SPECT study of the nigrostriatal dopaminergic system in Huntington's disease.
OBJECTIVE
The pathological process of Huntington's disease (HD) preferentially targets spiny neurons in the striatum, with later involvement of the substantia nigra and other structures. The purpose of this study is to investigate the nigrostriatal dopaminergic system in a genetically confirmed HD family.


METHODS
We used single photon emission computed tomography (SPECT) with the radiotracers [(99m) Tc]TRODAT-1 and [123I]IBZM to study the binding potentials of dopamine transporter (DAT) and dopamine D2 receptors in the striatum of 3 symptomatic HD patients, 1 mutation-negative member of the HD family, and 7 healthy controls. Specific binding potentials were calculated as (striatum-occipital lobe)/occipital lobe.


RESULTS
Reduced binding potential of striatal dopamine D2 receptors was found in the 3 symptomatic HD patients. The DAT binding potential was reduced in 1 symptomatic HD patient. We also found that the more severe the clinical status, the lower the DAT and D2 receptor binding potentials, and the larger the bicaudate ratio.


CONCLUSIONS
We showed that the postsynaptic part of the nigrostriatal pathway was involved. The presynaptic part is usually not affected but could occur in very advanced cases. Our findings suggest that SPECT imaging of D2 receptors is useful for diagnosing and monitoring HD.
Department of Neurology, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan. wjh-wang@mail.nicku.edu.tw
Wen-Juh
WJ
Hwang
Wei-Jen
WJ
Yao
D000328:Adult; D001549:Benzamides / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014326:Tropanes / Q000493:pharmacokinetics
D001549:Benzamides; D050483:Dopamine Plasma Membrane Transport Proteins; D015609:Organotechnetium Compounds; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide