Platelet binding and biodistribution of [99m Tc]rBitistatin in animal species and humans

Abstract Introduction99m Tc recombinant bitistatin (rBitistatin) is a radioligand for αIIb β3 (glycoproteins IIb/IIIa) receptor on platelets and is being developed as a diagnostic radiopharmaceutical for in vivo imaging of acute thrombi and emboli. Prior to the first administration of [99m Tc]rBitis...

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Bibliographic Details
Published in:Nuclear medicine and biology 2007-10, Vol.34 (7), p.855-863
Main Authors: Knight, Linda C, Romano, Jan E, Bright, Lewis T, Agelan, Alexis, Kantor, Steven, Maurer, Alan H
Format: Article
Language:English
Subjects:
[ 99mTc]rBitistatin
Animals
Blood Platelets - diagnostic imaging
Blood Platelets - metabolism
Dogs
GPIIb/IIIa receptor
Guinea Pigs
Humans
Metabolic Clearance Rate
Mice
Peptides - pharmacokinetics
Platelets
Radiology
Radionuclide Imaging
Radiopharmaceuticals - pharmacokinetics
Species Specificity
Technetium - pharmacokinetics
Thrombus imaging
Tissue Distribution
α IIbβ 3 integrin
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Summary:Abstract Introduction99m Tc recombinant bitistatin (rBitistatin) is a radioligand for αIIb β3 (glycoproteins IIb/IIIa) receptor on platelets and is being developed as a diagnostic radiopharmaceutical for in vivo imaging of acute thrombi and emboli. Prior to the first administration of [99m Tc]rBitistatin to human subjects, its biodistribution and effects on platelets were evaluated in animals. This paper reports findings in animal studies in comparison with initial findings in normal human subjects. Methods [99m Tc]rBitistatin was administered to mice, guinea pigs and dogs to assess time-dependent organ distribution, urinary excretion and blood disappearance rates. Blood samples were analyzed to determine radioligand binding to circulating platelets and the extent of plasma protein binding. The effect of [99m Tc]rBitistatin on circulating platelet count was determined. These factors were also determined in normal human subjects who received [99m Tc]rBitistatin as part of a Phase I clinical trial. Results The main organs that accumulated [99m Tc]rBitistatin were kidneys, liver and spleen in all animal species and humans. The main organs seen on human images were the kidneys and spleen. Liver uptake was fainter, and soft-tissue background was low. [99m Tc]rBitistatin bound to circulating platelets in blood, with a higher percentage of binding to platelets in guinea pigs and dogs compared to that in humans. Plasma protein binding was low and of little consequence in view of platelet binding. The main route of excretion was through the urine. [99m Tc]rBitistatin did not affect platelet counts in humans or dogs. Conclusions [99m Tc]rBitistatin, when administered at low doses for imaging, has no adverse effects on platelets and has the qualitative biodistribution predicted by animal studies. [99m Tc]rBitistatin was found to bind to circulating platelets in humans, suggesting that it will be able to bind to activated platelets in vivo in patients with acute thrombi.
ISSN:0969-8051
1872-9614
DOI:10.1016/j.nucmedbio.2007.03.014