PREPARATIONS OF META-IODOBENZYLGUANIDINE AND PRECURSORS THEREOF

1 . A preparation comprising a polymer, the polymer comprising a monomer of formula (I):

or a pharmaceutically acceptable salt thereof, wherein leachable tin is present in the preparation at a level within a range of about 0 ppm to about 150 ppm.

2 . The preparation of claim 1 , wherein the pharmaceutically acceptable salt is the HOAc salt.

3 . The preparation of claim 1 , which preparation is enclosed in a container under inert gas.

4 . The preparation of claim 3 , wherein the inert gas is nitrogen.

5 . The preparation of claim 1 , wherein the level of leachable tin is within a range of about 0 ppm to about 120 ppm.

6 . The preparation of claim 1 , wherein the level of leachable tin is within a range of about 0 ppm to about 50 ppm.

7 . The preparation of claim 1 , wherein the polymer comprising monomer of formula (I), or the pharmaceutically acceptable salt thereof, makes up at least 98% of the preparation.

8 . The preparation of claim 1 , the preparation comprising less than 1.5 wt % water relative to the wt % of the preparation.

9 . The preparation of claim 1 , the preparation comprising less than 1.0 wt % water relative to the wt % of the preparation.

10 . The preparation of claim 1 , the preparation comprising less than 0.5 wt % organic solvent relative to the wt % of the preparation.

11 . The preparation of claim 1 , the polymer comprising less than about 0.5 wt % of a monomer of formula (IV):

or a pharmaceutically acceptable salt thereof.

12 . The preparation of claim 1 , the polymer comprising less than about 0.5 wt % of a monomer of formula (V):

or a pharmaceutically acceptable salt thereof.

13 . A kit comprising a preparation, the preparation comprising a polymer comprising a monomer of formula (I):

or a pharmaceutically acceptable salt thereof, wherein leachable tin is present in the preparation at a level within a range of about 0 ppm to about 150 ppm, and the kit further comprising a container that stores the polymer comprising monomer of formula (I) under inert gas.

14 . The kit of claim 13 , comprising any one of the preparations of claims 2 - 12 .

15 . The kit of claim 13 , wherein the purified polymer comprising monomer of formula (I), or salt thereof, is least 98 wt % pure, for at least six months at −20° C.

16 . The kit of claim 13 , wherein the kit maintains leachable tin content at a level of less than 150 ppm for at least six months at −20° C.

17 . The kit of claim 13 , wherein the kit maintains leachable tin content at a level of less than 20 ppm for at least nine months at −20° C.

18 . The kit of claim 13 , comprising less than 1.5 wt % water relative to the wt % of the preparation.

19 . The kit of claim 13 , comprising less than 1.0 wt % water relative to the wt % of the preparation.

20 . A pharmaceutical composition comprising:

(a) a compound of formula (VI):

or pharmaceutically acceptable salts thereof,

wherein R 1 is a radioisotopic label, and

the compound of formula (VI) is formed by contacting a radioisotope of a halogen ion with a preparation of a polymer comprising monomer of formula (I):

or a pharmaceutically acceptable salt thereof, the preparation of the polymer comprising monomer of formula (I) comprising leachable tin at a level of 0 ppm to 150 ppm; and

(b) a pharmaceutically acceptable carrier, adjuvant, or vehicle.

21 . The pharmaceutical composition of claim 20 , comprising the preparation of claim 2 .

22 . The pharmaceutical composition of claim 20 , wherein the radioisotope of a halogen ion is fluoride, bromide, iodide or astatine.

23 . The pharmaceutical composition of claim 20 , wherein the radioisotope of a halogen ion is 123 I, 124 I, 125 I or 131 I.

24 . The pharmaceutical composition of claim 20 , wherein the radioisotope of a halogen ion is 211 At.

25 . A pharmaceutical composition comprising:

(a) meta-iodobenzylguanidine (MIBG):

or a pharmaceutically acceptable salt thereof, wherein MIBG is formed by contacting an iodide salt with a preparation of a polymer comprising monomer of formula (I):

or a pharmaceutically acceptable salt thereof, the preparation of the polymer comprising monomer of formula (I) comprising leachable tin at a level of 0 ppm to 150 ppm; and

(b) a pharmaceutically acceptable carrier, adjuvant, or vehicle.

