Could novel radiopharmaceuticals for PET imaging improve the way we diagnose Alzheimer’s?

Written by Alice Bough, Future Science Group

A team of researchers from John Hopkins University (MD, USA) have evaluated the tau-specific binding abilities of three different radiopharmaceuticals and their potential to be used in PET imaging of tau proteins. The paper, which has been published in the Journal of Nuclear Medicine, identified radiotracers that have the potential to be utilized in a clinical setting for the diagnosis of Alzheimer’s disease (AD).
Tau tangles in the brain are one of the markers of AD and may be utilized as a therapeutic target for the treatment of this form of dementia.

The ability to determine tau density and distribution could be a way of diagnosing and monitoring the progression of AD. This study has identified a promising PET tracer for imaging and measuring the pathology of tau. “We compared three novel tau-specific radiopharmaceuticals – 11C-RO-963, 11C-RO-643, and 18F-RO-948 – that showed pre-clinical in vitro and in vivo promise for use in imaging human tau,” stated lead author on the paper, Dean Wong (John Hopkins University).

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People with AD and healthy individuals received two different tau tracers. Following administration of the tracers, PET scans were performed on the subjects’ brains. In all subjects, the trend was for 18F-RO-948 to have the highest standardized uptake value. “This design allowed us to select one radioligand, 18F-R0-948, as the most promising second-generation tau radiopharmaceutical for larger scale use in human PET tau imaging,” commented Wong.

Following the identification of 18F-RO-948 as the radiopharmaceutical with the most potential for tau-specific imaging, the study focused on analyzing the kinetic properties and binding specificity of the radioligand.

“Importantly, this new tracer appears to have much less off-target binding than was reported for existing tau tracers,” explained Wong. “Especially, it has less binding to the choroid plexus adjacent to the hippocampus, which has confounded interpretation of mesial temporal tau measured by first-generation PET tau tracers.”

Not only do these novel radiotracers show potential to be utilized for Alzheimer’s diagnosis, they may also improve analysis of Alzheimer’s treatment methods. “Better tau PET radiopharmaceuticals also provide the promise of improved target engagement and monitoring of anti-tau treatments in future Alzheimer’s clinical trials,” concluded Wong.

Sources: Wong DF, Comley RA, Kuwabara H et al. Characterization of 3 novel tau radiopharmaceuticals, 11C-RO-963, 11C-RO-643, and 18F-RO-948, in healthy controls and in Alzheimer subjects. J. Nucl. Med. 59(12), 1869–1876 (2018); www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=30455