MICA: [18F]LW223: a superior TSPO PET radiotracer for a clinical breakthrough to detect regional tissue inflammation

This project will study the utility of a new tool for scanning patients that will allow doctors to better understand how diseases start and evolve as well as how to better treat their patients. This new tool is based on a highly specialized scanning technique called positron emission tomography or PET. This technique allows for the study of different processes happening inside the human body by injecting a small amount of a substance into patients. That substance is called a radiotracer and after injection it travels in the patients' blood stream, reaches the target inside the body and emits a signal that can be detected outside the patients' body using a very sensitive camera. Our new radiotracer, that we named LW223, was designed so it can target inflammation inside the body. In this project we will be tracking LW223 signal inside the human body over time. We will do those tracking studies both in healthy conditions and post-heart attack to confirm this signal represents tissue inflammation.

Inflammation plays a critical role in the development, progression and clinical outcomes for a number of human diseases, including highly prevalent cardiovascular, neurological and oncological diseases. Despite this central role, clinical biomarkers for quantification of regional tissue inflammation in vivo and non-invasively with high sensitivity and specificity are not available. In this project, we propose to address this clinical need by developing a new imaging biomarker with potential to transform clinical diagnosis, management of a plethora of human diseases, drug development and treatment of multiple diseases. Our new imaging biomarker targets the 18kDa translocator protein (TSPO), a biological target abundantly proven to measure inflammation in pathologies throughout the body, and makes use of Positron Emission Tomography (PET) technology as an approach to achieve greatest sensitivity and specificity for detection of inflammation. Our new imaging biomarker, [18F]LW223, aims to address bottlenecks associated with current and long-standing TSPO PET technology: (1) the inability to scan the whole-human population due to sensitivity toward the rs6971 genetic polymorphism; (2) the lack of clinical universalism due to complex imaging protocols that are only possible in a limited number of highly specialised PET centres worldwide; and (3) the difficult market commercialisation due to labelling with short-lived radioisotopes. This project will conduct first in human studies with [18F]LW223 and will explore its utility as a biomarker of regional tissue inflammation in humans versus other clinically used metrics in the national health service. If successful, results from this study will catapult the use of quantitative TSPO PET in many diseases in humans and model organisms worldwide.