​Immunotherapy has been used in oncology for the past ten years, raising great hopes for the treatment of certain cancers. It involves "awakening" the immune system to destroy the tumor, i.e. using the tumor microenvironment as its own "vaccine" by injecting drugs that stimulate immunity against cancer cells. Such drugs, known as immune checkpoint blockers (ICBs, see box), are generally administered intravenously. Despite the promising efficacy of ICBs, the resistance of certain tumors and adverse effects linked to the body's inappropriate immune response hamper their success in cancer treatment.

To circumvent this problem, intra-tumoral administration of immunotherapies has emerged as a potential solution, aiming to mitigate side effects through reduced systemic exposure while increasing efficacy by improving local bioavailability. The number of clinical trials based on intra-tumoral immunotherapy has increased considerably over the last ten years, sometimes leading to spectacular therapeutic effects. However, a thorough study of the local and systemic distribution of ICBs after intra-tumoral administration, as well as their impact on distant tumors, remains crucial to optimize their therapeutic potential.

In this study, the BioMaps laboratory's ONCO team, in collaboration with Dr Lambros Tselikas from the Interventional Radiology Department and the Immunotherapy Translational Research Laboratory at the Gustave Roussy Institute, combined their expertise in immunoPET (Positron Emission Tomography) and interventional radiology to dynamically assess the distribution patterns of a zirconium-89-labeled ICB, administered intravenously and intratumorally in tumor-bearing mice. ImmunoPET monitoring of the radiolabeled drug indicates that its local bioavailability is higher after intra-tumoral injection and that systemic exposure in healthy tissues is reduced with equivalent accumulation and increased efficacy in distant, non-injected tumors compared to intravenously-treated mice.

These results underline the valuable contribution of immunoPET imaging and pharmacokinetic modeling as tools that can be used in clinical practice to support drug development and improve interventional radiology.

Contacts : charles.truillet@universite-paris-saclay.fr 
or lambros.tselikas@gustaveroussy.fr