A new nuclear medicine imaging method could help diagnose widespread tumours, such as breast, colon, pancreas, lung and head and neck cancer better than current methods, with less inconvenience to patients and with equal or improved accuracy, according to researchers from the University Hospital of Heidelberg and at the German Cancer Research Center. The paper, ‘A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts’, was published in Journal of Nuclear Medicine
The new imaging method, developed by a team of German researchers, targets cancer-associated fibroblasts, a subpopulation of tumour stroma cells (connective tissue cells). These fibroblasts are an attractive target for diagnostic imaging and therapy, as they are present in more than 90 percent of epithelial carcinomas, including pancreatic, colon and breast cancer.
Cancer-associated fibroblasts (CAFs) have a high expression of fibroblast activation protein (FAP) and are known to be involved in tumour growth, migration and progression. They are also genetically more stable than cancer cells, making them less susceptible to developing therapy resistance.
"The appearance of FAP in CAFs in many epithelial tumours and the fact that overexpression is associated with a worse prognosis led to the hypothesis that FAP activity is involved in cancer development, as well as in cancer cell migration and spread," said Dr Uwe Haberkorn, professor of nuclear medicine at the University Hospital of Heidelberg and at the German Cancer Research Center. "Therefore, the targeting of this enzyme for imaging and endo-radiotherapy can be considered as a promising strategy for the detection and treatment of malignant tumours."
Based on an FAP-specific enzyme inhibitor (FAPI), the team developed the positron emission tomography (PET) tracer gallium-68 (68Ga)-labelled FAPI, which was tested first on mouse models then through proof-of-concept PET/CT imaging of three patients. The results showed high tracer uptake by the tumours and fast body clearance, resulting in high-contrast images and very low binding to healthy tissue in both animals and tumour patients.
"A comparison to fluorodeoxyglucose [18F-FDG] - the common standard in tumour imaging - revealed a clear advantage of our tracer with regard to tumour uptake and image contrast in many tumours,” explained Professor Haberkorn.
The fact that radiolabelled FAPIs allow fast imaging with very high contrast in tumours that have a high stromal content makes them versatile, pan-tumour agents. These molecules can be coupled to DOTA or other chelators, allowing labelling not only with 68Ga, but also with therapeutic isotopes such as lutetium-177 (177Lu) or yttrium-90 (90Y). As the FAPI tracers contain the universal DOTA-chelator, a theranostic approach also seems feasible.