Comparison of iodine-123-disintegrins for imaging thrombi and emboli in a canine model.
Disintegrins are peptides found in viper venoms which bind to platelets through the glycoprotein IIb-IIIa receptor. The purpose of this work was to evaluate the ability of disintegrins to image thrombi and emboli in vivo.


METHODS
Eight disintegrins (bitistatin, albolabrin, echistatin, eristostatin, kistrin, mambin, halysin and barbourin) were purified from snake venom. After radiolabeling with 123I, disintegrins were tested for their ability to image 24-hr-old experimental deep vein thrombi (DVT) and pulmonary emboli in a canine model. Labeled fibrinogen and platelets were used as controls. Gamma camera imaging was performed during the first 4 hr, after which tissue samples were collected for counting.


RESULTS
Of the disintegrins tested, 123I-bitistatin had 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, 125I-fibrinogen or 99mTc-HMPAO-platelets (p < 0.05). Images of DVT obtained with 123I-bitistatin were focally positive within 1 hr and improved by 4 hr. In pulmonary emboli, the absolute uptake of 123I-bitistatin (0.64 +/- 0.17% ID/g) was higher than all other compounds (p < 0.05), although barbourin had moderate uptake (0.23 +/- 0.11% ID/g) and may also be useful for imaging pulmonary embolism (PE). The uptake of bitistatin in PE was superior to both 125I-fibrinogen (0.18 +/- 0.02% ID/g) (p < 0.05) and 99mTc-HMPAO-platelets (0.14 +/- 0.02% ID/g, p < 0.05). Iodine-123-bitistatin had embolus-to-blood ratios averaging 27 +/- 7, which was higher than platelets, fibrinogen, echistatin, mambin or halysin (p < 0.05). Iodine-123-bitistatin background in lungs, liver and heart were low, which permitted visualization of all pulmonary emboli by 2-4 hr after injection.


CONCLUSIONS
Labeled bitistatin should be investigated further as an agent which may permit rapid imaging of both thrombi and emboli.
Knight
L C
LC
Department of Diagnostic Imaging, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Maurer
A H
AH
Romano
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D019483:Disintegrins / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D004285:Dogs; D005069:Evaluation Studies as Topic; D005340:Fibrinogen; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008969:Molecular Sequence Data; D015609:Organotechnetium Compounds; D010091:Oximes; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D012910:Snake Venoms; D019690:Technetium Tc 99m Exametazime; D013924:Thrombophlebitis / Q000000981:diagnostic imaging*; D013997:Time Factors; D014018:Tissue Distribution; D014688:Venoms
D019483:Disintegrins; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D010091:Oximes; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012910:Snake Venoms; D014688:Venoms; C062186:bitistatin; D019690:Technetium Tc 99m Exametazime; D005340:Fibrinogen