Claims for Patent: 4,705,849

Summary for Patent: 4,705,849

Title:	Boronic acid adducts of technetium-99m dioxime complexes
Abstract:	Boronic acid adducts of technetium-99m dioxime complexes are useful for imaging the myocardium, hepatobiliary system, brain and blood pool in humans and other mammalian species.
Inventor(s):	Adrian D. Nunn, Thomas A. Feld, Elizabeth N. Treher
Assignee:	Bracco International BV
Application Number:	US06/723,601
Patent Claims:	1. A boronic acid adduct of technetium-99m dioxime complexes having the formula 99mTc X(Y).sub.3 Z, wherein X is an anion; Y is a vicinal dioxime having the formula ##STR6## or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are --(CR8 R9)n --wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; and Z is a boron derivative of the formula B--R.sub.3 wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4 R5 N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle. 2. A boronic acid adduct in accordance with claim 1, wherein X is a halide. 3. A boronic acid adduct in accordance with claim 1, wherein X is chloride or bromide. 4. A boronic acid adduct in accordance with claim 1, wherein X is chloride. 5. A boronic acid adduct in accordance with claim 1, wherein Y is dimethyl glyoxime, 1,2-cyclohexanedione dioxime, 1,2-ethanedione dioxime, α-furyldioxime, 1,2-cyclopentanedione dioxime, or 3-methyl-1,2-cyclopentanedione dioxime. 6. A boronic acid adduct in accordance with claim 1, wherein Y is dimethyl glyoxime 7. A boronic acid adduct in accordance with claim 1, wherein Y is 1,2-cyclohexanedione dioxime. 8. A boronic acid adduct in accordance with claim 1, wherein Y is 1,2-ethanedione dioxime. 9. A boronic acid adduct in accordance with claim 1, wherein Y is α-furyldioxime. 10. A boronic acid adduct in accordance with claim 1, wherein the boron derivative Z is B-alkyl. 11. A boronic acid adduct in accordance with claim 1, wherein the boron derivative Z is B-alkoxy. 12. A boronic acid adduct in accordance with claim 1, wherein the boron derivative Z is B-benzyl. 13. A boronic acid adduct in accordance with claim 1, wherein the boron derivative Z is B-cycloalkyl. 14. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine) (1,2-cyclohexanedione dioxime)3 methyl boron. 15. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime)3 1-methylpropyl boron. 16. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime)3 4-methylphenyl boron. 17. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime)3 cyclopentyl boron. 18. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine) 1,2-cyclohexanedione dioxime)3 ethyl boron. 19. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime)3 4-(t-butyl)phenyl boron. 20. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine) (dimethyl glyoxime)3 2-methyl-1-propyl boron. 21. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine) (1,2-cyclohexanedione dioxime)3 hydroxy boron. 22. A kit suitable for labeling with technetium-99m, said kit comprising:(i) a source of anion; (ii) a boronic acid derivative, or compounds which can react in situ to form a boronic acid derivative, having the formula ##STR7## or a pharmaceutically acceptable salt thereof, wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxy-alkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl, or R4 R5 N-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle, and R7 is hydrogen, alkyl or aryl; (iii) a dioxime having the formula ##STR8## or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are --(CR8 R9)n --wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; and (iv) a reducing agent. 23. A kit in accordance with claim 22, wherein the source of anion is a source of halide. 24. A kit in accordance with claim 22, wherein the source of anion is a source of chloride or bromide. 25. A kit in accordance with claim 22 wherein the dioxime is dimethyl glyoxime, 1,2-cyclohexanedione dioxime, 1,2-ethanedione dioxime or α-furyldioxime. 26. A kit in accordance with claim 22, wherein the dioxime is dimethyl glyoxime. 27. A kit in accordance with claim 22, wherein the dioxime is 1,2-cyclohexanedione dioxime. 28. A kit in accordance with claim 22, wherein the reducing agent is a stannous salt.