99mTc-Acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-3-iodo-Tyr-Thr-Leu-Leu-Lys-Gly-NC100194

Excerpt

Thrombosis plays a major role in many cardiovascular diseases such as myocardial infarction, pulmonary embolism, deep venous thrombosis, or cerebral venous thrombosis (1). Thrombosis occurs by an activation process of thrombin, which then converts fibrinogen into fibrin. Thrombin initiates the cross-linking of the polymerized fibrin via the activation of a transglutamase enzyme called coagulation factor XIII (FXIIIa indicates activated factor XIII) (2). FXIIIa increases acute thrombus stability by rapidly cross-linking a lysine residue in fibrin α- and γ-chains to a glutamine residue in α-2 antiplasmin. FXIIIa has an in vivo catalytic half-life (t_½) of ~20 min (3).

NC100668 (Acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-3-iodo-Tyr-Thr-Leu-Leu-Lys-Gly-NC100194) is a probe that is recognized by the enzyme FXIIIa and covalently binds to fibrin by means of the transglutamase activity of FXIIIa (4, 5). NC100194 (N,N-bis(N-(1,1-dimethyl-2-(hydroxylimino-)propyl)aminoethyl)aminoethylamine) is a ^99mTc-chelator. Single-photon emission computed tomography (SPECT) imaging with an FXIIIa probe may be a useful tool in the diagnosis of thrombosis and may provide valuable information currently unavailable through anatomically-based imaging modalities.

Preliminary research has shown that ^99mTc-NC100668 is capable of measuring the activity of FXIIIa and visualizing thrombus in vivo (6, 7). ^99mTc-NC100668 may be used as a molecular diagnostic tool for therapy with fibrinolytic or anti-FXIIIa inhibitors, and other drugs for diseases such as cerebral venous thrombosis, ischemic stroke, or myocardial infarction. Additional and more extensive research studies are needed to fully assess the potential application of the ^99mTc-NC100668 imaging modality.