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

(123)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 (123)I-NKJ64, highlighting the advantages and disadvantages, pitfalls and solutions encountered while developing the final radiolabelling methodology.

The synthesis of (123)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).

Radioiodination of the Boc-protected trimethylstannyl precursor was achieved with an incorporation yield of 92±6%. Deprotection with 2 M HCl produced (123)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 (123)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 (123)I-NKJ64 during the high-performance liquid chromatography (HPLC) purification.

The radiosynthesis of (123)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 (123)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.