Descrizione del progetto
Progresso dell’imaging nucleare
L’imaging nucleare utilizza piccole quantità di sostanze radioattive per fornire informazioni preziose sulla struttura, la funzione e il metabolismo di vari organi, contribuendo alla diagnosi e alla gestione di un’ampia gamma di malattie. Tuttavia, l’uso di isotopi a lunga vita comporta alte dosi di radiazioni e limita le procedure di imaging di routine. Per risolvere questo problema, il progetto Click-It, finanziato dall’UE, propone un approccio combinatorio che prevede la somministrazione di una nanomedicina marcata seguita da una sonda radiomarcata, con conseguente riduzione delle dosi di radiazioni e miglioramento del contrasto di imaging. L’obiettivo finale è quello di sviluppare un approccio di imaging basato sulla nanomedicina, clinicamente applicabile, che possa aiutare nella diagnosi e nella gestione delle malattie.
Obiettivo
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.
Campo scientifico
- 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
Programma(i)
Argomento(i)
Invito a presentare proposte
Vedi altri progetti per questo bandoBando secondario
H2020-PHC-2015-two-stage
Meccanismo di finanziamento
RIA - Research and Innovation actionCoordinatore
3400 Hillerod
Danimarca