n-iodoallyl-2-carbomethoxy-3-(4-fluorophenyl)tropane and Disease-Models--Animal

This study used the dopamine transporter (DAT) probe, [(123)I]-2β-carbomethoxy-3β-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane ([(123)I]altropane), to assess the DAT levels in the 6-hydroxydopamine rat model of Parkinson's disease. We sought to assess if the right to left [(123)I]altropane striatal ratios correlated with dopamine content in the striatum and substantia nigra and with behavioural outcomes.. [(123)I]altropane images taken pre- and postlesion were acquired before and after the transplantation of neural stem/progenitor cells. The images obtained using [(123)I]altropane and single photon emission computed tomography (SPECT) were compared with specific behavioural tests and the dopamine content assessed by high-performance liquid chromatography.. [(123)I]altropane binding correlated with the content of dopamine in the striatum; however, [(123)I]altropane binding did not correlate with the dopamine content in the substantia nigra. There was a significant correlation of altropane ratios with the cylinder test and the postural instability test, but not with amphetamine rotations. The low coefficient of determination (r(2)) for these correlations indicated that [(123)I]altropane SPECT was not a good predictor of behavioural outcomes.. Our data reveal that [(123)I]altropane predicts the integrity of the striatal dopamine nerve terminals, but does not predict the integrity of the nigrostriatal system. [(123)I]altropane could be a useful marker to measure dopamine content in cell replacement therapies; however, it would not be able to evaluate outcomes for neuroprotective strategies.

Topics: Animals; Behavior, Animal; Biomarkers; Cocaine; Disease Models, Animal; Dopamine; Dopamine Plasma Membrane Transport Proteins; Iodine Radioisotopes; Neostriatum; Neural Stem Cells; Oxidopamine; Parkinson Disease; Rats; Rats, Sprague-Dawley; Stem Cell Transplantation; Tomography, Emission-Computed, Single-Photon