3D Cell Culture System Could Revolutionize Cancer Diagnostics

New drugs and diagnostic methods should ideally be both safe and quickly accessible, but the preclinical testing phase often hinders rapid progress due to the high level of resources it requires. Particularly, the development of radioactive marker substances, known as "radiotracers," which are used to visualize physiological and pathological processes in the body, such as in cancer diagnostics, has traditionally involved time-consuming and costly tests, often relying on animal experimentation. These methods are not only ethically debated but also provide results that may not be applicable to humans. Now, researchers have developed an innovative bioanalytical testing system for radiopharmaceutical drug candidates for cancer diagnosis and therapy that eliminates the need for animal testing, allowing for faster, automated, and highly precise analyses.

The bioanalytical test system, developed by an interdisciplinary team including researchers from the University of Vienna (Vienna, Austria), uses human cells cultured on a silk matrix to test drug candidates under more realistic conditions—offering a faster and more accurate alternative to animal testing. The patented process combines chromatographic techniques (separation of substances based on interactions with a stationary and a mobile phase) with a dynamic 3D cell culture. The system uses biocompatible silk fibroin sponges as the stationary phase, serving as an artificial scaffold to immobilize human cells in a three-dimensional structure.

A specialized pump system continuously nourishes the cells, simulating human tissue conditions, while radiopharmaceutical agents are applied and observed in real-time using imaging technologies such as µPET/CT (positron emission tomography/computed tomography). This approach allows for a parallel evaluation of the binding properties of radiotracers and the biochemical processes within the cells. The new method, described in The Journal of Nuclear Medicine, enables the precise assessment of radioactive marker substances, including their binding properties, target accuracy, and potential side effects. Silk fibroin offers significant advantages due to its radiation stability and established use in cell culture. Additionally, the introduction of frits (sieve-like partitions) between the sponges reduces cell migration, enhancing the reproducibility of results. Key factors like radiation dose distribution and nutrient delivery to the cells can be carefully controlled.

Special emphasis was placed on automating and standardizing the processes to ensure the safe and efficient handling of radioactive substances. This method adheres to the 3R principle ("reduce, refine, replace") and aligns with the FDA's Critical Path Initiative. It has the potential to substantially reduce the need for animal testing, speed up the development of radiopharmaceuticals, and minimize radiation exposure for personnel. This innovative technology could establish new standards in preclinical radiopharmacy, promoting more sustainable and efficient drug development.

"With our method, we are not only creating an alternative to animal testing, but can also make the development of new radioactive marker substances much more efficient,” said first author Verena Pichler from the Department of Pharmaceutical Sciences at the University of Vienna. “Our aim is to raise diagnostics and therapy to a new level and improve ethical standards at the same time."

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