Radiopharmacy.

The emerging trend in cancer therapy is to enhance cytotoxic immune response by activating cytotoxic cells to achieve effective killing of malignant cells and to reprogram myeloid cells toward an anti-tumor phenotype, representing the current foundations of cancer immunotherapies. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. But, despite impressive tumor effects and extended patient survival, not all patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. I aim to establish a strong Radiopharmacy research group addressing these needs, with a primary interest in developing radiopharmaceuticals for molecular imaging of biomarkers/targets that can contribute to the use of immunotherapy in the most effective way, maximizing the likelihood of response. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations due to the intrinsic tumor heterogeneity and the latter are invasive. In addition, conventional imaging modalities have proven challenging to monitor early responses to cancer immunotherapy and fail to provide any biological insight of the immune cells. To overcome some of these issues, the use of a noninvasive, sensitive, and quantitative molecular imaging technique such as positron emission tomography (PET) using specific radiotracers can provide non-invasive and longitudinal whole-body monitoring of immune responses. Hence, I have put three strategies forward. First, the development of radiopharmaceuticals targeting cysteine protease activity. Given the relevance of their immunoregulatory roles, imaging of cysteine protease activity may prove useful for the design of optimized immunotherapies. Second, the use B-cell maturation antigen (BCMA)-targeted immunoPET to monitor tumor burden, interrogate target availability and assess treatment response of patients with multiple myeloma. Third, immunoPET imaging of the co-stimulatory CD27/CD70 pathway is expected to shed light on the heterogeneous target expression observed between patient tumors, thereby increasing the success of cancer immunotherapies with immunomodulatory monoclonal antibodies and paving the way for novel therapeutic approaches. The experimental set-up will be determined in a project-by-project manner but will typically involve the design and (radio-)chemical synthesis of radiopharmaceuticals, as well as in vitro and in vivo validation strategies in relevant tumor cells and mouse models of cancer.

Keywords:RADIOPHARMACY

Disciplines:Radiopharmacy