Neorx Corporation

Stephen W Hadley

Daniel S Wilbur

John M Reno

Marjorie A Mohler

A bicyclic, non-aromatic hydrocarbon compound, optionally having one or more N, O or S atoms in the bicyclic skeleton, and having as substituents an acid group and an amido group, which are vicinal and in a syn-position, wherein the amido group is not anilido and the acid group is carboxyl or carboxyl in a form metabolizable to a free carboxyl group, and wherein said bicyclic skeleton is optionally unsaturated, except in the bond between said groups, acid-cleavably links an amide-containing active agent to a targeting agent, which is linked by a linker arm to the bicyclic skeleton.

Acid-cleavable compound

A fibrin-binding protein such as t-PA is labeled with a detectable substance, such as a radionuclide, and administered to a patient for diagnosis of blood clots and for monitoring the dissolution thereof during therapy. The detectable substance preferably is attached to t-PA through linkers which specifically bind to the portion of the t-PA protein responsible for enzymatic activity, thereby diminishing this activity while leaving the fibrin-binding property of the protein intact.

Method of diagnosing blood clots using fibrin-binding proteins

Vinyl radiohalogenated small molecules as shown in formulas I and II: ##STR1## wherein *X is radiohalogen, C.dbd.C is a double bonded set of sp.sup.2 hybridized carbon atoms, and substituents R.sub.1, and R.sub.2 are as defined in the specification. Y is a substituent containing any of the groups described for R.sub.1 and R.sub.2, except that Y cannot be hydrogen, and bearing a functional group suitable for binding to protein under conditions that preserve the biological activity of the protein. The compounds of formulas I and II can be coupled to proteins such as monoclonal antibodies to provide reagents for diagnostic and therapeutic applications. Also metalated precursors of compounds I and II, as well as radiopharmaceutical reagent kits containing any of the subject small molecules.

Vinyl substituted radiohalogen conjugates for protein labeling

A process for recovering At-211 from a target and simultaneously producing an At-211-labeled radiopharmaceutical agent involves introducing volatilized At-211, produced by dry distillation of an irradiated Bi-209 target, into a solution containing a compound that binds the At-211 to form an At-211-labeled radiopharmaceutical agent. The radiopharmaceutical agent may have therapeutic use as is, or may be attached to a targeting protein such as an antibody prior to administation to a patient.

Process for isolation and radiolabeling of pharmaceuticals with isotopes

Vinyl radiohalogenated small molecules as shown in formulas I and II: ##STR1## wherein *X is a radiohalogen, C.dbd.C is a double bonded set of sp.sup.2 hybridized carbon atoms, and substituents R.sub.1, R.sub.2, and Y are as defined below. R.sub.1 and R.sub.2 are substituents independently selected from among hydrogen; alkyl or substituted alkyl, provided that any sp.sup.2 or sp carbon atom substituted on the alkyl is separated from C.dbd.C by at least one fully substituted sp.sup.3 carbon atom; aryl or substituted aryl, provided that the aryl is bonded directly to C.dbd.C; heteroalkyl, provided, first, that no heteroatom of the heteroalkyl bonds directly to C.dbd.C and, second, that any sp.sup.2 or sp hybridized carbon bonded to a heteroatom of the heteroalkyl is not bonded directly to or otherwise conjugated with C.dbd.C and, third, that where a single sp.sup.3 carbon intervenes between C.dbd.C and an sp.sup.2 or sp carbon bonded to a heteroatom that intervening sp.sup.3 carbon must be fully substituted; heteroaryl, provided that a heteroatom of the heteroaryl is not bonded directly with C 50 C; mixed alkylaryl, provided first, that no heteroatom is bonded to C.dbd.C and, second that either an aryl moiety of the mixed alkylaryl is directly bonded to C.dbd.C or that any aryl moiety is separated from C.dbd.C by at least one sp.sup.3 carbon atom and, where only one sp.sup.3 hybridized carbon atom intervenes between C.dbd.C and an aryl moiety, that intervening sp.sup.3 carbon must be fully substituted. Y is substituent containing any of the groups described above for R.sub.1 and R.sub.2, except that Y cannot be hydrogen, and bearing a functional group suitable for binding to protein under conditions that preserve the biological activity of the protein. The compounds of formulas I and II can be coupled to proteins such as monoclonal antibodies ot provide reagents for diagnostic and therapeutic applications. Also metalated precursors of compounds I and II, as well as radiophormaceutical reagent kits containing any of the subject small molecules.

Growing community of inventors

Seattle, WA, United States of America

Stephen W Hadley