Simplified Quantification Method for In Vivo SPECT Imaging of the Vesicular Acetylcholine Transporter with ¹²³I-Iodobenzovesamicol

Abstract

123 I-iodobenzovesamicol is a SPECT radioligand selective for the vesicular acetylcholine transporter (VAChT) and used to assess the integrity of cholinergic pathways in various neurologic disorders. The current noninvasive method for quantitative analysis of 123 Iiodobenzovesamicol, based on multilinear reference tissue model 2 (MRTM2), requires repeated scans for several hours, limiting its application in clinical trials. Our objective was to validate a simplified acquisition method based on a single 123 I-iodobenzovesamicol static scan preserving the quantification accuracy. Three acquisition times were tested comparatively to a kinetic analysis using MRTM2. Methods: Six healthy volunteers underwent a dynamic SPECT acquisition comprising 14 frames over 28 h and an MR imaging scan. MR images were automatically segmented, providing the volumes of 19 regions of interest (ROIs). SPECT datasets were coregistered with MR images, and regional time-activity curves were derived. For each ROI, a complete MRTM2 pharmacokinetic analysis, using the cerebellar hemispheres as the reference region, led to the calculation of a 123 I-iodobenzovesamicol-to-VAChT binding parameter, the nondisplaceable binding potential (BP ND-MRTM2 ). A simplified analysis was also performed at 5, 8, and 28 h after injection, providing a simplified BP ND , given as BP ND-t 5 C ROI − C cerebellar hemispheres / C cerebellar hemispheres , with C being the averaged radioactive concentration. Results: No significant difference was found among BP ND-5 h , BP ND-8 h , and BP ND-MRTM2 in any of the extrastriatal regions explored. BP ND-28 h was significantly higher than BP ND-5 h , BP ND-8 h , and BP ND-MRTM2 in 9 of the 17 regions explored (P , 0.05). BP ND-5 h , BP ND-8 h , and BP ND-28 h correlated significantly with BP ND-MRTM2 (P , 0.05; ρ 5 0. 99, 0.98, and 0.92, respectively). In the striatum, BP ND-28 h was significantly higher than BP ND-5 h and BP ND-8 h . BP ND-5 h differed significantly from BP ND-MRTM2 (P , 0.05), with BP ND-5 h being 43.6% lower. Conclusion: In the extrastriatal regions, a single acquisition at 5 or 8 h after injection provides quantitative results similar to a pharmacokinetic analysis. However, with the highest correlation and accuracy, 5 h is the most suitable time to perform an accurate 123 I-iodobenzovesamicol quantification. In the striatum, none of the 3 times has led to an accurate quantification.

123I-Iodobenzovesamicol SPECT Imaging of Cholinergic Systems in Dementia with Lewy Bodies

“…Because they demonstrate the existence of cholinergic damage in the superior and inferior parietal cortices, our results are in good agreement with these findings, except in the occipital regions, probably because of differences in the tracers used. From a physiologic point of view, VAChT density is very low in the occipital cortex (24,26), making a comparison of this structure in patients and control subjects with 123 I-iodobenzovesamicol difficult. Furthermore, noncholinergic (i.e., choline acetyltransferase-or VAChT-negative) but AChE-rich neurons (i.e., cholinoceptive neurons) are found in almost all parts of the brain (30), providing another explanation for the more widespread cortical alterations found in previous PET studies than in the present study.…”

“…For a healthy subject and a representative DLB patient, Figure 2 shows parametric images of simplified BP ND , a parameter reflecting the ratio of specific binding to nonspecific binding (26), calculated for the striatum and the thalamus from SPECT images obtained 8 h after injection.…”

“…The reference method for the noninvasive quantification of 123 Iiodobenzovesamicol data was used (24), that is, a complete multilinear reference tissue model pharmacokinetic analysis (25), with the cerebellar hemispheres as reference regions (26). This method allowed us to calculate the nondisplaceable binding potential (BP ND ) values for the binding of 123 I-iodobenzovesamicol to the vesicular acetylcholine transporter for each participant and each ROI.…”

Identification of Alzheimer’s Disease by Molecular Imaging: Progress and Prospects

“…In addition, the decrease in affinity was limited to the parietal lobe and occipital lobe in patients with Parkinson's disease (PD), but decreased in the whole cortex in patients with PD and AD. Therefore, this compound is also considered to be used to detect cholinergic neuronal degeneration, but its specificity and sensitivity for the diagnosis of AD need to be determined (56). Dopaminergic neurons are widely studied in diseases such as PD, schizophrenia, and drug abuse.…”