The design and preclinical evaluation of a single-label bimodal nanobody tracer for image-guided surgery

Intraoperative guidance using targeted fluorescent tracers can potentially provide surgeons with real-time feedback on the presence of tumor tissue in resection margins. To overcome the limited depth penetration of fluorescent light, combining fluorescence with SPECT/CT imaging and/or gamma-ray tracing has been proposed. Here, we describe the design and preclinical validation of a novel bimodal nanobody-tracer, labeled using a "multifunctional single attachment point" (MSAP) label, integrating a Cy5 fluorophore and a diethylenetriaminepentaacetic acid (DTPA) chelator into a single structure. After conjugation of the bimodal MSAP to primary amines of the anti-HER2 nanobody 2Rs15d and In-111-labeling of DTPA, the tracer's characteristics were evaluated in vitro. Subsequently, its biodistribution and tumor targeting were assessed by SPECT/CT and fluorescence imaging over 24 h. Finally, the tracer's ability to identify small, disseminated tumor lesions was investigated in mice bearing HER2-overexpressing SKOV3.IP1 peritoneal lesions. [In-111]In-MSAP.2Rs15d retained its affinity following conjugation and remained stable for 24 h. In vivo SPECT/CT and fluorescence images showed specific uptake in HER2-overexpressing tumors with low background. High tumor-to-muscle ratios were obtained at 1h p.i. and remained 19-fold on SPECT/CT and 3-fold on fluorescence images over 24 h. In the intraperitoneally disseminated model, the tracer allowed detection of larger lesions via nuclear imaging, while fluorescence enabled accurate removal of submillimeter lesions. Bimodal nuclear/fluorescent nanobody-tracers can thus be conveniently designed by conjugation of a single-molecule MSAP-reagent carrying a fluorophore and chelator for radioactive labeling. Such tracers hold promise for clinical applications.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Estudio comparativo entre la reglamentación española y belga en el campo del rendimiento energético de los edificios

[EN] This bachelor thesis will explain how it is possible and which factors are important to obtain buildings which apply for certificates such as passive or active buildings. These buildings belong to a group of buildings called nearly zero energy buildings. This will be done for Spain and Belgium. The main influences such as the climate differences will be explained because they have a significant influence on the building performances. At the end, the way we calculate the energy performances of buildings will be explaine.[ES] Esta tesis de licenciatura explicará cómo es posible y qué factores son importantes para obtener edificios que soliciten certificados como edificios pasivos o activos. Estos edificios pertenecen a un grupo de edificios llamados edificios de energía casi nula. Esto se hará para España y Bélgica. Las principales influencias tales como las diferencias climáticas se explicarán ya que tienen una influencia significativa en las actuaciones del edificio. Al final, se explicará la forma en que calculamos el rendimiento energético de los edificiosDe Sloovere, MKD. (2019). Comparison between Spain and Belgium in the field of energy performance and passive buildings regulations. http://hdl.handle.net/10251/124355TFG