Development of novel radiopharmaceuticals for non-invasive diagnosis and stratification of cancer patients using positron emission tomography (PET)

Galith Abourbeh, Ph.D.; Hilbert Grievink, Ph.D.; Ofer Shamni, Ph.D.; Tamar Peretz, M.D. and Eyal Mishani, Ph.D

Positron emission tomography (PET) is a non-invasive imaging modality that relies on injection of radioactively labelled compounds (‘radiopharmaceuticals’) for producing 3D whole-body quantitative images of various functional processes. These processes involve specific proteins, such as enzymes and receptors, which are referred to as ‘targets’. The radiopharmaceuticals are designed to specifically bind to these targets, enabling molecular imaging, i.e. visualization and quantification of the expression of proteins of interest. Prof. Mishani and colleagues from the Cyclotron Unit develop radiopharmaceuticals that allow not only selection of patients prior to targeted drug therapy, but could also monitor the target’s expression status during the course of treatment.

Radiopharmaceuticals are used in PET by physicians and scientists to detect and study alterations in functional processes known to be associated with disease. For example, Prof. Mishani and colleagues developed a novel radiopharmaceutical that could allow the non-invasive identification of a subgroup of lung cancer patients, whose tumors express a mutated form of a key protein, and can therefore benefit from targeted treatment strategies that are superior to chemotherapy. Currently, identification of these patients requires invasive tumor biopsies which are costly, time consuming and do not necessarily reflect the molecular/ functional status of distant metastases.

The non-invasive screening of patients using specifically targeted radiopharmaceuticals can aid physicians in detecting specific malignancies, in determining treatment strategies and in monitoring the expression status of specific targets during the course of treatment, and as such can be thought of as a core element of personalized medicine.


PET-CT slice-images of tumor-bearing mice following injection of a novel radiopharmaceutical (tumors are indicated by green arrowheads). Increased accumulation of the radiopharmaceutical in a tumor (depicted with a color scale) identifies it as a tumor that will respond to targeted treatment of lung cancer. Mouse 1 is bearing a targeted therapy-responsive tumor, whereas Mouse 2 is bearing a targeted therapy non-responsive tumor.