Patent EP-2546839-A1 (EP)
Inventor: MARX SEBASTIAN DR
IPC: G21G1/00
Filed: 2012-04-04
Abstract: Producing carrier-free and ultra-pure lutetium-177 compounds for medical and/or diagnostic purposes from ytterbium-176 compounds irradiated with thermal neutrons, comprises: (a) loading a first column (VS1), which is packed with a cation exchange material containing starting materials dissolved in mineral acid, (b) connecting output of first column with input of a second column (S1), (c) applying gradient of water and a complexing agent, (d) detecting the radioactivity dose to detect an elution of lutetium-177 compounds, (e) loading final separating column, and (f) eluting lutetium-177 ions. Producing carrier-free and ultra-pure lutetium-177 compounds for medical and/or diagnostic purposes from ytterbium-176 compounds irradiated with thermal neutrons, comprises: (a) loading a first column (VS1), which is packed with a cation exchange material containing the starting materials dissolved in the mineral acid, replacing the protons of the cation exchange material for ammonium ions using a solution of ammonium chloride, and rinsing the cation exchange material of the first column with water, where the end products of the neutron irradiation comprise a mixture of the lutetium-177 and ytterbium-176 in a mass ratio of 1:10 2>-1: 10 1> 0>, are used as the starting materials, and the starting materials, which are insoluble in water, are converted into a soluble form by mineral acids, (b) connecting the output of the first column with the input of a second column, which is also packed with cation exchange material, (c) applying a gradient of water and a complexing agent including alpha -hydroxyisobutyrate (HIBA), citric acid, citrate, butyric acid, butyrate, EDTA, ethylene glycol tetraacetic acid (EGTA), and ammonium ions, starting from 100% of water-0.2 M complexing agent to the input of the first column to elute lutetium-177 compounds of the first and the second column, (d) detecting the radioactivity dose at the output of the second column, to detect an elution of lutetium-177 compounds, collecting a first eluate of lutetium-177 compounds from output of the second column in a container (F3), and protonating the complexing agent to make them ineffective for the complex formation with lutetium-177 ions, (e) loading a final separating column, which is packed with cation exchange material, by continuous propagation of the acidic lutetium-177 eluate obtained from the step (d) to the input of the final separating column, washing the complexing agent with dilute mineral acid at a concentration of less than 0.1 M, removing foreign metal ion traces from the lutetium-177 solution by washing the cation exchange material of the final separating column with a mineral acid of different concentrations of 0.1-2.5 M, and (f) eluting the lutetium-177 ions from the final separating column by a highly concentrated mineral acid of 3-12 M, collecting the ultra-pure lutetium-177 eluate in an evaporation system, and removing the mineral acid by evaporation; or steps (a)-(d), (e1) continuously transporting the acidic lutetium-177 eluate from step the (d) to the input of a third column (VS2), which is packed with the cation exchange material, where the cation exchange material is present in protonated form by the loading with the acidic lutetium-177 eluate, replacing the protons of the cation exchange material for ammonium ions using a solution of ammonium chloride, and rinsing the cation exchange material of the third column with water, (f1) connecting the output of the third column with the input of a fourth column (S2), which is packed with cation exchange material, (g) applying a gradient of water and complexing agent including HIBA, citric acid, citrate, butyric acid, butyrate, EDTA, EGTA, and ammonium ions, starting from 100% of water-0.2 M complexing agent to the input of the third column, (h) detecting the radioactivity dose at the output of the fourth column, to detect elution of lutetium-177 compounds, collecting a second eluate of lutetium-177 compounds from output of the third column in a container, and protonating the complexing agent to make them ineffective for the complex formation with lutetium-177 ions, (i) loading a fifth column, which is packed with cation exchange material, by continuous propagation of the acidic lutetium-177 eluate obtained from the step (h) to the input of the fifth column, washing the complexing agent with dilute mineral acid at a concentration of less than 0.1 M, removing foreign metal ion traces from the lutetium-177 solution by washing the cation exchange material of the fifth column with mineral acid of different concentrations of 0.1-2.5 M, and (j) eluting the lutetium-177 ions from the fifth column by a concentrated mineral acid of 1-12 M, collecting the ultra-pure lutetium-177 eluate in the evaporation system, and removing the mineral acid by evaporation. An independent claim is also included for carrier-free lutetium-177 compound produced by the above mentioned method.