COMPARISON OF IODINE-123-DISINTEGRINS FOR IMAGING THROMBI AND EMBOLI IN A CANINE MODEL

Disintegrins are peptides found in viper venoms which bind to platelet s through the glycoprotein IIb-IIIa receptor. The purpose of this work was to evaluate the ability of disintegrins to image thrombi and embo li in vivo. Methods: Eight disintegrins (bitistatin, albolabrin, echis tatin, eristostatin, kistrin, mambin, halysin and barbourin) were puri fied from snake venom, After radiolabeling with I-123, disintegrins we re tested for their ability to image 24-hr-old experimental deep vein thrombi (DVT) and pulmonary emboli in a canine model. Labeled fibrinog en and platelets were used as controls. Gamma camera imaging was perfo rmed during the first 4 hr, after which tissue samples were collected for counting. Results: Of the disintegrins tested, I-123-bitistatin ha d higher uptake in DVT (0.21 +/- .06%ID/g) than any other disintegrin (0.009-0.036%/g, p < 0.05). Bitistatin had higher DVT-to-blood ratios (9.8 +/- 2.5) than all other disintegrins, I-125-fibrinogen or Tc-99m- HMPAO-platelets (p < 0.05), Images of DVT obtained with I-123-bitistat in were focally positive within 1 hr and improved by 4 hr. In pulmonar y emboli, the absolute uptake of I-123-bitistatin (0.64 +/- 0.17%ID/g) was higher than all other compounds (p < 0.05), although barbourin ha d moderate uptake (0.23 +/- 0.11%ID/g) and may also be useful for imag ing pulmonary embolism (PE). The uptake of bitistatin in PE was superi or to both I-125-fibrinogen (0.18 +/- 0.02%ID/g) (p < 0.05) and Tc-99m -HMPAO-platelets (0.14 +/- 0.02%ID/g, p < 0.05). lodine-123-bitistatin had embolus-to-blood ratios averaging 27 +/- 7, which was higher than platelets, fibrinogen, echistatin, mambin or halysin (p < 0.05), Iodi ne-123-bitistatin background in lungs, liver and heart were low, which permitted visualization of all pulmonary emboli by 2-4 hr after injec tion. Conclusion: Labeled bitistatin should be investigated further as an agent which may permit rapid imaging of both thrombi and emboli.