Projektbeschreibung
Fortschritte bei der nuklearen Bildgebung
Bei der nuklearen Bildgebung werden kleine Mengen radioaktiver Substanzen verwendet, um wertvolle Informationen über die Struktur, die Funktion und den Stoffwechsel verschiedener Organe zu erhalten, die bei der Diagnostik und der Behandlung einer Vielzahl von Krankheiten hilfreich sind. Die Verwendung langlebiger Isotope führt jedoch zu hohen Strahlendosen und schränkt die routinemäßigen Bildgebungsverfahren ein. Das Team des EU-finanzierten Projekts Click-It will dieses Problem lösen und schlägt dazu einen kombinatorischen Ansatz vor, der die Verabreichung eines markierten Nanomedikaments gefolgt von einer radioaktiv markierten Sonde vorsieht, was zu einer geringeren Strahlendosis und einem höheren Bildgebungskontrast führt. Endgültiges Ziel ist die Entwicklung eines klinisch anwendbaren, auf Nanomedizin basierenden Bildgebungsansatzes, der bei der Diagnostik und der Behandlung von Erkrankungen helfen kann.
Ziel
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.
Wissenschaftliches Gebiet
- 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
Programm/Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenUnterauftrag
H2020-PHC-2015-two-stage
Finanzierungsplan
RIA - Research and Innovation actionKoordinator
3400 Hillerod
Dänemark