Episode 2, Biomarker expression: important factors for the success of radiotheranostics
Radiomolecular ligands are directed towards biomarkers that are overexpressed on cancer cells. This enables specific delivery of radioactivity to tumor cells.
Important is that these biomarkers are not or at very low levels expressed on other cells, preventing accumulation of radioactivity in healthy tissues. This allows precise imaging, and safe and effective treatment.
Even though overexpression of a biomarker might occur often in a certain cancer type, not all patients suffering of this respective cancer type have biomarker positive tumors. An advantage of radiotheranostics is that the radiomolecular ligand can first be used for imaging to determine whether there is expression of the biomarker and whether the expression is sufficient, before the radiomolecular ligand is applied for therapeutic purposes. This information can also be used to optimize the dose of radiomolecular ligand therapy for each individual patient.
In a similar way possible uptake of the radiomolecular ligand in healthy organs can also be determined, and proper measurements can be taken to prevent the occurrence of side effects. This includes measures such as dose adjustment and co-administration of “protective agents”. The latter is for example used for kidney protection since many radiomolecular ligands are renally excreted and as a consequence thereof accumulate in this organ. Multiple “protective agents” exist to prevent nephrotoxicity during radiomolecular ligand therapy, for example co-administration of a combination of amino acids. The amino acids work by preventing reabsorption of the radiomolecular ligands from the kidney filtrate (pre-urine) back into your bloodstream. By doing so, the radiomolecular ligands are cleared faster and do not remain at the site of the kidneys too long, thereby reducing the chance of severe side effects.
Next to differences in biomarkers expression between patients, individual cancer cells within a tumor can also have different levels of biomarker expression. An advantage of radiomolecular ligand therapy is that even though some of the cancer cells might not express the biomarker or have low expression of the biomarker, radiation from neighboring cells can still hit the cell, causing a cytotoxic effect. This is the so-called cross-fire effect.
The possibility to visualize (level of) biomarker expression, the ability to optimize dose based on biomarker-expression level, the use of agents to protect healthy organ uptake and the advantage of cross-fire radiation, are unique characteristics of radiotheranostics that make this approach highly personalized, tumor-specific, effective and safe.
Next to biomarker expression, a few other factors are important for the success of radiotheranostics such as the radionuclide of choice, properties of the radiomolecular ligands and application strategies. These topics will be discussed in the next blog episodes.