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)

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<p><b>Introduction:</b> <sup>123</sup>I-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 <sup>123</sup>I-NKJ64, highlighting the advantages and disadvantages, pitfalls and solutions encountered while developing the final radiolabelling methodology.</p> <p><b>Methods:</b> The synthesis of <sup>123</sup>I-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 <sup>123</sup>I-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 <sup>123</sup>I-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 <sup>123</sup>I-NKJ64 during the high-performance liquid chromatography (HPLC) purification.</p> <p><b>Conclusions:</b> The radiosynthesis of <sup>123</sup>I-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 <sup>123</sup>I-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
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 > Institute of Neuroscience and Psychology
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 (Online):1872-9614

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