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

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

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 canine patients.
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Coordinator

REGION HOVEDSTADEN

Address

Kongens Vaenge 2
3400 Hillerod

Denmark

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 160 000

Participants (5)

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KOBENHAVNS UNIVERSITET

Denmark

EU Contribution

€ 600 000

TECHNISCHE UNIVERSITAET WIEN

Austria

EU Contribution

€ 829 600

AIT AUSTRIAN INSTITUTE OF TECHNOLOGY GMBH

Austria

EU Contribution

€ 550 200

JOHANNES GUTENBERG-UNIVERSITAT MAINZ

Germany

EU Contribution

€ 300 000

TAGWORKS PHARMACEUTICALS BV

Netherlands

EU Contribution

€ 1 560 000

Project information

Grant agreement ID: 668532

Status

Ongoing project

  • Start date

    1 January 2016

  • End date

    31 December 2020

Funded under:

H2020-EU.3.1.

  • Overall budget:

    € 5 999 800

  • EU contribution

    € 5 999 800

Coordinated by:

REGION HOVEDSTADEN

Denmark