The aim of this study is to investigate whether 111Indium-labelled recombinant FVIIa (rFVIIa) could be a potential radiopharmaceutical for localization of bleeding sources. DTPA-conjugated rFVIIa was radiolabelled with 111In chloride. In vitro binding efficiency of 111In-DTPA-rFVIIa to F1A2-Mab-sepharose was 99% in buffer, while it was 88–82% in serum. The binding efficiency of 111In-DTPA-rFVIIa to TF (1–209)-sepharose was 48% in buffer whereas 39%–36% in serum, respectively. In vivo experiment was conducted in healthy rats, and gamma camera images were taken immediately after iv. administration of 1.6–1.8 MBq 111In-DTPA-rFVIIa up to 120–130 min. Five min after administration of 111In-DTPA-rFVIIa, percentage of 111In activity was 6.0% in the cardiac region and 24.5% in the liver region. After 2 hours activity was decreased to 3.3% in heart while it had increased to 42.0% in the liver. The 111In-DTPA-rFVIIa might be a potential radiopharmaceutical for visualisation of tissues with significant TF expression such as acute bleeding lesions in the gastrointestinal tract. 1. Introduction The aim of our investigation was to develop a new radiotracer using commercially available recombinant activated coagulation factor VII (rFVIIa, NovoSeven) for localisation of acute bleeding and cancer. rFVIIa is structurally and functionally similar to human plasma-derived coagulation factor VIIa, a glycoprotein of 406 amino acid residues with a molecular weight of 50？kDa [1]. It has been used in treatment of patients with various bleeding disorders like hemophilia A and B patients with inhibitory antibodies and patients with factor VII deficiency and Glanzmann thrombasthenia [2–7]. Blood clotting is initiated via tissue factor (TF), which is normally not exposed to the blood but is constitutively expressed on cells separated from the circulation. Vascular injury exposes TF-rich extravascular tissue, and FVIIa interacts with TF forming the FVIIa/TF complex and initiates the coagulation cascade. Through thrombin generation this leads to formation of a fibrin clot. In addition to its general haemostatic function, TF has also been reported to come in contact with FVIIa in the circulation as a result of structural defects in the vessel wall, angiogenic stimulation, entry to the bloodstream of large numbers of TF-expressing cells, which includes inflammatory leukocytes, leukaemic blast, and cancer cells [8–10]. Interaction between the FVIIa and TF induces the proliferation of certain cancer cells [11, 12]. Therapeutic agent conjugated to FVIIa or FVII resulted in specific
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