SPECT tracer [123I]IBZM has similar affinity to dopamine D2 and D3 receptors

Abstract

Emission tomography investigations of the pathophysiological involvement of the cerebral dopaminergic transmitter system in the living human brain relies heavily on a careful selection of the most suitable radioligand. In recent years, many clinical studies have employed [(123)I]IBZM in SPECT studies. The aim of the present study was to characterize the binding of IBZM to dopaminergic receptor subtypes as a means of elucidating which receptor subtypes are visualized and examined by [(123)I]IBZM. The affinity of IBZM for each of the major human dopamine receptors (D1, D2(short), D3, D4(4. 2), and D5 receptor) was determined by competitive radioligand binding assay using membranes prepared from clonal cell lines expressing the different subtypes. Radioligands with high affinity for the D1(A) and D5 receptors ([(3)H]SCH-23390), dopamine D2(short) and D4(4.2) receptors ([(3)H]Spiroperidol), and dopamine D3 receptor ([(3)H]7-OH-DPAT) were used to measure specific binding. Corresponding unlabeled displacing ligands for determination of nonspecific binding were employed. Assays were performed at 25 degrees C. These experiments show that for IBZM K(i) values were 1.6 nM for dopamine D2(s) receptors and 2.2 nM for dopamine D3 receptors. There was no binding of IBZM to D1(A), D5, or D4(4.2) receptors. In conclusion, when [(123)I]IBZM is used as SPECT tracer, the studies reflect dopaminergic D2 as well as D3 receptor binding.

A comparison of D2 receptor specific binding in obese and normal‐weight individuals using PET with (N‐[11C]methyl)benperidol

“…The selectivity of [ 11 C]NMB for the D2R of the D2 receptor family over D3R (Karimi et al, ) might explain the differences between our results and previous studies. The PET radioligands used in previous obesity studies such as [ 11 C]raclopride (Haltia et al, ; Wang et al, ) and [ 18 F]fallypride (Dunn et al, ) and the SPECT radioligand [ 123 I] IBZM (de Weijer et al, ) do not distinguish well between D2 and D3 subtypes (Elsinga et al, ; Mukherjee et al, ; Videbaek et al, ). If D3R specific binding is altered in obesity, it could explain the difference between our finding and other studies with non‐specific D2/D3 radioligands.…”

“…These radioligands have important limitations. First, these radioligands do not distinguish between D2 (D2R) and D3 (D3R) receptor subtypes of the D2 dopamine receptor family (Elsinga et al, ; Mukherjee et al, ; Videbaek et al, ). D2R and D3R have different, although somewhat overlapping, distributions throughout the human brain (Beaulieu and Gainetdinov, ) and thus could have separate functional roles in reward‐related behaviors.…”

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

“…The DRD2 HIGH primarily mediate the effects of dopamine (George et al, 1985;Leff, 1995;Liu et al, 2000). In addition, the PET/SPECT signal from these radioligands consists of a mix of DRD2 and DRD3 binding (Halldin et al, 1995;Mukherjee et al, 1999;Narendran et al, 2006;Strange, 2001;Videbaek et al, 2000). Lastly, the receptor quantification has mostly been limited to the striatum owing to the low level of extra-striatal DRD2/3 receptors and low affinity of the radiotracers.…”

Rotation Radius Dependence of 123I-FP-CIT and 123I-IBZM SPECT Uptake Ratios: A Monte Carlo Study

“…Striatal uptake of 123 I-FP-CIT is reduced in idiopathic Parkinson disease patients, compared with healthy controls, and can be very low in advanced stages of the disease. The radiopharmacon 123 I-IBZM ( 123 I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide [ 123 I-Iolopride; GE Healthcare B.V.]) is a dopamine receptor antagonist that has a high affinity to D 2 -and D 3 -receptors (6,7). 123 I-IBZM SPECT is claimed to have a differential diagnostic value in the issue of idiopathic Parkinson disease or atypical parkinsonism (i.e., multiple-system atrophy or progressive supranuclear palsy) (8,9).…”