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“In Vivo Click PET Imaging Agents”: Improving clinical companion diagnostics

Project description

DEENESFRITPL

Advancing nuclear imaging

Nuclear imaging uses small amounts of radioactive substances to provide valuable information about the structure, function, and metabolism of various organs, assisting in the diagnosis and management of a wide range of diseases. However, the use of long-lived isotopes results in high radiation doses and restricts routine imaging procedures. To address this issue, the EU-funded Click-It project proposes a combinatorial approach that involves administration of a tagged nanomedicine followed by a radiolabelled probe, resulting in lower radiation doses and improved imaging contrast. The ultimate goal is to develop a clinically applicable nanomedicine-based imaging approach that can assist in disease diagnosis and management.

Objective

Companion diagnostics are crucial for drug development and disease management with regard to patient selection, therapy planning and monitoring. Nanomedicines such as antibodies have been proven to be optimal disease-targeting agents because they generally exhibit superior target uptake and retention. However, to date, nuclear imaging of nanomedicines has been limited to the use of long-lived isotopes to be compatible with the slow pharmacokinetics of these large molecules. Major drawbacks are high radiation doses, precluding routine and repeated companion imaging procedures.
The Click-It consortium aims to circumvent this issue by using pretargeting approach, which centers on the administration and target binding of a tagged nanomedicine followed by administration and binding of a small, fast-clearing, short-lived radiolabeled probe to the tag of the nanomedicine. This results in lower absorbed radiation doses and in a boost in target-blood ratios, which in turn leads to a superior imaging contrast. PET scan snapshots at multiple time-points provide long-term imaging information by applying short-lived nuclides. So far, only the fastest click reaction, the tetrazine ligation, has demonstrated potential in clinically relevant conditions. Recently, we have shown in a SPECT imaging study that this click reaction can be applied for non-internalizing nanomedicines in vivo.
This project aims at expanding the scope of click-pretargeted imaging to intracellular targets, because a majority of nanomedicines internalize and is thus not accessible with the current approach. Furthermore, we will expand our approach to short-lived, non-metal based, small molecule 18F-PET tracers, since PET offers a higher spatial and temporal resolution enabling quantitative decision making in disease diagnosis and management. Finally, the project aims to translate the developed click-pretargeting technology into a clinically applicable nanomedicine-based imaging approach in relevant patient-derived xenograft (PDX) mouse models.

Fields of science

Programme(s)

Topic(s)

Call for proposal

H2020-PHC-2014-2015

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Sub call

H2020-PHC-2015-two-stage

Funding Scheme

RIA - Research and Innovation action

Coordinator

REGION HOVEDSTADEN
Net EU contribution
€ 2 160 000,00
Address
KONGENS VAENGE 2
3400 Hillerod
Denmark

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Region
Danmark Hovedstaden Nordsjælland
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Links
Total cost
€ 2 160 000,00

Participants (5)

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Last update: 24 August 2022

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Permalink: https://cordis.europa.eu/project/id/668532

European Union, 2024