PET Imaging of Innate Immune Activation Using 11C Radiotracers Targeting GPR84.

Chronic innate immune activation is a key hallmark of many neurological diseases and is known to result in the upregulation of GPR84 in myeloid cells (macrophages, microglia, and monocytes). As such, GPR84 can potentially serve as a sensor of proinflammatory innate immune responses. To assess the utility of GPR84 as an imaging biomarker, we synthesized 11C-MGX-10S and 11C-MGX-11Svia carbon-11 alkylation for use as positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding of both radiotracers to hGPR84-HEK293 cells than that of parental control HEK293 cells. Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro. In vivo assessment of each radiotracer via PET imaging of healthy mice illustrated the superior brain uptake and pharmacokinetics of 11C-MGX-10S compared to 11C-MGX-11S. Subsequent use of 11C-MGX-10S to image a well-established mouse model of systemic and neuro-inflammation revealed a high PET signal in affected tissues, including the brain, liver, lung, and spleen. In vivo specificity of 11C-MGX-10S for GPR84 was confirmed by the administration of GLPG1205 followed by radiotracer injection. When compared with 11C-DPA-713-an existing radiotracer used to image innate immune activation in clinical research studies-11C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of 11C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of 11C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology.

First Superferromagnetic Remanence Characterization and Scan Optimization for Super-Resolution Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is a sensitive, high-contrast tracer modality that images superparamagnetic iron oxide nanoparticles, enabling radiation-free theranostic imaging. MPI resolution is currently limited by scanner and particle constraints. Recent tracers have experimentally shown 10× resolution and signal improvements with dramatically sharper M-H curves. Experiments show a dependence on interparticle interactions, conforming to literature definitions of superferromagnetism. We thus call our tracers superferromagnetic iron oxide nanoparticles (SFMIOs). While SFMIOs provide excellent signal and resolution, they exhibit hysteresis with non-negligible remanence and coercivity. We provide the first quantitative measurements of SFMIO remanence decay and reformation using a novel multiecho pulse sequence. We characterize MPI scanning with remanence decay and coercivity and describe an SNR-optimized pulse sequence for SFMIOs under human electromagnetic safety limitations. The resolution from SFMIOs could enable clinical MPI with 10× reduced scanner selection fields, reducing hardware costs by up to 100×.