Dopamine Receptor SPET Imaging in Parkinson’s Disease: A[¹²³l]-IBZM and [⁹⁹mTc]-HM-PAO Study

Abstract

Single photon emission tomography (SPET) with the novel ligand [¹²³I]-IBZM was used to image central dopamine D2 receptors in Parkinson’s disease (PD) patients. The aim was to assess basal ganglia (BG) receptor densities in relation to the response to L-dopa therapy. To better characterize the clinical potential of [¹²³I]-IBZM SPET, each patient underwent a second study with the regional perfusion tracer [^99mTc]-HM-PAO. Tracer activity ratios were calculated for caudate and putamen with mean activity over the cerebellar hemispheres as internal standard. In PD patients we found a significant decline of mean caudate [¹²³I]-IBZM activity, as compared with age-matched control subjects. However, when patients were grouped according to their therapeutic behavior, the [¹²³I]-IBZM uptake in BG ganglia regions of the PD patient group with a poor and fluctuating response to L-dopa was significantly reduced from mean values of patients with a sustained response to L-dopa therapy. [^99mTc]-HM-PAO caudate and putamen uptake indexes in PD were similar to control values, even in patients with deteriorated therapeutic response. Our results indicate that BG D2 receptor alterations in PD may contribute to the altered response to L-dopa.

Downregulation of Striatal Dopamine D2 Receptors in Advanced Parkinson’s Disease Contributes to the Development of Motor Fluctuation

“…Our finding that advanced PD patients with fluctuating levodopa response (Group III) had significantly decreased D2 receptor densities agrees with reports by Pizzolato et al [10, 11]. The mean disease duration for Group III in the present study was 9.2 years and the mean Hoehn & Yahr stage was 3.4.…”

“…The findings that continuous intravenous infusion of levodopa may reduce but will not eliminate motor fluctuations in many advanced PD patients support downregulation of dopamine receptors [18, 19]. The contribution of dopamine receptor downregulation to the development of motor fluctuation is clearly shown by (1) the observations of continuous intravenous dopaminergic therapy [18, 19], (2) the findings of the present and some previous SPECT/PET studies [10, 11, 12], and (3) the postmortem study [20]. …”

“…The present study and those of Pizzolato et al [10, 11] included more patients with unpredictable motor fluctuation than did the study of Antonini et al [7]. Prospective longitudinal studies on a population of PD patients would be most helpful for clarifying the long-term changes in striatal dopamine D2 receptor densities at different stages of levodopa response.…”

“…Both presynaptic [3, 4] and postsynaptic [5, 6] mechanisms have been reported to be important in the development of motor fluctuation. Previous studies with either 123 I-iodobenzamide single-photon emission computed tomography ( 123 I-IBZM SPECT) or 11 C-raclopride positron emission tomography ( 11 C-raclopride PET) have shown initial upregulation of striatal dopamine D2 receptors in the contralateral putamen of early-stage PD [7, 8, 9], and normal [7] or reduced [10, 11, 12] D2 receptor densities in fluctuating PD. The purpose of this cross-sectional study was to compare the postsynaptic D2 receptor densities in early levodopa-naïve PD, chronic PD with stable levodopa response, and advanced PD with fluctuating levodopa response to see if this would explain the postsynaptic mechanism’s contribution to the pathophysiology of motor fluctuation in advanced PD.…”

Clinical and [^99mTc]TRODAT-1/[¹²³I]IBZM SPECT Imaging Findings in Dopa-Responsive Dystonia

“…Dopamine D2 receptor densities are reported to be normal or elevated in DRD patients [10, 11], while [ 123 I]IBZM SPECT or [ 11 C]raclopride PET have shown initial upregulation of striatal dopamine D2 receptors in the contralateral putamen of early-stage idiopathic parkinsonism [12, 13], and normal [12]or reduced [14, 15, 16]D2 receptor densities in fluctuating idiopathic parkinsonism. We report the DAT ligand [ 99m Tc]TRODAT-1 and D2 receptor ligand [ 123 I]IBZM SPECT imaging findings and the long-term treatment course in a woman with DRD for 24 years.…”