Reference tissue models in the assessment of ¹¹C‐DTBZ binding to the VMAT2 in rat striatum: A test‐retest reproducibility study

Abstract

Dopaminergic PET imaging is a useful tool to assess the dopaminergic integrity and to follow-up longitudinal studies. The aim of this study was to evaluate the reliability and reproducibility of different reference tissue-based methods to determine the non-displaceable binding potential (BP ) as a quantitative measure of C-DTBZ binding to the VMAT2 in rat striatum using cerebellum as reference region. Eight healthy Wistar rats underwent two microPET scans at the age of 12 (test) and 20 weeks (retest). BP was determined using the simplified reference tissue model, Logan reference tissue model, and multilinear reference tissue models (MRTMo and MRTM2). Additionally, a striatal-to-cerebellar-ratio (SCR) analysis was performed. The reproducibility between the two scans was assessed using the interclass correlation coefficients (ICC) and the variability index. Repeatability indices showed acceptable ICC = 0.66 (SCR) to excellent ICC = 0.98 (MRTM2) reliability for this study and a variability ranging from 12.26% (SCR) to 3.28% (MRTM2). To the best of our knowledge, this is the first report on longitudinal studies for C-DTBZ in rats using reference tissue methods. Excellent intersubject and intrasubject reproducibility was obtained with the multilinear reference MRTM2, suggesting this as the best method to compare longitudinal studies, whereas the SCR method had poor reliability. Logan method, however, is a method simple to compute that shows accurate reproducibility with a reasonable level of inter- and intra-subject variability allowing crossover studies to follow-up the uptake of C-DTBZ in rat striatum.

Human embryonic stem cells-derived dopaminergic neurons transplanted in parkinsonian monkeys recover dopamine levels and motor behavior

“…To analyze the functional imaging outcome of cell transplantation, PET studies with a vesicular monoamine transporter probe were performed 9 months post-surgery. (+)-α-[ 11 C]dihydrotetrabenazine ( 11 C-DTBZ) was synthesized at the Unidad Radiofarmacia-Ciclotron of Universidad Nacional Autónoma de México, in the Tracerlab FXC-Pro synthesis module (GE Healthcare, Uppsala, Sweden) following published procedures 48 . For each animal, initial anesthesia was induced with Tiletamine/Zolazepam (125/125 mg) at a dose of 2 mg/kg (i.m.).…”

Human Embryonic Stem Cell-Derived Immature Midbrain Dopaminergic Neurons Transplanted in Parkinsonian Monkeys

“…PET probes for vesicular monoamine transporter 2 to analyze the functional imaging outcome of cell transplantation were performed 9 months post-surgery. The (+)-α-11Cdihydro tetrabenazine (11C-DTBZ) was synthesized at the Unidad Radiofarmacia-Ciclotrón of Universidad Nacional Autónoma de México in the Tracerlab FXC-Pro synthesis module (GE Healthcare, Uppsala, Sweden) following published procedures [74]. For each animal, initial anesthesia was induced with Tiletamine/Zolazepam (125/125 mg) at 2 mg/kg (i.m.).…”

Quantitative Rodent Brain Receptor Imaging

“…Hence, higher numbers of animals are needed to gain statistically reliable results. To assess the influence of these limitations on the estimation of quantitative binding values and to determine the optimal quantification approach for a given PET tracer in small laboratory animals, test-retest experiments have been performed for several CNS PET ligands [11][12][13][75][76][77][78][79][80][81][82][83]. In addition, physiological parameters can also vary within one animal at two different scan time points and may influence receptor availability, limiting the ability of PET to detect differences in an interventional study where a baseline and a treatment scan are compared.…”