Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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A new efficient route for synthesis of R,R- and S,S-hexamethylpropyleneamine oxime for labeling with technetium-99m

  • Vinay Kumar Banka (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine) ;
  • Young Ju Kim (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine) ;
  • Yun-Sang Lee (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine) ;
  • Jae Min Jeong (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine)
  • Received : 2020.12.17
  • Accepted : 2020.12.29
  • Published : 2020.12.31
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Abstract

[99mTc]Tc-Hexamethylpropylene amine oxime (HMPAO) is currently used as a regional cerebral blood flow imaging agent for single photon emission computed tomography (SPECT). The HMPAO ligand exists in two isomeric forms: d,l and meso showing different properties in vivo. Later studies indicated that brain uptake patterns of 99mTc-complexes formed from separated enantiomers differed. Separation of enantiomers is difficult by fractional crystallizations method. Usually, the substance is obtained in low chemical yield in a time-consuming procedure. Furthermore, the final product still contains some impurity. So we have developed new efficient route for synthesis of R,R- and S,S-HMPAO enantiomeric compounds in 6-steps. Nucleophilic substitution (SN2) reactions of 2,2-dimethylpropane-1,3-diamine either with S- (1a) or R-methyl2-chloropropanoate (1b) were performed to produce compounds R,R- (2a) or S,S-isomer (2b) derivatives protected with benzylchloroformate (Cbz), respectively. And then Weinreb amide and methylation reaction using Grignard reagent, oxime formation with ketone group and deprotectiion of Cbz group by hydrogenolysis gave S,S- (7a) or R,R-HMPAO (7b), respectively. Entaniomeric compounds were synthesied with high yield and purity without any undesired product. The 7a or 7b kits containing 10 ㎍ SnCl2-2H2O were labeled with 99mTc with high radiolabeling yield (90%).

Keywords

Acknowledgement

This research was supported by National R&D Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 1711026888 and NRF-2016M2C2A1937981) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C3093). This method was reported as Korean patent (Application No. 10-2016-0075232; Registration No. 10-1863795) by FNG Research Ltd.

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