Descripción del proyecto
Avances en gammagrafía
La gammagrafía utiliza pequeñas cantidades de sustancias radiactivas para proporcionar información valiosa sobre la estructura, función y metabolismo de diversos órganos, lo que ayuda en el diagnóstico y tratamiento de una amplia gama de enfermedades. Sin embargo, el uso de isótopos de vida larga da lugar a altas dosis de radiación y restringe los procedimientos rutinarios de obtención de imágenes. Para resolver este problema, el equipo del proyecto Click-It, financiado con fondos europeos, propone un método combinatorio que implica la administración de un nanofármaco marcado seguida de una sonda radiomarcada, con lo que se reducen las dosis de radiación y se mejora el contraste de las imágenes. El objetivo final es desarrollar un método de obtención de imágenes basado en nanofármacos que sea clínicamente aplicable y pueda ayudar en el diagnóstico y tratamiento de enfermedades.
Objetivo
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.
Ámbito científico
- 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
Programa(s)
Convocatoria de propuestas
Consulte otros proyectos de esta convocatoriaConvocatoria de subcontratación
H2020-PHC-2015-two-stage
Régimen de financiación
RIA - Research and Innovation actionCoordinador
3400 Hillerod
Dinamarca