In vivo kinetics of 99mTc labeled recombinant tissue plasminogen activator in rabbits.
Our previous studies demonstrated that 99mTc labeled recombinant tissue plasminogen activator (rt-PA) retained high affinity with fibrin in vitro but showed unexpectedly low uptake in fresh thrombi in vivo. The present study was performed to determine the in vivo kinetics of radiolabeled t-PA in the rabbit. Sequential images and blood samples after the intravenous administration of 99mTc labeled rt-PA in thrombus-bearing rabbits were taken. The radioactivity and immunological level of t-PA and PAI-1 in the solution eluted to each fraction by gel permeation chromatography were measured by means of a well scintillation counter and enzyme-linked immunosorbent assay (ELISA). Most of the radioactivity was eluted in the fraction (Fr. 7) of larger molecular weight than that (Fr. 9) of intact t-PA. The level of intact rt-PA was increased with a regimen involving the preadministration of cold rt-PA which was followed by the administration of hot rt-PA. The level of PAI-1 in plasma showed an increased rebound 15 minutes after the intravenous injection. These results suggest two possible reasons why rt-PA retains high affinity with fibrin in vitro, once radiolabeled, but was ineffective in delineating fresh thrombi with a gamma camera: 1) some plasma components such as PAI-1 combine with circulating radiolabeled rt-PA and form a larger molecule immediately and/or 2) radiolabeled rt-PA is modulated as a consequence of the radiolabeling and forms a larger molecule than intact rt-PA.
Itoh
K
K
Department of Nuclear Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Ieko
M
M
Hiraguchi
E
E
Kitayama
H
H
Tsukamoto
E
E
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008657:Metabolic Clearance Rate; D015609:Organotechnetium Compounds / Q000097:blood / Q000493:pharmacokinetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011817:Rabbits; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics; D013927:Thrombosis / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000493:pharmacokinetics*
D015609:Organotechnetium Compounds; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; C072781:technetium Tc 99m-tissue-type plasminogen activator; D010959:Tissue Plasminogen Activator