Composition and method

Details Composition and method Composition and method

C - Chemistry, Metallurgy

12

N

C12N 9/64 (2006.01) A61K 51/08 (2006.01) C12N 9/72 (2006.01) C12N 9/99 (2006.01) A61K 49/02 (1990.01)

Patent

CA 2095569

Abstract The present invention provides a radiolabelled t-PA having substantially all plasminogen catalytic sites inactivated and which is able to bind to a thrombus and/or fibrin. It also provides a composition for localising deep venous thrombosis using the compound of this invention, together with a pharmaceutically acceptable carrier, diluent and/or excipient. The invention also provides a process for preparing the compound of this invention, which process comprises reacting t-PA with an agent to inactivate the plasminogen catalytic site followed by cleaving disulfide bridges in the t-PA and labelling the thus-reduced t-PA. The invention specifically provides for the use of recombinant t-PA which is labelled with Tc-99m. Thus the compound of this invention is useful as a radiopharmaceutical for the non-invasive detection of deep vein thrombosis (DVT) in mammals. This radiopharmaceutical has specific thrombus localisation both in vitro and in vivo with an exceptionally fast blood clearance, These properties permit the reliable scintigraphic detection of thrombus in a rabbit model within 60minutes post injection and in humans within 2hr-6hr post injection, In addition, as rt-PA is a product of recombinant DNA technology, it is unlikely to be antigenic and is thus capable of being used more than once in the same mammal.

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