Claims for Patent: 9,439,985

Summary for Patent: 9,439,985

Title:	Compositions for radiolabeling diethylenetriaminepentaacetic acid (DTPA)-dextran
Abstract:	The subject invention relates to the compositions for radiolabeling Diethylenetriaminepentaacetic Acid (DTPA)-dextran with Technetium-99m and for stabilizing the DTPA-dextran Cold Kit. The composition contains Stannous Chloride ions to reduce .sup.99mTc-pertechnetate, Ascorbic Acid to reduce stannic ions to stannous ions to maintain a reducing environment, .alpha.,.alpha.-Trehalose to add bulk and to stabilize the lyophilized composition without interfering with the radiochemical yield, and Glycine to transchelate Technetium-99m under highly acidic conditions to facilitate radiolabeling DTPA-dextran with high radiochemical purity. In addition, the invention pertains to methods for making and using the compositions. The reconstitution of the lyophilized composition by .sup.99mTc-pertechnetate, resulting in radiolabeled .sup.99mTc-DTPA-dextran in a composition between pH 3 to 4. This invention contains a Diluent vial, which when used will shift the pH to a moderately acidic pH, which would provide less pain on injection and ease-of-use to clinical practioners for adjusting its potency.
Inventor(s):	Magneson; Gerald Ross (Powell, OH), Orahood; Richard Cushman (Delaware, OH)
Assignee:	Navidea Biopharmaceuticals, Inc. (Dublin, OH)
Application Number:	14/039,648
Patent Claims:	1. A composition comprising: (a) a DTPA-dextran present in a concentration up to 0.5 mg/mL; (b) a sugar selected from the group consisting of non-reducing disaccharides, wherein the sugar is present in a concentration up to 2% (w/v); (c) a non-sulfhydryl anti-oxidant (d) a stannous salt dihydrate present in a concentration up to 75 micrograms/mL; and (e) a transchelator present in a concentration up to about 0.5 mg/mL. 2. The composition of claim 1, wherein the DTPA-dextran contains multiple DTPA groups conjugated to dextran in the molar range of about 2:1 to 12:1. 3. The composition of claim 1, wherein the DTPA-dextran contains dextran in the average molecular weight range of about 5,000 to 20,000 Daltons. 4. The composition of claim 1, wherein the DTPA-dextran is DTPA-mannosyl-dextran containing a molar ratio range of about 2:1 to 12:1 conjugated mannose groups to DTPA-dextran. 5. The composition of claim 1, wherein the non-reducing disaccharide is trehalose dihydrate. 6. The composition of claim 1, wherein the non-sulfhydryl anti-oxidant is ascorbic acid or a salt thereof. 7. The composition of claim 1, wherein said transchelator is glycine. 8. The composition of claim 1, wherein a salt of the transchelator is sufficient to buffer said composition within a pH range of about 3 to about 4. 9. The composition of claim 1, wherein a salt of the transchelator is sufficient to buffer said composition within a pH range of 3.2+/-0.2. 10. The composition of claim 1, further comprising a diluent. 11. The composition of claim 10, wherein the diluent comprises sterile water. 12. The composition of claim 11, wherein the diluent raises a pH to greater than about pH 5. 13. The composition of claim 11, wherein the diluent raises a pH from a range of about 3 to about 4 to a pH range of greater than about 5. 14. The composition of claim 10, wherein the diluent comprises components selected from a group consisting of: sodium phosphate, potassium phosphate, sodium chloride, phenol, and combinations thereof. 15. The composition of claim 10, wherein the diluent comprises sodium phosphate, potassium phosphate, sodium chloride, and phenol. 16. The composition of claim 1, further comprising .sup.99mTc. 17. The composition of claim 16, comprising greater than about 100 curies of .sup.99mTc/mmol of the DTPA-dextran. 18. The composition of claim 1, further comprising nitrogen gas. 19. The composition of claim 1, wherein the transchelator is glycine and the non-sulfhydryl anti-oxidant is sodium ascorbate. 20. The composition of claim 1, wherein the non-sulfhydryl anti-oxidant is present in a concentration of about 0.5 mg/mL. 21. A composition comprising: DTPA-dextran present in a concentration up to 0.5 mg/mL; trehalose dihydrate present in a concentration up to 2% (w/v); sodium ascorbate; stannous dichloride dihydrate present in a concentration up to 75 micrograms/mL; and glycine present in a concentration up to about 0.5 mg/mL. 22. The composition of claim 21, wherein the sodium ascorbate is present in a concentration of about 0.5 mg/mL.