Binding of ¹³¹I-Labeled Tissue-Type Plasminogen Activator on De-Endothelialized Lesions in Rabbits

Tissue-type plasminogen activator (t-PA) which has a high affinity for fibrin in the clot, was labeled with ¹³¹I by the iodogen method, and its binding to de-endothelialized lesions in the rabbit was measured to assess the detectability of thrombi. The de-endothelialized lesion was induced in the abdominal aorta with a Fogarty 4F balloon catheter. Two hours after the de-endothelialization, ¹³¹I-labeled t-PA (125 ± 46 μCi) was injected intravenously. The initial half-life of the agent in blood (n = 12) was 2.9 ± 0.4 min. The degree of binding of ¹³¹I-labeled t-PA to the de-endothelialized lesion was evaluated at 15 min (n = 6) or at 30 min (n = 6) after injection of the agent. In spite of the retention of the biochemical properties of ¹³¹I-labeled t-PA and the presence of fibrin deposition at the de-endothelialized lesion, the binding of t-PA to the lesion was not sufficiently strong. Lesion-to-control ratios (cpm/g/cpm/g) were 1.65 ± 0.40 (at 15 min) and 1.39 ± 1.31 (at 30 min), and lesion-to-blood ratios were 1.39 ± 0.32 (at 15 min) and 1.36 ± 0.23 (at 30 min). These results suggest that radiolabeled t-PA may be inappropriate as a radiopharmaceutical for the scintigraphic detection of a pre-existing thrombotic lesion.

Zusammenfassung

Gewebespezifischer Plasminogen-Aktivator (t-PA), der im Gerinnsel eine hohe Affinität zu Fibrin hat, wurde mit Hilfe der Jodogen-Methode mit ¹³¹J markiert. Bei der Ratte wurde seine Anreicherung in einer Endothelläsion gemessen, um herauszufinden, inwieweit Thromben damit nachweisbar sind. Die Desendothelialisierung dér Bauchaorta in dér Ratte wurde durch einen Fogarty-4F-Ballon-Ka-theter vorgenommen. Zwei Stunden nach der Desendothelialisation wurde ¹³¹J-markiertes t-PA (125 ± 46 (μCi, Mittel ± Standardabweichung) intravenös injiziert. Die initiale Halbwertszeit der Substanz im Blut (n = 12) lag bei 2,9 ± 0,4 min.

Das Ausmaß der Anreicherung des ¹³¹J-markierten t-PA in der Endothelverletzung wurde 15 min (n = 6) oder 30 min (n = 6) nach Gabe dieser Substanz ermittelt. Obwohl die biochemischen Eigenschaften des ¹³¹J-markierten t-PA unverändert blieben und die Fibrinablagerung in der Endothelläsion vorhanden war, war die Bindung des ¹³¹J-markierten t-PA an der Läsion nicht ausreichend, wie im folgenden gezeigt wird. Die Verhältnisse Läsion zu Kontrolle (cpm/g/cpm/ g) waren 1,65 ± 0.40 (nach 15 min) und 1,39 ± 1,31 (nach 30 min), und die Verhältnisse Läsion zu Blut ± 0,32 (nach 15 min) und 1,36 ± 0,23 (nach 30 min). Aufgrund dieser Ergebnisse scheint radioaktiv markiertes t-PA als Radiopharmazeutikum für den szintigraphischen Nachweis einer vorbestehenden thrombotischen Läsion nicht geeignet zu sein.

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