gms | German Medical Science

Identification of biomarkers that allow patient stratification, monitoring of disease progression and response to treatment is one of the major challenges of molecular imaging and the central paradigm of theranostics. The non-invasive imaging method positron emission tomography (PET) hold great promise in personalized medicine as it allows for identifying individual patients prior to treatment initiation, which (over)express a certain molecular target of interest.

The 18-kDa mitochondrial translocator protein (TSPO) is a promising candidate for a theragnostic approach of gliomas as its expression can be quantified with PET because it is highly expressed in astrocytomas but there is low expression in the normal brain. A recent clinical study proposed TSPO as a target for selective delivery of anticancer drugs into glioma cells [1].

PET tracers for ABC transporters could be useful to preselect cancer patients or epilepsy patients with increased ABC transporter activity who will benefit from treatment with ABC transporter modulating drugs or surgical procedures [2].

In psychiatric disorders DNA polymorphisms have a major influence on the inter-individual variation in pharmacotherapeutic response. The personalized genetic profile refines dosage and confirms drug-to-cellular target interaction. Personalized DNA expression is further regulated by the silencing and activation of genes which has great potential to modulate and to be modulated by pharmacotherapy. Imaging has great potential to provide the means to visualize epigenetic changes in the brain. A preclinical imaging study targeting enzymes involved with gene silencing could be visualized by PET/CT/MRI. The results were subsequently confirmed by post-mortem tissue immunohistochemistry. These new methodologies are paving the way to an objective diagnosis and response to treatment for both AD and major depressive disorder [3]. Furthermore, response to the antidepressant substances (es)citalopram can be predicted with a 11C-DASB PET scan by calculating the ratio between serotonin transporter binding in the amygdala and habenula and binding in the median raphe nucleus [4].

The impact of PET in personalized medicine could be increased by the production of designer PET probes with exquisite sensitivity that can profile key biological processes that are specific to a disease. However, the challenge for the PET field will be its capability to produce and supply cost-effective PET-radioligands to the wider community.