Serotonin transporters in the midbrain of Parkinson's disease patients: a study with 123I-beta-CIT SPECT.
In Parkinson's disease (PD), both neuropathologic and biochemical studies suggest that serotonin (5-hydroxytryptamine [5-HT]) neurons are affected by the disease process. The integrity of 5-HT transporters was assessed in PD patients with SPECT using 2beta-carbomethoxy-3beta-(4-(123)I-iodophenyl)tropane ((123)I-beta-CIT), which binds with high affinity to both dopamine (DA) and 5-HT transporters.


METHODS
Forty-five PD patients at relatively early stages (mean Hoehn-Yahr stage, 2.0 +/- 0.7; range, 1-3) and 7 age-matched healthy control subjects had 15 scans over a 24-h period after injection of (123)I-beta-CIT using a 3-head SPECT system. In the midbrain, the 5-HT transporter parameter k(3)/k(4) was estimated by 3 noninvasive methods: pseudoequilibrium ratio (R(PE)) method, area ratio (R(A)) method, and a modified graphic method that derives the ratio of ligand distribution volumes (R(V)). Striatal V(3)", the DA transporter parameter that is equivalent to k(3)/k(4), was measured using the images acquired at 24 h after tracer injection. All measures were derived using the cerebellum as the reference region.


RESULTS
In control subjects, the (123)I-beta-CIT activity in the midbrain reached a peak at 91 +/- 21 min after injection and then washed out at a slow rate (1.1%/h +/- 0.5%/h). The peak specific uptake in the midbrain occurred at 315 +/- 46 min. In PD patients, the temporal patterns of the midbrain and cerebellar activity were not significantly different from those in control subjects. None of midbrain R(PE), R(A), and R(V) was significantly different between control subjects and PD patients, whereas striatal V(3)" was bilaterally reduced in all patients, being 32% lower than that of the control subjects (P = 0.002). In PD patients, none of the midbrain outcome measures was significantly correlated with either striatal V(3)" or motor or nonmotor symptom ratings, including the Hoehn-Yahr stage and the Unified Parkinson's Disease Rating Scale scores. When the studies of 7 PD patients with depression were analyzed separately, none of the midbrain outcome measures in these patients either was different significantly from control values or correlated with the Hamilton Depression Rating Scale score.


CONCLUSIONS
These results suggest that DA and 5-HT transporters are differentially affected in PD, and 5-HT transporters in the midbrain region may not be affected in relatively early stages of PD. Alternatively, 5-HT transporters in the remaining neurons may be upregulated, thus raising the midbrain 5-HT transporter density to almost normal levels.
Kim
Sang Eun
SE
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. sekim@smc.samsung.co.kr
Choi
Joon Young
JY
Choe
Yearn Seong
YS
Choi
Yong
Y
Lee
Won Yong
WY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine