Description du projet
Faire progresser l’imagerie nucléaire
L’imagerie nucléaire utilise de petites quantités de substances radioactives pour fournir des informations précieuses sur la structure, la fonction et le métabolisme de divers organes, contribuant au diagnostic et à la gestion d’un large éventail de maladies. Cependant, l’utilisation d’isotopes à longue durée de vie expose le patient à des doses de radiation élevées, ce qui limite les procédures d’imagerie de routine. Pour pallier à ce problème, le projet Click-It, financé par l’UE, propose une approche combinée qui implique l’administration d’un nanomédicament marqué suivit d’une sonde radiomarquée, ce qui permet de réduire les doses d’irradiation et d’améliorer le contraste de l’imagerie. L’objectif ultime du projet est de développer une approche d’imagerie basée sur la nanomédecine et cliniquement applicable, qui puisse contribuer au diagnostic et à la gestion de la maladie.
Objectif
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.
Champ scientifique
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health sciencesclinical medicineradiologynuclear medicine
- medical and health sciencesmedical biotechnologynanomedicine
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmacokinetics
Programme(s)
Régime de financement
RIA - Research and Innovation actionCoordinateur
3400 Hillerod
Danemark