissue distribution after intravenous injection. [125I]PD-ECGF disappeared from the plasma in a biphasic manner, with estimated distribution and elimination half-lives of 17 min and 7 h, respectively. PD-ECGF was metabolized in the liver, excreted via the bile, and not accumulated in any organ system. The stability and long half-life in the circulation, together with the specificity for endothelial cells, suggest that PD-ECGF may be useful as a therapeutic agent to stimulate re-endothelialization in vivo, or, in view of its thymidine phosphorylase activity, in chemotherapy, by decreasing the pool of available thymidine.
Waltenberger
J
J
Ludwig Institute for Cancer Research, Uppsala Branch, Sweden.
Usuki
K
K
Fellström
B
B
Funa
K
K
Heldin
C H
CH
D000818:Animals; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D013939:Thymidine Phosphorylase / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D013939:Thymidine Phosphorylase