Spect imaging of dopamine transporters in human brain with iodine-123- fluoroalkyl analogs of β-CIT

Iodine-123-2β-carbomethoxy-3β-(4-iodophenyl)tropane (β-CIT) is a useful SPECT tracer for imaging the dopamine transporter. Its slow kinetics, however, necessitate imaging on the day after the injection. Two N-ω- fluoroalkyl analogs of β-CIT, the fluoropropyl and fluoroethyl compounds (β-CIT-FP and β-CIT-FE, respectively), characterized by faster kinetics in baboons, were tested in humans as potential tracers for the dopamine transporter. Four healthy volunteers were injected with [¹²³]-β-CIT-FP and another four were injected with [¹²³]β-CIT-FE. SPECT data were acquired for 1149 ± 590 min and 240 ± 30 min, respectively. Both tracers demonstrated high brain uptake (6.37% ± 0.37% and 7.8% ± 1.5% of the injected dose, respectively). Activity concentrated with time in the striatal area, reaching a peak within 30 min, with little or no washout for [¹²³]β-CIT-FP and a faster washout for [¹²³I]β-CIT-FE (14.7% ± 6.9%). Occipital and midbrain activity showed similar patterns, displaying a peak within 15 min and rapid washout, followed by stable levels at approximately 100 min for both tracers. The ratio of peak specific striatal- to-peak specific midbrain activity was 9.1 ± 1.8 for [¹²³I]β-CIT-FP and 7.7 ± 0.7 for [¹²³I]β-CIT-FE, showing high in vivo selectivity for the dopamine transporter. These preliminary results suggest that both compounds could be used as SPECT(labeled with ¹²³I) or PET (labeled with ¹⁸F) radiotracers to image the dopamine transporters in the living human brain.