SPECT imaging of the α4β2 nicotinic receptor using [5‐¹²³I]A85380

Nickel‐Mediated Radioiodination of Aryl and Heteroaryl Bromides: Rapid Synthesis of Tracers for SPECT Imaging

“…The more traditional two‐step synthesis of 7 involving formation of an organotin intermediate from 6 followed by an oxidative [ 123 I] iodo‐destannylation reaction produces isolated 7 in comparable radiochemical yields (40–61 %) and radiochemical purity (>95 %) but generally with higher specific activities (1.7–149 Ci μmol −1 ) 7. 8, 9a However, the synthesis of the organotin precursor from 6 gives yields of only 42–44 %,8, 22 and subsequent iodo‐destannylation using chloramine‐T as the oxidant produces a non‐radioactive chloropyridine by‐product, which decomposes further during the radiochemical synthesis to give a nonseparable, highly potent nAChR ligand 7. Therefore, the use of our single‐step, nickel‐mediated radioiodination gives 7 in significantly higher overall yield without any purification issues.…”

Molecular tracers for the PET and SPECT imaging of disease

“…76 5-[ 123 I]-A85380 82 has been radiolabelled via electrophilic iododestannylation of the corresponding Boc-protected trimethylstannyl precursor 80, using chloramine-T as an oxidising agent (Scheme 23). 77 The Boc-protecting group was removed using acid mediated conditions. 5-[ 123 I]-A85380 82 was obtained with a high radiochemical yield of 61% and a specific activity of 149 Ci mmol À1 .…”

Nickel‐Mediated Radioiodination of Aryl and Heteroaryl Bromides: Rapid Synthesis of Tracers for SPECT Imaging

“…[7][8][9][10] Optimal reaction conditions for a nickel(0)-mediated halogen-exchange reaction were explored using 2-bromonaphthalene 1 a as a substrate (Table 1). As well as exploring the scope of this transformation for the preparation of a range of [ 125 I]-labeled compounds, we also demonstrate its application for the synthesis of 5-[ 123 I]-A85380, a SPECT tracer used for imaging neuronal nicotinic acetylcholine receptors (nAChR) in humans.…”

“…As well as exploring the scope of this transformation for the preparation of a range of [ 125 I]-labeled compounds, we also demonstrate its application for the synthesis of 5-[ 123 I]-A85380, a SPECT tracer used for imaging neuronal nicotinic acetylcholine receptors (nAChR) in humans. [7][8][9][10] Optimal reaction conditions for a nickel(0)-mediated halogen-exchange reaction were explored using 2-bromonaphthalene 1 a as a substrate (Table 1). Nickel(0)-mediated halogen-exchange reactions have been reported previously using either zinc [11a] or an electrochemical cell [11b] to reduce a Ni II catalyst to the active Ni 0 species.…”

“…The nickel-mediated radioiodination reaction was also employed for the preparation of 5-[ 125 I]-A85380 2 j, a SPECT tracer used for imaging neuronal nicotinic acetylcholine receptors (nAChR) in humans. [7][8][9][10] Radioiodination of (2S)-3-bromo-5-{[1-(tert-butoxycarbonyl)-2-azetidinyl]-methoxy}pyridine followed by removal of the tert-butyloxycarbonyl (Boc) protecting group mediated by trifluoroacetic acid (TFA) gave 5-[ 125 I]-A85380 2 j in 95 % radiochemical yield. Some limitations using the nickel-mediated radioiodination reaction were also discovered.…”