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Dye tests on organoids to enhance surgical precision

Researchers at the Princess Máxima Center have developed an advanced system to test dyes for fluorescence-guided surgery. This new system uses organoids: miniature versions of human organs or tumors grown in the lab. The goal is to make tumor tissue more visible during surgery, allowing surgeons to work more precisely and damage as little healthy tissue as possible. 

Fluorescence-guided surgery is a technique where a special dye makes tumors visible during surgery. This helps surgeons clearly see where the tumor ends and healthy tissue begins, enabling complete removal of the tumor without harming too much healthy tissue. 

Finding the right dyes to color the tumor is a long and complex process. Traditionally, these dyes are tested one by one in animal models, but this does not always give the best results. Moreover, fluorescence techniques are not very specific for tumors, as the dye sometimes marks healthy tissue as well. 

Organoids as an accurate test model 
Researchers from the Rios group at the Princess Máxima Center have developed a new system using organoids. These are miniature versions of human organs grown in the lab, accurately mimicking the properties of both healthy tissues and tumors. 

Dr. Ravian van Ineveld, a postdoc in the Rios group and manager of the Imaging Center, explains: ‘With organoids, we can more accurately assess how well a dye binds to tumor tissue. For example, we check if the dye binds to breast cancer organoids and not to healthy breast tissue organoids.’ 

Results and clinical benefits 
The researchers, with Bernadette Jeremiasse as first author, published their results in the scientific journal EMBO Molecular Medicine. They successfully tested the new system in neuroblastoma and breast cancer. Using organoids allows for faster and more efficient testing of different dyes. Organoids better mimic the human properties of both healthy tissues and tumors, leading to more representative results than animal testing. 

The platform is useful for both childhood and adult cancers. It is expected that these improvements can lead to more precise surgeries, fewer complications, and better survival rates for patients in the future. 

Image by Ravian van Ineveld, The Dream3DLab, Princess Máxima Center and Oncode Institute. 

Advanced techniques for dye screening 
‘Multispectral 3D imaging is a technique where images are made with different colors of light, allowing you to see multiple dyes at once,’ explains Ravian van Ineveld. ‘This makes testing much faster and results more accurate.’ 

He elaborates: ‘In multispectral microscopy, we test twice as many fluorescent dyes and multiple dyes simultaneously. This not only speeds up the process but also provides insight into using different dye combinations.’ 

Prof. Dr. Marc Wijnen, a pediatric surgeon and professor of pediatric oncological surgery, explains: ‘With this technique, we can quickly develop a dye specific to the tumor or patient. This means we can create and use a unique fluorescent dye for each child with cancer during surgery.’ 

Future perspectives 
Ravian van Ineveld looks to the future: ‘We expect our new system to be a quick and accurate addition to existing processes for finding new dyes. The system can also be used for other applications where tissue markers are studied, such as in immunotherapy and targeted therapy. With this, we hope to make a significant step forward in treating children with cancer.