title: Development of the radiosynthesis of high-specific-activity 123I-NKJ64.
abstract: BACKGROUND
  (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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ Glasgow, UK. a.tavares.1@research.gla.ac.uk
authors.forename: Adriana Alexandre S
authors.initials: AA
authors.lastname: Tavares
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Jobson
authors.forename: Deborah
authors.initials: D
authors.lastname: Dewar
authors.forename: Andrew
authors.initials: A
authors.lastname: Sutherland
authors.forename: Sally L
authors.initials: SL
authors.lastname: Pimlott
mesh_terms: D004355:Drug Stability; D007462:Iodobenzenes / Q000138:chemical synthesis* / Q000737:chemistry; D013058:Mass Spectrometry; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry; D011854:Radiochemistry / Q000379:methods*; D013379:Substrate Specificity
chemical_list: C560257:2-((2-iodophenoxy)phenylmethyl)morpholine; D007462:Iodobenzenes; D009025:Morpholines