[18F]THK-5117 and [18F]THK-5317
[18F]THK-5117 is a racemic tracer. Enantiomerically pure (S)-[18F]THK-5117 ([18F]THK-5317) can be used instead of the racemic mixture if absolute quantification is required, because any differences in metabolism and kinetics between the S- and R-enantiomers would complicate the analysis (Jonasson et al., 2016).
Test-retest variability for [18F]THK-5317 is very low (Chiotis et al., 2016). [18F]THK-5117/[18F]THK-5317 PET studies have shown good visual separation of healthy subjects and Alzheimer's disease (AD) patients, with high uptake in brain areas known to have high tau protein content in AD, and different uptake pattern than when using β-amyloid tracer [11C]PIB or FDG (Okamura et al., 2014; Harada et al., 2015; Chiotis et al., 2016). However, in vivo [18F]THK5317 uptake in the human brain did not correlate with biopsy verified tau pathology (Leinonen et al., 2018). Like most tau radioligands, [18F]THK5317 is bound to MAO-B (Murugan et al., 2019). In mouse model of AD, [18F]THK5317 brain uptake is associated with Aβ plaques and MAO-B, but not with hyper-phosphorylated tau (Alzghool et al., 2021).
Harada et al. (2015) performed a 90-min PET scan, and calculated the uptake ratios of regions-of-interest and cerebellar cortex. In vivo [18F]THK5117 ROI/cerebellum ratio (60-90 min) in the human brain did not correlate with biopsy verified tau pathology (Leinonen et al., 2018). Jonasson et al. (2016) computed BPND for (S)-[18F]THK-5117 using plasma-input Logan plot, reference-input Logan plot, and SRTM, with cerebellum gray matter as reference region; VOI-based analysis provided robust results with all methods for scan durations of 60 min, and reference-input Logan performed best in computation of parametric images.
Alzghool OM, Rokka J, López-Picón FR, Snellman A, Helin JS, Okamura N, Solin O, Rinne JO, Haaparanta-Solin M. (S)-[18F]THK5117 brain uptake is associated with Aβ plaques and MAO-B enzyme in a mouse model of Alzheimer's disease. Neuropharmacology 2021; 196: 108676. doi: 10.1016/j.neuropharm.2021.108676.
Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N, Hiraoka K, Watanuki S, Shidahara M, Miyake M, Ishikawa Y, Matsuda R, Inami A, Yoshikawa T, Tago T, Funaki Y, Iwata R, Tashiro M, Yanai K, Arai H, Kudo Y. [18F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease. Eur J Nucl Med Mol Imaging 2015; 42(7): 1052-1061. doi: 10.1007/s00259-015-3035-4.
Jonasson M, Wall A, Chiotis K, Saint-Aubert L, Wilking H, Sprycha M, Borg B, Thibblin A, Eriksson J, Sörensen J, Antoni G, Nordberg A, Lubberink M. Tracer kinetic analysis of (S)-18F-THK5117 as a PET tracer for assessing tau pathology. J Nucl Med. 2016; 57(4): 574-581. doi: 10.2967/jnumed.115.158519.
Lemoine L, Saint-Aubert L, Marutle A, Antoni G, Eriksson JP, Ghetti B, Okamura N, Nennesmo I, Gillberg PG, Nordberg A. Visualization of regional tau deposits using 3H-THK5117 in Alzheimer brain tissue. Acta Neuropathol Commun. 2015; 3:40. doi: 10.1186/s40478-015-0220-4.
Okamura N, Furumoto S, Harada R, Tago T, Yoshikawa T, Fodero-Tavoletti M, Mulligan RS, Villemagne VL, Akatsu H, Yamamoto T, Arai H, Iwata R, Yanai K, Kudo Y. Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. J Nucl Med. 2013; 54(8): 1420-1427. doi: 10.2967/jnumed.112.117341.
Okamura N, Harada R, Furumoto S, Furukawa K, Ishiki A, Tomita N, Tashiro M, Iwata R, Yanai K, Arai H, Kudo Y. Comparison of 18F-THK5117 and 11C-PIB PET images in patients with Alzheimer's disease. Alzheimer's Dementia 2014; 10(4): P116. doi: 10.1016/j.jalz.2014.05.223.
Villemagne VL, Fodero-Tavoletti MT, Masters CL, Rowe CC. Tau imaging: early progress and future directions. Lancet Neurol. 2015; 14: 114-124. doi: 10.1016/S1474-4422(14)70252-2.
Tags: Tau protein
Updated at: 2022-01-24
Created at: 2015-08-23
Written by: Vesa Oikonen