Dataset Information

Measuring cerebral perfusion with [¹¹C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline.

ABSTRACT: Positron emission tomography imaging of glucose hypometabolism and amyloid deposition are two well-established methods to evaluate preclinical changes in Alzheimer's disease and people with Down syndrome. However, the use of both imaging modalities may overburden participants, particularly those with intellectual disabilities and cognitive impairment. The relative tracer delivery of the [¹¹C]-Pittsburgh Compound B has been proposed as a viable surrogate for cerebral perfusion. Here, we studied the impact of amyloid pathology on perfusion changes in Down syndrome and evaluated its associations with cognitive impairment. In total, 47 adults with Down syndrome underwent the [¹¹C]-Pittsburgh Compound B imaging and structural imaging. The structural data were processed with Freesurfer to obtain anatomical segmentations and cortical thickness. The relative tracer delivery from [¹¹C]-Pittsburgh Compound B was derived using a simplified reference tissue model. The sample was stratified into those with minimal amyloid burden (n?=?25) and those with elevated amyloid (n?=?22). We found significant and widespread reductions of cerebral perfusion in those with elevated amyloid burden, independent of age, gender, cognitive function and cortical thickness. In addition, cerebral perfusion was associated with the cognitive impairment among the Down syndrome group with elevated amyloid burden. These findings highlight the promising utility of the relative tracer delivery of the [¹¹C]-Pittsburgh Compound B as a surrogate index in clinical trials for monitoring disease progression or tracking physiologic changes over time in Down syndrome.

SUBMITTER: Mak E

PROVIDER: S-EPMC7849981 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Measuring cerebral perfusion with [<sup>11</sup>C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline.

Mak Elijah E Grigorova Monika M Beresford-Webb Jessica J Malpetti Maura M Walpert Madeline M Brown Stephanie S Jones Elizabeth E Clare Isabel I Hong Young T YT Fryer Tim D TD Coles Jonathan P JP Aigbirhio Franklin I FI Menon David K DK Nestor Peter J PJ Holland Anthony J AJ Zaman Shahid H SH

Brain communications 20201118 1

Positron emission tomography imaging of glucose hypometabolism and amyloid deposition are two well-established methods to evaluate preclinical changes in Alzheimer's disease and people with Down syndrome. However, the use of both imaging modalities may overburden participants, particularly those with intellectual disabilities and cognitive impairment. The relative tracer delivery of the [<sup>11</sup>C]-Pittsburgh Compound B has been proposed as a viable surrogate for cerebral perfusion. Here, w ...[more]

PMID: 33543138

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Project description:BackgroundThe standard reference region (RR) for amyloid-beta (Aβ) PET studies is the cerebellar grey matter (GMCB), while alternative RRs have mostly been utilized without prior validation against the gold standard. This study compared five commonly used RRs to gold standard plasma input-based quantification using the GMCB.MethodsThirteen subjects from a test-retest (TRT) study and 30 from a longitudinal study were retrospectively included (total: 17 Alzheimer's disease, 13 mild cognitive impairment, 13 controls). Dynamic [11C]PiB PET (90 min) and T1-weighted MR scans were co-registered and time-activity curves were extracted for cortical target regions and the following RRs: GMCB, whole cerebellum (WCB), white matter brainstem/pons (WMBS), whole brainstem (WBS) and eroded subcortical white matter (WMES). A two-tissue reversible plasma input model (2T4k_Vb) with GMCB as RR, reference Logan and the simplified reference tissue model were used to derive distribution volume ratios (DVRs), and standardized uptake value (SUV) ratios were calculated for 40-60 min and 60-90 min intervals. Parameter variability was evaluated using TRT scans, and correlations and agreements with the gold standard (DVR from 2T4k_Vb with GMCB RR) were also assessed. Next, longitudinal changes in SUVs (both intervals) were assessed for each RR. Finally, the ability to discriminate between visually Aβ positive and Aβ negative scans was assessed.ResultsAll RRs yielded stable TRT performance (max 5.1% variability), with WCB consistently showing lower variability. All approaches were able to discriminate between Aβ positive and Aβ negative scans, with highest effect sizes obtained for GMCB (range - 0.9 to - 0.7), followed by WCB (range - 0.8 to - 0.6). Furthermore, all approaches provided good correlations with the gold standard (r ≥ 0.78), while the highest bias (as assessed by the regression slope) was observed using WMES (range slope 0.52-0.67), followed by WBS (range slope 0.58-0.92) and WMBS (range slope 0.62-0.91). Finally, RR SUVs were stable across a period of 2.6 years for all except WBS and WMBS RRs (60-90 min interval).ConclusionsGMCB and WCB are considered the best RRs for quantifying amyloid burden using [11C]PiB PET.

Project description:BackgroundThe ?-amyloid radiotracer [11C] PiB is extensively used for the Positron Emission Tomography (PET) diagnosis of Alzheimer's Disease and related dementias. For clinical use, [11C] PiB is produced using the 11C-methylation method ([11C] Methyl iodide or [11C] methyl triflate as 11C-methylation agents), which represents the most employed 11C-labelling strategy for the synthesis of 11C-radiopharmaceuticals. Recently, the use of direct [11C]CO2 fixation for the syntheses of 11C-tracers has gained interest in the radiochemical community due to its importance in terms of radiochemical versatility and for permitting the direct employment of the cyclotron-produced precursor [11C]CO2. This paper presents an optimised alternative one-pot methodology of [11C]CO2 fixation-reduction for the rapid synthesis of [11C] PiB using an automated commercial platform and its quality control.Results[11C] PiB was obtained from a (25.9?±?13.2)% (Average?±?Variation Coefficient, n?=?3) (end of synthesis, decay corrected) radiochemical yield from trapped [11C]CO2 after 1?min of labelling time using PhSiH3 / TBAF as the fixation-reduction system in Diglyme at 150?°C. The radiochemical purity was higher than 95% in all cases, and the molar activity was (61.4?±?1.6) GBq/?mol. The radiochemical yield and activity (EOS) of formulated [11C] PiB from cyclotron-produced [11C]CO2 was (14.8?±?12.1)%, decay corrected) and 9.88?GBq (± 6.0%), respectively. These are higher values compared to that of the 11C-methylation method with [11C]CH3OTf (~?8.3%).ConclusionsThe viability of the system PhSiH3 / TBAF to efficiently promote the radiosynthesis of [11C] PiB via direct [11C]CO2 fixation-reduction has been demonstrated. [11C] PiB was obtained through a fully automated radiosynthesis with a satisfactory yield, purity and molar activity. According to the results, the one-pot methodology employed could reliably yield sufficiently high tracer amounts for preclinical and clinical use.

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Measuring cerebral perfusion with [¹¹C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline.

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Measuring cerebral perfusion with [<sup>11</sup>C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline.

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Measuring cerebral perfusion with [11C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline.

Publications

Measuring cerebral perfusion with [<sup>11</sup>C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Measuring cerebral perfusion with [¹¹C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline.