Method for purification of 225AC from irradiated 226RA-targets

Patent metadata

Field	Value
Publication number	US-9790573-B2
Application number	US-201615359053-A
Country	US
Kind code	B2
Filing date	Nov 22, 2016
Priority date	Feb 21, 2006
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

The present invention describes a method for purification of 225 Ac from irradiated 226 Ra-targets provided on a support comprising a leaching treatment of the 225 Ra-targets for leaching essentially for the entirety of 223 Ac and 226 Ra with nitric or hydrochloric acid, followed by a first extraction chromatography for separating 225 Ac from 226 Ra and other Ra-isotops and a second extraction chromotography for separating 225 Ac from 210 Po and 210 Pb. The finally purified 225 Ac can be used to prepare compositions useful for pharmaceutical purposes.

First claim

The invention claimed is:

1. A method for purification of 225 Ac from irradiated 226 Ra-targets provided on a support, comprising the following steps:
a) leaching 225 Ac and 226 Ra from one or more 226 Ra-targets with a nitric acid solvent in a refluxing/distillation arrangement to generate one or more 225 Ac and 226 Ra containing extracts, wherein said nitric acid solvent has a concentration range of about 0.001 M to about 2 M;
b) concentrating the 225 Ac and 226 Ra containing extracts, wherein the concentrating results in a 225 Ac and 226 Ra containing extract having a concentration of about 1.5 M to about 10 M of HNO 3 ;
c) separating 225 Ac from 226 Ra and other Ra isotopes by means of at least one first extraction chromatography with a solid support material having a first extractant system coated thereon, comprising at least one compound in accordance with general formula IA,

wherein in formula IA:
R1a, R2a, R3a, R4a independently is octyl or 2-ethylhexyl;

d) allowing the 226 Ra to flow through and then eluting 225 Ac retained on the solid support with nitric acid having a concentration between about 0.01M and about 0.3M or with hydrochloric acid having a concentration between about 0.05M and about 1M;
e) separating 225 Ac from 210 Po and 210 Pb by means of at least one second extraction chromatography with a solid support material having a second extractant system coated thereon, comprising at least one compound in accordance with general formula III in at least one compound in accordance with general formula IV,

wherein in formula III:
R8 and R9 independently is H, C 1 -C 6 alkyl, or t-butyl;
and

wherein in formula IV:
R10 is C 4 to C 12 alkyl;

f) using 2M HCl as mobile phase; and
g) recovering 225 Ac as a flow-through separately from 210 Po and 210 Pb, which are retained on the solid support.

2. A method for purification of 225 Ac from irradiated 226 Ra-targets provided on a support, comprising the following steps:
a) leaching 225 Ac and 226 Ra from one or more 226 Ra-targets with a nitric acid solvent in a refluxing/distillation arrangement to generate one or more 225 Ac and 226 Ra containing extracts, wherein said nitric acid solvent has a concentration range of about 0.001 M to about 2 M;
b) concentrating the 225 Ac and 226 Ra containing extracts, wherein the concentrating results in a 225 Ac and 226 Ra containing extract having a concentration of about 1.5 M to about 10 M of HNO 3 ;
c) separating 225 Ac from 226 Ra and other Ra isotopes by means of at least one first extraction chromatography with a solid support material having a first extractant system coated thereon, comprising at least one compound in accordance with general formula IB,

d) allowing the 226 Ra to flow through and then eluting 225 Ac retained on the solid support with nitric acid having a concentration between about 0.02 M and about 0.1 M;
e) separating 225 Ac from 210 Po and 210 Pb by means of at least one second extraction chromatography with a solid support material having a second extractant system coated thereon, comprising at least one compound in accordance with general formula III in at least one compound in accordance with general formula IV,

wherein in formula III:
R8 and R9 independently is H, C 1 -C 6 alkyl, or t-butyl;
and

wherein in formula IV:
R10 is C 4 to C 12 alkyl;

f) using 2M HCl as mobile phase; and
g) recovering 225 Ac as a flow-through separately from 210 Po and 210 Pb which are retained on the solid support.

3. The method of any one of claims 1 to 2 , wherein the support is a metal, and is selected from the group consisting of Aluminum or Aluminum alloys, passivated Aluminum, anodized Aluminum, coated Aluminum, Aluminum coated with an element of a Platinum group, precious metals, elements from a Platinum group; and mixtures thereof.

4. The method of any one of claims 1 to 2 , wherein the second extractant system is a crown ether in accordance with formula V:

in 1-octanol.

5. The method of any one of claims 1 to 2 , wherein the second extractant system is 4,4′-bis(t-butylcyclohexano)-18-crown-6 in 1-octanol.

6. The method of any one of claims 1 to 2 , wherein the second extractant system is 4,5′-bis(t-butylcyclohexano)-18-crown-6 in 1-octanol.

7. The method of any one of claims 1 to 2 , wherein the first extraction chromatography of step c) is repeated one or more times.

8. The method of any one of claims 1 to 2 , wherein the second extraction chromatography of step e) is repeated one or more times.

9. The method of any one of claims 1 to 2 , further comprising removing Rn from the support or the 225 Ac and 226 Ra containing extract during step a).

10. The method of claim 9 , wherein the Rn is removed by means of a first alkaline trap to neutralize acidic vapours, a subsequent silica trap to absorb water, and a final activated coal trap.

11. The method of any one of claims 1 to 2 , further comprising a step of recovering a 226 Ra flow-through of step d).

12. The method of any one of claims 1 to 2 , further comprising a step of eluting 210 Po from the solid support of the second extraction chromatography in step g) by means of concentrated nitric acid or concentrated hydrochloric acid.

13. The method of any one of claims 1 to 2 , wherein a fraction of a purification step is examined by means of α- and/or γ-spectroscopy.

14. The method of any one of claims 1 to 2 , wherein a fraction of a purification step containing any one of:
a) 225 Ac;
b) Ra-isotopes;
c) 210 Po; and
d) 210 Pb
is subjected to an evaporation step.

15. The method of any one of claims 1 to 2 , further comprising a step of removing one or more organic impurities from a fraction of a purification step.

16. The method of any one of claims 1 to 2 , wherein the nitric acid solvent of step a) has a concentration of about 0.1M.

17. The method of any one of claims 1 to 2 , wherein the nitric acid solvent of step a) is used at a temperature of about 30 to 90° C.

18. The method of claim 10 , wherein the activated coal trap is cooled.

19. The method of any one of claims 1 to 2 , further comprising a step of eluting 210 Pb from the solid support of the second extraction chromatography in step g) by means of concentrated hydrochloric acid or EDTA.

20. The method of claim 14 , wherein the fraction is evaporated to a wet or a dry residue.

21. The method of claim 14 , wherein the fraction is redissolved.

22. The method of claim 15 , wherein the step of removing one or more organic impurities from a fraction of a purification step is performed by passing the fraction through a resin comprising a non-ionic acrylic ester polymer.

Assignees

• Actinium Pharmaceuticals Inc

Inventors

• Moreno Bermudez Josue Manuel
• Turler Andreas
• Henkelmann Richard
• Kabai Eva
• Huenges Ernst

Classifications

• G21G1/001

  Recovery of specific isotopes from irradiated targets · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K51/00

  Preparations containing radioactive substances for use in therapy or testing in vivo · CPC title

• G21G4/08

  specially adapted for medical application (radiation therapy using radioactive sources A61N5/10) · CPC title

• G21G2001/0089

  Actinium · CPC title