Annals of Nuclear Medicine

, Volume 8, Issue 3, pp 193–199 | Cite as

In vivo kinetics of99mTc labeled recombinant tissue plasminogen activator in rabbits

  • Kazuo Itoh
  • Masahiro Ieko
  • Etsuro Hiraguchi
  • Hide Kitayama
  • Eriko Tsukamoto
Original Article


Our previous studies demonstrated that99mTc labeled recombinant tissue plasminogen activator (rt-PA) retained high affinity with fibrinin vitro but showed unexpectedly low uptake in fresh thrombiin vivo. The present study was performed to determine thein vivo kinetics of radiolabeled t-PA in the rabbit.

Sequential images and blood samples after the intravenous administration of99mTc 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 fibrinin 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.

Key words

recombinant tissue plasminogen activator radiolabeling pharmacokinetics animal study 


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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Kazuo Itoh
    • 1
  • Masahiro Ieko
    • 2
  • Etsuro Hiraguchi
    • 3
  • Hide Kitayama
    • 2
  • Eriko Tsukamoto
    • 1
  1. 1.Department of Nuclear MedicineHokkaido University School of MedicineSapporoJapan
  2. 2.Department of Second Internal MedicineHokkaido University School of MedicineJapan
  3. 3.Department of Second SurgeryHokkaido University School of MedicineJapan

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