Lantheus Announces Collaboration With NIH to Study Tau Imaging Agent in Alzheimer Disease

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The CLARiTI study spans across all 37 Alzheimer Disease Research Centers, collecting evidence on imaging and blood-based biomarkers to generate etiologic patient profiles of mixed dementia.

Sterling Johnson, PhD, professor of medicine at the University of Wisconsin School of Medicine

Sterling Johnson, PhD

According to a recent announcement, Lantheus, a radiopharmaceutical-focused company, will be collaborating with the National Institute of Health (NIH) on a new study to test its PET tau imaging agent, MK-6260, in the investigation of Alzheimer disease (AD) and related dementias. Otherwise known as the CLARiTI (Consortium for Clarity in ADRD Research Through Imaging) study, this multi-site, 5-year trial will enroll 2000 individuals across the US.1

Tau PET has shown to have great potential in contributing to the accurate diagnosis of AD, adding to the ability to stage disease beyond amyloid PET. MK-6240, a clinical-stage F18-labeled PET imaging technique, targets aggregated tau protein in the form of neurofibrillary tangles (NFTs), which are considered a hallmark of several neurodegenerative diseases, including AD. CLARiTI is expected to span across all 37 AD Research Centers (ADRCs) in the US and is designed to collect data on imaging and blood-based biomarkers to generate etiologic profiles for cased of mixed dementia.

"This study is designed to shed light on the complex interplay of multiple pathologies contributing to dementia, ultimately advancing our understanding and treatment of this devastating condition," study lead Sterling Johnson, PhD, professor of medicine at the University of Wisconsin School of Medicine, said in a statement.1 "We are thrilled to partner with Lantheus to use MK-6240 for tau PET imaging in this important study."

CLARiTI will utilize the National Alzheimer’s Coordinating Center (NACC) infrastructure to accelerate and track MRI and PET image submissions from the ADRCs and to make additional image and summary results available to AD/ADRD researchers through the NACC Data Front Door. There are several different core aspects to the study, including a neuropathological core and digital pathology resource that facilitates neuropath-guided image analysis. The intent is that this will be leveraged to enhance the existing NIH investment in the program.

Other core aspects of CLARiTI include providing resources related to the recruitment of underrepresented individuals, as well as providing workflows for disclosure of PET status to individual sites, which may be helpful for sites that do not yet have workflows in place. Additionally, CLARiTI will build a bridge to future uniform plasma ADRD biomarker characterization in the ADRCs.

"MK-6240 is poised to play a pivotal role in propelling Alzheimer’s diagnosis and treatment research to new heights," Jean-Claude Provost, MD, chief medical officer at Lantheus, said in a statement.1 "This agreement aligns with Lantheus’ purpose to actively cultivate collaborations that empower researchers worldwide with essential tools to accelerate clinical research and development of therapies. In an era defined by an unprecedented number of Alzheimer’s diagnoses, the CLARiTI study represents a significant milestone in Alzheimer’s research, with the potential to change the trajectory of this degenerative disease."

MK-6240 first demonstrated its promise as a PET tracer in a preclinical model published in 2016. In vitro blinding studies were conducted with H-MK-6240 in tissue slices and homogenates from cognitively normal and AD human brain donors to evaluate tracer affinity and selectivity for NFTs. All told, the H-MK-6240 binding pattern was shown to be consistent with the distribution of phosphorylated tau in human AD brain slices.2

Additional data from the analysis showed that H-MK-6240 bound with high affinity to human AD brain cortex homogenates containing abundant NFTs but bound poorly to amyloid plaque-rich, NFT-poor AD brain homogenates. The tau tracer demonstrated no displaceable binding in the subcortical regions of human AD brain slices and in the hippocampus entorhinal cortex of non-AD human brain homogenates. Furthermore, in monkey PET studies, 18F-MK-6240 displayed rapid and homogenous distribution in the brain.

Previous research has shown that tau PET can be also useful in non-AD tauopathies, most notably frontotemporal lobar degeneration, which encompasses a group of heterogenous neurodegenerative disorders typically demonstrating frontal and/or temporal cortical atrophy. Specifically, it has demonstrated a role in diagnosing disorders like progressive supranuclear palsy and CBS. Overall, many in the field believe tau PET provides additive value to the current and future disease-modifying therapies for AD.3

REFERENCES
1. Latheus announces collaboration to provide novel tau imaging agent for large consortium clinical trial sponsored by the National Institute on Aging. News release. Lantheus. February 13, 2024. Accessed March 15, 2024. https://finance.yahoo.com/news/lantheus-announces-collaboration-novel-tau-133000553.html
2. Hostetler ED, Walji AM, Zeng Z, et al. Preclinical characterization of 18F-MK-6240, a promising PET tracer for in vivo quantification of human neurofibrillary tangles. Journ of Nuclear Med. 2016;57(10);1599-1606. doi:10.2967/jnumed.115.171678.
3. Petersen GC, Roytman M, Chiang G, Li Y, Gordon ML, Franceschi AM. Overview of tau PET molecular imaging. Curr Opin Neurol. 2022;35(2):230-239. doi:10.1097/WCO.0000000000001035
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