Opis projektu
Rozwój techniki obrazowania jądrowego
Obrazowanie jądrowe wykorzystuje niewielkie ilości substancji radioaktywnych do badania struktury, funkcji i metabolizmu różnych narządów, dziki czemu pomaga w diagnozowaniu i leczeniu wielu różnych chorób. Jednak ponieważ stosuje się w nim izotopy długożyciowe, skutkuje ono wysokimi dawkami promieniowania, co ogranicza możliwości częstszego wykonywania procedur obrazowania. Aby rozwiązać ten problem, zespół finansowanego przez UE projektu Click-It proponuje podejście kombinatoryczne, które obejmuje podawanie znakowanego nanoleku, a następnie znakowanej radioaktywnie sondy, co pozwala na obniżenie dawek promieniowania i uzyskanie obrazu o wyższym kontraście. Prace te mają doprowadzić w dalszej perspektywie do opracowania opartego na nanomedycynie podejścia nadającego się do zastosowania w warunkach klinicznych, które może pomagać w diagnozowaniu i leczeniu chorób.
Cel
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.
Dziedzina nauki
- 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
Program(-y)
Zaproszenie do składania wniosków
Zobacz inne projekty w ramach tego zaproszeniaSzczegółowe działanie
H2020-PHC-2015-two-stage
System finansowania
RIA - Research and Innovation actionKoordynator
3400 Hillerod
Dania