DTPA prodrugs, compositions thereof, and methods of using the same

1. A polymorph of 6,9-bis(carboxymethyl)-3-(2-ethoxy-2-oxoethyl)-11-oxo-12-oxa-3,6,9-triazatetradecan-1-oic acid characterized by a powder x-ray diffraction pattern substantially the same as that shown in FIG. 6D and/or a powder x-ray diffraction pattern having peaks at about 8.1, 12.0, 13.8, 15.4, 16.0, 16.6, 18.3, 19.3, 21.4, 22.1, 24.0, 26.5, and 29.2±0.2 degrees 2 theta,

wherein the polymorph has a melting point in a range from 133° C. to 141° C.

2. The polymorph of claim 1 , wherein the melting point is measured using differential scanning calorimetry over a range of about 25° C. to about 320° C. with a heating rate of about 10.00° C./min.

3. A process of preparing the polymorph of 6,9-bis(carboxymethyl)-3-(2-ethoxy-2-oxoethyl)-11-oxo-12-oxa-3,6,9-triazatetradecan-1-oic acid of claim 1 , comprising

(a) combining DTPA bis-anhydride and absolute ethanol to form a reaction mixture;

(b) heating the reaction mixture to reflux while stirring for about 1.5 hours;

(c) filtering the reaction mixture to form a filtrate;

(d) cooling the filtrate to a temperature below about 20° C. to form a precipitate of a polymorph of 6,9-bis(carboxymethyl)-3-(2-ethoxy-2-oxoethyl)-11-oxo-12-oxa-3,6,9-triazatetradecan-1-oic acid;

(e) filtering the filtrate to obtain the precipitate;

(f) optionally washing the precipitate with cold ethanol;

(g) optionally washing the precipitate with methyl tert-butyl ether to form a filter cake;

(h) optionally mixing the filter cake with ethanol to form a second slurry;

(i) optionally heating the second slurry to a temperature of about 70° C.;

(j) optionally filtering the second slurry to form a second filtrate;

(k) optionally cooling the second filtrate to a temperature below about 20° C. to form a second precipitate;

(l) optionally filtering the second filtrate to obtain the second precipitate; and

(m) optionally drying the precipitate, thereby obtaining the polymorph.

4. A method of treating a subject to remove a radioactive element from the subject comprising:

administering a therapeutically effective amount of the polymorph of claim 1 to a subject, thereby removing the radioactive element from the subject.

5. The method of claim 4 , wherein the administering step delivers to the subject from about 1 mg to about 2,000 mg of the polymorph per kilogram of the subject's total body weight.

6. The method of claim 4 , wherein the administering step is prior to the subject's exposure to a radioactive element.

7. The method of claim 6 , wherein the administering step is carried out to prevent incorporation of a radioactive element into the subject's tissues, organs, bones, or any combination thereof.

8. The method of claim 4 , wherein the administering step is after the subject's exposure to a radioactive element.

9. The method of claim 4 , wherein the radioactive element comprises an isotope of plutonium (Pu), americium (Am), curium (Cm), or any combination thereof.

10. The method of claim 4 , wherein the subject is a mammal.