Method of preparing rhenium-tricarbonyl complex and its precursor

Abstract

Disclosed herein is a method of preparing a 188Re-tricarbonyl complex for radiopharmaceutical use and of preparing a precursor thereof, and a contrast agent using the same. Particularly, this invention provides a method of preparing a 188Re-tricarbonyl precursor by reacting perrhenate with borane-ammonia (BH3.NH3), potassium boranocarbonate (K2[H3BCO2]) and phosphate in the presence of borohydride exchange resin as a reducing agent, and a method of preparing a 188Re-tricarbonyl complex by reacting the 188Re-tricarbonyl precursor with a ligand. According to the method of this invention, the borohydride exchange resin is used as a reducing agent and as an anion scavenger, thereby obtaining the 188Re-tricarbonyl precursor and complex having high radiolabeling yield and high purity. In addition, the 188Re-tricarbonyl complex can be used as a contrast agent having excellent plasma stability.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other objects, features and advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

FIG. 1 shows an HPLC chromatogram of ¹⁸⁸Re-tricarbonyl precursor and Na¹⁸⁸ReO₄ prepared in accordance with the present invention;

FIG. 2 shows an HPLC chromatogram of ^99mTc-tricarbonyl precursor prepared in accordance with the present invention;

FIG. 3 shows a result of paper electrophoresis of ¹⁸⁸Re-tricarbonyl precursor prepared in accordance with the present invention;

FIG. 4 shows an HPLC chromatogram of ¹⁸⁸Re-tricarbonyl histidine complex prepared in accordance with the present invention;

FIG. 5 shows an HPLC chromatogram of ^99mTc-tricarbonyl histidine complex prepared in accordance with the present invention; and

FIG. 6 shows a schematic view of borohydride exchange resin used as a solid-phase reducing agent and as an anion scavenger.

Claims

1. In a method of preparing a 188Re-tricarbonyl precursor by mixing perrhenate with borane-ammonia (BH3.NH3), potassium boranocarbonate (K2[H3BCO2]) and phosphate to react, a method of preparing a 188Re-tricarbonyl precursor using borohydride exchange resin serving as a reducing agent, the method being represented by Scheme 1 below:

2. The method as set forth in claim 1, wherein the reaction to prepare the 188Re-tricarbonyl precursor is conducted at 55-65° C. for 10-20 min.

3. The method as set forth in claim 1, wherein the borohydride exchange resin is used in an amount of 3-5 mg, based on 50 MBq of sodium perrhenate.

4. The method as set forth in claim 1, wherein the potassium boranocarbonate is used in an amount of 3-4 mg, based on 50 MBq of sodium perrhenate.

5. The method as set forth in claim 1, wherein the borane-ammonia is used in an amount of 3-4 mg, based on 50 MBq of sodium perrhenate.

6. A method of preparing a 188Re-tricarbonyl complex, comprising: mixing and reacting perrhenate with borane-ammonia (BH3.NH3), potassium boranocarbonate (K2[H3BCO2]) and phosphate in the presence of borohydride exchange resin serving as a reducing agent to prepare a 188Re-tricarbonyl precursor; andreacting the 188Re-tricarbonyl precursor with a ligand to prepare a 188Re-tricarbonyl complex, the method being represented by Scheme 2 below:

7. The method as set forth in claim 6, wherein the ligand is any one selected from the group consisting of nitrido, glucoheptonate, L-cysteine, L-cysteine-hydrochloric acid-water, histidine, diaminedisulfide, dimercaptosuccinic acid, thio-β-D-glucose, methylene diphosphate, diethylenetriaminepentaacetic acid, and N-[2-(2-((triphenylmethyl)thio)ethyl)acetyl]-S-(triphenylmethyl)-2-aminoethanethiol.

8. The method as set forth in claim 6, wherein the reaction to prepare the 188Re-tricarbonyl complex is conducted at 70-80° C. for 25-35 min.