Method of producing and refining carrier-free lutetium-177 using chromatography
The present invention relates to a method of producing and refining carrier-free lutetium-177 using chromatography, and more specifically to a method of producing and refining carrier-free lutetium 1-77 using chromatography having excellent resolution of lutetium and ytterbium without a concentration gradient of an eluent.
1 . A method for separating carrier-free lutetium-177 (Lu-177), which sequentially performs chromatography for a mixture comprising a compound of ytterbium and lutetium-177 (Lu-177) produced by irradiating neutrons at a compound of ytterbium-176 (Yb-176) as a target by 2 columns below:
1) separation column: a separation column with a cation exchange resin as a stationary phase, the separation column being filled with the stationary phase and being saturated with a first eluent comprising primary aminium ions and a chelating agent, and the first eluent being used as a mobile phase in the separation column; and
2) purification column: a purification column with the cation exchange resin as a stationary phase, and impregnated with water, wherein the first eluent is introduced from the separation column into the purification column
wherein the first eluent is a single eluent without a concentration gradient.
2 . The method of claim 1 , wherein lutetium-177 (Lu-177) is eluted first in the separation column, and then ytterbium (Yb) is eluted from the separation column.
3 . The method of claim 2 , wherein when lutetium-177 is eluted from the separation column, the first eluent comprising the eluted lutetium-177 is introduced into the purification column, and
wherein when the separation of lutetium-177 is completed or when ytterbium is eluted from the separation column, a second eluent comprising at least one of primary to quaternary aminium ions and a chelate agent is used as a mobile phase, and the ytterbium from the separation column is introduced into a separate column to perform chromatography to obtain ytterbium.
4 . The method of claim 3 , wherein the concentration of the chelate agent and the primary to quaternary aminium ions of the second eluent is higher than that of the first eluent.
5 . The method of claim 3 , wherein the concentration of the chelating agent in the second eluent is 0.1M to 1.0M.
6 . The method of claim 1 , wherein the cation exchange resin comprises at least one selected from a sulfate group (—SO 3 H), a phosphate group (—OP(O)(OH) 2 or —P(O)(OH) 2 ) and a carboxyl group (—C(O)OH) in an organic, inorganic or organic-inorganic mixture support.
7 . The method of claim 1 , wherein the primary aminium ions have C 1 to C 8 linear or branched alkyl group substituted or unsubstituted with a hydrophilic functional group.
8 . The method of claim 7 , wherein the hydrophilic functional group is each independently one selected from a hydroxyl group, a carbonyl group, an amine group, a carboxyl group, an ester group, an alkoxy group, an amide group, an imine group, an oxime group, a thiol group, a sulfide group, a sulfoxide group, a thioketone group and a thioester group.
9 . The method of claim 1 , wherein the chelating agent is a compound of C 2 to C 12 monocarboxylic acid, dicarboxylic acid, tricarboxylic acid or tetracarboxylic acid which further comprises a hydrophilic functional group other than a carboxyl group, or a salt thereof.
10 . The method of claim 9 , wherein the chelating agent is 2-hydroxyisobutyric acid (2-HIBA).
11 . The method of claim 1 , wherein the concentration of the chelating agent in the first eluent is 0.01M to 0.5M.
12 . The method of claim 1 , wherein the concentration of the aminium ion in the first eluent is 0.01M to 1.0M.
13 . The method of claim 1 , wherein a purification step by the purification column introduces a second eluent comprising carrier-free lutetium-177 eluted in the separation column into the purification column, and comprises the steps of:
a) eluting the chelating agent and the primary aminium ions included in the first eluent using an organic or inorganic acid having a concentration of 0.1M to 2M as a mobile phase; and
b) subsequently eluting carrier-free lutetium-177 with an organic or inorganic acid having a concentration of 3M to 12M as a mobile phase.