Development of the radiosynthesis of high-specific-activity ¹²³I-NKJ64

Tavares, A.A.S., Jobson, N.K., Dewar, D. , Sutherland, A. and Pimlott, S.L. (2011) Development of the radiosynthesis of high-specific-activity ¹²³I-NKJ64. Nuclear Medicine and Biology, 38(4), pp. 493-500. (doi: 10.1016/j.nucmedbio.2010.11.011)

Abstract

<p><b>Introduction:</b> ¹²³I-NKJ64, a reboxetine analogue, is currently under development as a potential novel single photon emission computed tomography radiotracer for imaging the noradrenaline transporter in brain. This study describes the development of the radiosynthesis of ¹²³I-NKJ64, highlighting the advantages and disadvantages, pitfalls and solutions encountered while developing the final radiolabelling methodology.</p> <p><b>Methods:</b> The synthesis of ¹²³I-NKJ64 was evaluated using an electrophilic iododestannylation method, where a Boc-protected trimethylstannyl precursor was radioiodinated using peracetic acid as an oxidant and deprotection was investigated using either trifluoroacetic acid (TFA) or 2 M hydrochloric acid (HCl).</p> <p><b>Results:</b> Radioiodination of the Boc-protected trimethylstannyl precursor was achieved with an incorporation yield of 92±6%. Deprotection with 2 M HCl produced ¹²³I-NKJ64 with the highest radiochemical yield of 98.05±1.63% compared with 83.95±13.24% with TFA. However, the specific activity of the obtained ¹²³I-NKJ64 was lower when measured after using 2 M HCl (0.15±0.23 Ci/µmol) as the deprotecting agent in comparison to TFA (1.76±0.60 Ci/µmol). Further investigation of the 2 M HCl methodology found a by-product, identified as the deprotected proto-destannylated precursor, which co-eluted with ¹²³I-NKJ64 during the high-performance liquid chromatography (HPLC) purification.</p> <p><b>Conclusions:</b> The radiosynthesis of ¹²³I-NKJ64 was achieved with good isolated radiochemical yield of 68% and a high specific activity of 1.8 Ci/µmol. TFA was found to be the most suitable deprotecting agent, since 2 M HCl generated a by-product that could not be fully separated from ¹²³I-NKJ64 using the HPLC methodology investigated. This study highlights the importance of HPLC purification and accurate measurement of specific activity while developing new radiosynthesis methodologies.</p>

• Item Type: Articles
• Keywords: Radiosynthesis, stability, specific activity, SPECT, 123I-NKJ64, noradrenaline transporter
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Pimlott, Dr Sally and Dewar, Dr Deborah and Sutherland, Professor Andrew
• Authors: Tavares, A.A.S., Jobson, N.K., Dewar, D., Sutherland, A., and Pimlott, S.L.
• Subjects: Q Science > QD Chemistry; R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Science and Engineering > School of Chemistry
• Journal Name: Nuclear Medicine and Biology
• Publisher: Elsevier Inc.
• ISSN: 0969-8051
• ISSN (Online): 1872-9614