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

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.