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Preparation and Preliminary Evaluation of Technetium-99m-Labeled Fragment E₁ for Thrombus Imaging

Nuclear Medicine Division of the Department of Diagnostic Imaging, Temple University School of Medicine and Hospital, Philadelphia, PA
Johnson-Matthey Pharmaceutical Research, West Chester, PA
McNeil Pharmaceutical (PRI), Spring House, PA

Correspondence: For reprints contact: Linda C. Knight, PhD. Nuclear Medicine, Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19140.

ABSTRACT

Fragment E₁ labeled with ¹²³I has been previously shown to permit imaging of thrombi in patients within as little as 20 min after injection. Because of the relatively rapid localization and blood disappearance of this protein, ^99mTc would be the most clinically acceptable radionuclide for labeling Fragment E₁. In this study, human fragment E₁ was derivatized with a hydrazino nicotinate function to permit radiolabeling with reduced technetium. The modification reaction was carried out while the fragment E₁ was protected in a complex, so that the modification occurred in nonfunctional regions of the fragment E₁ molecule. After radiolabeling with ^99mTc, the modified fragment E₁retained its functional activity, as judged by its binding to fragment DD in vitro. The ability of ^99mTc-fragment E₁ to produce images of venous thrombi was demonstrated in animal models. Images were focally positive within 20 min to 1 hr after injection. Thrombus-to-blood ratios exceeded those from ¹²⁵I-fibrinogen in the same animals. This method of labeling appears to provide an alternative radiolabel to ¹²³I without compromising the function of fragment E₁.

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