26 . The pharmaceutical composition of claim 25 , comprising the preparation of claim 2 .

27 . The pharmaceutical composition of claim 25 , wherein not more than about 0.5 wt % meta-iodobenzylamine (MIBA):

or a pharmaceutically acceptable salt thereof, is present in the composition.

28 . The pharmaceutical composition of claim 25 , wherein not more than about 0.5 wt % meta-iodobenzylbiguanidine (MIBBG):

or a pharmaceutically acceptable salt thereof, is present in the composition.

29 . The pharmaceutical composition of claim 25 , wherein not more than about 0.5 wt % meta-hydroxybenzylguanidine (MHBG):

or a pharmaceutically acceptable salt thereof, is present in the composition.

30 . The pharmaceutical composition of claim 25 , wherein not more than about 0.5 wt % meta-iodobenzylamine (MIBA), meta-iodobenzylbiguanidine (MIBBG), and/or meta-hydroxybenzylguanidine (MHBG):

or pharmaceutically acceptable salts of any thereof, is present in the composition.

31 . A pharmaceutical composition comprising:

a compound of formula (VI):

or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle;

wherein R 1 is a radioisotopic label;

the pharmaceutical composition comprising leachable tin at a level of 0 ppm to 150 ppm.

32 . A pharmaceutical composition comprising:

meta-iodobenzylguanidine (MIBG):

or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle;

the pharmaceutical composition comprising leachable tin at a level of 0 ppm to 150 ppm.

33 . A method for preparing a purified composition of a polymer comprising monomer of formula (I):

or a pharmaceutically acceptable salt thereof, the method comprising the steps of:

solvent-treating a preparation comprising the polymer or pharmaceutically acceptable salt thereof, by contacting the preparation with a solvent, and then removing substantially all of the solvent so that a solvent-depleted material comprising the polymer, or pharmaceutically acceptable salt thereof, is generated; and

subjecting the solvent-depleted material to vacuum, and to a temperature within a range of about 30° C. to about 50° C.,

the subjecting being performed under conditions and for a time sufficient so that not more than about 150 ppm of leachable tin is present and, therefore, a purified composition of the polymer, or pharmaceutically acceptable salt thereof, has been produced.

34 . The method of claim 33 , wherein the solvent is or comprises an alcohol.

35 . The method of claim 34 , wherein the alcohol is or comprises ethanol.

36 . The method of claim 33 , wherein the step of solvent-treating the preparation comprises first and second solvent-treating steps, performed with first and second solvents, wherein the first solvent is an aqueous alcohol and the second solvent is an anhydrous alcohol.

37 . The method of claim 36 , wherein the first solvent is aqueous alcohol and the second solvent is anhydrous ethanol.

38 . The method of claim 33 , the purified composition comprising less than 1.5 wt % water relative to the wt % of the composition.

39 . The method of claim 33 , the purified composition comprising less than 1.0 wt % water relative to the wt % of the composition.

40 . The method of claim 33 , further comprising a step of: storing the purified composition under an inert gas.

41 . A method for preparing meta-iodobenzylguanidine (MIBG):

or a pharmaceutically acceptable salt thereof, the method comprising steps of:

contacting an iodide salt with a preparation comprising a polymer comprising monomer of formula (I):

or a pharmaceutically acceptable salt thereof, the preparation being substantially free of leachable tin such that leachable tin is present in the preparation at a level below 150 ppm.

42 . The method of claim 41 , wherein the step of contacting comprises contacting with a preparation as set forth in claim 2 .

43 . The method of claim 41 , wherein the iodide salt is sodium 1-131 iodide.

44 . A method comprising administering to a subject a pharmaceutical composition comprising:

(a) meta-iodobenzylguanidine (MIBG):

or a pharmaceutically acceptable salt thereof, wherein MIBG is formed by contacting an iodide salt with a preparation of a polymer comprising monomer of formula (I):

or a pharmaceutically acceptable salt thereof, the preparation of the polymer comprising monomer of formula (I) comprising leachable tin at a level of 0 ppm to 150 ppm;

(b) a pharmaceutically acceptable carrier, adjuvant, or vehicle.

45 . The method of claim 44 , wherein the pharmaceutical composition comprises leachable tin at a level of 0 ppm to 150 ppm upon administration.