Compositions for radiolabeling diethylenetriaminepentaacetic acid (DTPA)-dextran
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 99m Tc-pertechnetate, Ascorbic Acid to reduce stannic ions to stannous ions to maintain a reducing environment, α,α-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 99m Tc-pertechnetate, resulting in radiolabeled 99m Tc-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.
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 99m Tc.
17. The composition of claim 16 , comprising greater than about 100 curies of 99m Tc/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.