Dataset Information

Test-retest variability and reference region-based quantification of ¹⁸F-BCPP-EF for imaging mitochondrial complex I in the human brain.

ABSTRACT: Mitochondrial complex I (MC-I) is an essential regulator of brain bioenergetics and can be quantified in the brain using PET radioligand ¹⁸F-BCPP-EF. Here we evaluate the test-retest reproducibility of ¹⁸F-BCPP-EF in humans, and assess the use of a non-invasive quantification method (standardised uptake value ratio - SUVR). Thirty healthy volunteers had a 90-min dynamic ¹⁸F-BCPP-EF scan with arterial blood sampling, five of which received a second scan to be included in the test-retest analysis. Time-activity curves (TAC) were analysed using multilinear analysis 1 (MA1) and the two-tissue compartment model (2TC) to estimate volumes of distribution (V_T). Regional SUVR-1 values were calculated from the 70 to 90-min TAC data using the centrum semiovale as a pseudo reference region, and compared to kinetic analysis-derived outcome measures. The mean absolute test-retest variability of V_T ranged from 12% to 18% across regions. Both DVR-1and SUVR-1 had improved test-retest variability in the range 2%-7%. SUVR-1 was highly correlated with DVR-1 (r² = 0.97, n = 30). In conclusion, ¹⁸F-BCPP-EF has suitable test-retest reproducibility and can be used to quantify MC-I in clinical studies.

SUBMITTER: Mansur A

PROVIDER: S-EPMC7983506 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Test-retest variability and reference region-based quantification of 18F-BCPP-EF for imaging mitochondrial complex I in the human brain.

Mansur Ayla A Rabiner Eugenii A EA Tsukada Hideo H Comley Robert A RA Lewis Yvonne Y Huiban Mickael M Passchier Jan J Gunn Roger N RN

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20200605 4

Mitochondrial complex I (MC-I) is an essential regulator of brain bioenergetics and can be quantified in the brain using PET radioligand 18F-BCPP-EF. Here we evaluate the test-retest reproducibility of 18F-BCPP-EF in humans, and assess the use of a non-invasive quantification method (standardised uptake value ratio - SUVR). Thirty healthy volunteers had a 90-min dynamic 18F-BCPP-EF scan with arterial blood sampling, five of which received a second scan to be incl ...[more]

PMID: 32501157

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Project description:PurposeBeta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer's disease. [18F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [18F]PF-06684511 estimated in non-human primates was relatively high. This study was therefore designed to evaluate the whole-body distribution, dosimetry, quantification, and test-retest reliability of imaging brain BACE1 with [18F]PF-06684511 in healthy volunteers.MethodsFive subjects were studied for the dosimetry study. Whole-body PET was performed for 366 min with 4 PET-CT sessions. Estimates of the absorbed radiation dose were calculated using the male adult model. Eight subjects participated in the test-retest study. Brain PET measurements were conducted for 123 min with an interval of 5 to 19 days between test and retest conditions. The total distribution volume (VT) was estimated with one-tissue (1T), two-tissue (2T), compartment model (CM), and graphical analysis. Test-retest variability (TRV) and intraclass correlation coefficient (ICC) of VT were calculated as reliability measures.ResultsIn the dosimetry study, the highest uptake was found in the liver (25.2 ± 2.3 %ID at 0.5 h) and the largest dose was observed in the pancreas (92.9 ± 52.2 μSv/MBq). The calculated ED was 24.7 ± 0.8 μSv/MBq. In the test-retest study, 2TCM described the time-activity curves well. VT (2TCM) was the highest in the anterior cingulate cortex (6.28 ± 1.09 and 6.85 ± 0.81) and the lowest in the cerebellum (4.23 ± 0.88 and 4.20 ± 0.75). Mean TRV and ICC of VT (2TCM) were 16.5% (12.4-20.5%) and 0.496 (0.291-0.644).ConclusionThe ED of [18F]PF-06684511 was similar to other 18F radioligands, allowing repeated PET measurements. 2TCM was the most appropriate quantification method. TRV of VT was similar to other radioligands without a reference region, albeit with lower ICC. These data indicated that [18F]PF-06684511 is a suitable radioligand to measure BACE1 level in the human brain.Trial registrationEudraCT 2016-001110-19 (registered 2016-08-08).

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Dataset Information

Test-retest variability and reference region-based quantification of ¹⁸F-BCPP-EF for imaging mitochondrial complex I in the human brain.

Publications

Test-retest variability and reference region-based quantification of <sup>18</sup>F-BCPP-EF for imaging mitochondrial complex I in the human brain.

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