# Translation of tau-selective PET radiopharmaceuticals in Alzheimers patients

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $724,475

## Abstract

ABSTRACT
This is the first resubmission of a methodology oriented R01 grant application. The public health burden of
Alzheimer's disease (AD) is increasing with devastating projections on an international basis. Although much
knowledge has been gained recently about the AD disease process, as a result of amyloid-β (Aβ) positron-
emission tomography (PET) imaging in combination with MRI hippocampal volume, FDG PET, amyloid and tau
cerebrospinal fluid concentrations and cognitive performance - there is still much to be understood, particularly
as the field moves further from end-stage disease to preclinical AD. A decade ago, AD clinical research was
transformed when it became possible to specifically detect in vivo one of the defining pathologic changes of
AD, Aβ plaques using PET. However, amyloid deposition is not itself robustly associated with clinical status,
cognitive performance, or stage of progression. In contrast, the pattern of tau pathology, the other AD-defining
lesion, is more closely related to the AD phenotype than Aβ pathology. A first generation tau-PET radiotracer,
[18F]T807 (a.k.a. [18F]AV-1451; Flortaucipir), emerged as a promising tool for human tau imaging and is the
most widely used to date, with pioneering studies originating from our laboratories at the Massachusetts
General Hospital. There remains a critical need to improve tau-PET tracers in 3 areas in order to improve early
disease detection and enable multiple longitudinal follow-ups required for disease-modifying therapeutic trials:
1) reduction of off-target binding in, for example, structures adjacent to hippocampus; 2) improved in vivo
kinetics to ensure stable quantification of tau load across low-to-high binders; and 3) greater signal-to-noise at
the pre-symptomatic end of the AD spectrum. We have recently co-developed a novel second generation tau-
PET tracer, [18F]MK-6240, in collaboration with Merck Research Laboratories. The overall goal is to
comprehensively evaluate [18F]MK-6240, using a longitudinal study design to show improved quantification of
tau load throughout brain. Our study will address remaining key obstacles needed to ensure successful
application of [18F]MK-6240 for clinical research investigations of AD. Specifically our aims are: A) To perform
a fully quantitative arterial-based kinetic evaluation of [18F]MK-6240 kinetics; B) To measure the distribution of
[18F]MK-6240 in brain, at baseline and at 1-year (yr) follow-up; C) To develop a high yield radiosynthesis of
[18F]MK-6240 using our advanced radiofluorination technology thereby facilitating widespread distribution and
multi-center trials; and D) and exploratory aim to examine region- and substrate-specific autoradiographic
binding of [18F]MK-6240 and its off-target binding to other amyloid and non-amyloid proteins. The rigorous
evaluation of this novel, highly specific tau-PET tracer with greater sensitivity for in vivo measurement of tau
pathology and monitoring of disease staging is cri...

## Key facts

- **NIH application ID:** 9936414
- **Project number:** 5R01AG052414-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Julie C Price
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $724,475
- **Award type:** 5
- **Project period:** 2018-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936414

## Citation

> US National Institutes of Health, RePORTER application 9936414, Translation of tau-selective PET radiopharmaceuticals in Alzheimers patients (5R01AG052414-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9936414. Licensed CC0.

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