Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma.

Recent studies suggest that BRAF-mutated melanomas in particular respond to dual anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) immune checkpoint inhibition (ICI). Here we identified an over-representation of interleukin (IL)-17-type 17 helper T (T17) gene expression signatures (GES) in BRAF-mutated tumors. Moreover, high baseline IL-17 GES consistently predicted clinical responses in dual-ICI-treated patient cohorts but not in mono anti-CTLA-4 or anti-PD-1 ICI cohorts.

Administration Routes for SSTR-/PSMA- and FAP-Directed Theranostic Radioligands in Mice.

The NETTER-1, VISION, and TheraP trials proved the efficacy of repeat intravenous application of small radioligands. Application by subcutaneous, intraperitoneal, or oral routes is an important alternative and may yield comparable or favorable organ and tumor radioligand uptake. Here, we assessed organ and tumor biodistribution for various radioligand application routes in healthy mice and models of cancer expressing somatostatin receptor (SSTR), prostate-specific membrane antigen (PSMA), and fibroblast activation protein (FAP).

Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression.

Imaging Inflammation with Positron Emission Tomography.

The impact of inflammation on the outcome of many medical conditions such as cardiovascular diseases, neurological disorders, infections, cancer, and autoimmune diseases has been widely acknowledged. However, in contrast to neurological, oncologic, and cardiovascular disorders, imaging plays a minor role in research and management of inflammation. Imaging can provide insights into individual and temporospatial biology and grade of inflammation which can be of diagnostic, therapeutic, and prognostic value.

In vivo biodistribution of calcium phosphate nanoparticles after intravascular, intramuscular, intratumoral, and soft tissue administration in mice investigated by small animal PET/CT.

Calcium phosphate nanoparticles were covalently surface-functionalized with the ligand DOTA and loaded with the radioisotope Ga. The biodistribution of such Ga-labelled nanoparticles was followed in vivo in mice by positron emission tomography in combination with computer tomography (PET-CT). The biodistribution of Ga-labelled nanoparticles was compared for different application routes: intravenous, intramuscular, intratumoral, and into soft tissue.

Imaging inflammation after myocardial infarction: implications for prognosis and therapeutic guidance.

Inflammation after myocardial infarction (MI) has been in the focus of cardiovascular research for several years as it influences the remodeling process of the ischemic heart and thereby critically determines the clinical outcome of the patient. Today, it is well appreciated that inflammation is a crucial necessity for the initiation of the natural wound healing process; however, excessive inflammation can have detrimental effects and might result in adverse ventricular remodeling which is associated with an increased risk of heart failure. Newly emerged imaging techniques facilitate the non-invasive assessment of immune cell infiltration into the ischemic myocardium and can provide greater insight into the underlying complex and dynamic repair mechanisms.