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):	Nunn; Adrian D. (Hopewell, NJ), Feld; Thomas A. (Califon, NJ), Treher; Elizabeth N. (Washington Crossing, PA)
Assignee:	E. R. Squibb & Sons, Inc. (Princeton, NJ)
Application Number:	06/723,601
Patent Claims:	1. A boronic acid adduct of technetium-99m dioxime complexes having the formula wherein X is an anion; Y is a vicinal dioxime having the formula ##STR6## or a pharmaceutically acceptable salt thereof, wherein R.sub.1 and R.sub.2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R.sub.1 and R.sub.2 are --(CR.sub.8 R.sub.9).sub.n --wherein n is 3, 4, 5 or 6 and R.sub.8 and R.sub.9 are each independently hydrogen or alkyl; and Z is a boron derivative of the formula wherein R.sub.3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R.sub.4 R.sub.5 N)-alkyl and R.sub.4 and R.sub.5 are each independently hydrogen, alkyl, or arylalkyl, or R.sub.4 and R.sub.5 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, .alpha.-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 .alpha.-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).sub.3 methyl boron. 15. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime).sub.3 1-methylpropyl boron. 16. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime).sub.3 4-methylphenyl boron. 17. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime).sub.3 cyclopentyl boron. 18. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine) 1,2-cyclohexanedione dioxime).sub.3 ethyl boron. 19. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime).sub.3 4-(t-butyl)phenyl boron. 20. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine) (dimethyl glyoxime).sub.3 2-methyl-1-propyl boron. 21. The boronic acid adduct in accordance with claim 1, 99mTc (chlorine) (1,2-cyclohexanedione dioxime).sub.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 R.sub.3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxy-alkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl, or R.sub.4 R.sub.5 N-alkyl and R.sub.4 and R.sub.5 are each independently hydrogen, alkyl, or arylalkyl, or R.sub.4 and R.sub.5 when taken together with nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle, and R.sub.7 is hydrogen, alkyl or aryl; (iii) a dioxime having the formula ##STR8## or a pharmaceutically acceptable salt thereof, wherein R.sub.1 and R.sub.2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R.sub.1 and R.sub.2 are --(CR.sub.8 R.sub.9).sub.n --wherein n is 3, 4, 5 or 6 and R.sub.8 and R.sub.9 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 .alpha.-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.