Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targeting axonal potassium channels to image demyelination by positron emission tomography (PET). These channels, which normally reside beneath the myelin sheath, become exposed upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We demonstrate using autoradiography that 4-AP has higher binding in non-myelinated and demyelinated versus well-myelinated CNS regions, and describe a fluorine-containing derivative, 3-F-4-AP, that has similar pharmacological properties and can be labeled with 18F for PET imaging. Additionally, we demonstrate that [18F]3-F-4-AP can be used to detect demyelination in rodents by PET. Further evaluation in Rhesus macaques shows higher binding in non-myelinated versus myelinated areas and excellent properties for brain imaging. Together, these data indicate that [18F]3-F-4-AP may be a valuable PET tracer for detecting CNS demyelination noninvasively.

A 3‐step glioblastoma‐tropic delivery and therapy method using nanoparticle programmed self‐destructive neural stem cells (NSCs) is demonstrated in vivo: 1) FDA‐approved NSCs for clinical trials are loaded with pH‐sensitive MSN‐Dox; 2) the nanoparticle conjugates provide a delayed drug‐releasing mechanism and allow for NSC migration towards a distant tumor site; 3) NSCs eventually undergo cell death and release impregnated MSN‐Dox, which subsequently induces toxicity towards surrounding glioma cells.

There is strong clinical interest in using neural stem cells (NSCs) as carriers for targeted delivery of therapeutics to glioblastoma. Multimodal dynamic in vivo imaging of NSC behaviors in the brain is necessary for developing such tailored therapies; however, such technology is lacking. Here we report a novel strategy for mesoporous silica nanoparticle (MSN)–facilitated NSC tracking in the brain via SPECT. Methods 111In was conjugated to MSNs, taking advantage of the large surface area of their unique porous feature. A series of nanomaterial characterization assays was performed to assess the modified MSN. Loading efficiency and viability of NSCs with 111In-MSN complex were optimized. Radiolabeled NSCs were administered to glioma-bearing mice via either intracranial or systemic injection. SPECT imaging and bioluminescence imaging were performed daily up to 48 h after NSC injection. Histology and immunocytochemistry were used to confirm the findings. Results 111In-MSN complexes show minimal toxicity to NSCs and robust in vitro and in vivo stability. Phantom studies demonstrate feasibility of this platform for NSC imaging. Of significance, we discovered that decayed 111In-MSN complexes exhibit strong fluorescent profiles in preloaded NSCs, allowing for ex vivo validation of the in vivo data. In vivo, SPECT visualizes actively migrating NSCs toward glioma xenografts in real time after both intracranial and systemic administrations. This is in agreement with bioluminescence live imaging, confocal microscopy, and histology. Conclusion These advancements warrant further development and integration of this technology with MRI for multimodal noninvasive tracking of therapeutic NSCs toward various brain malignancies.

Due to their electron-rich aromatic structure, nucleophilic (radio)fluorination of pyridines is challenging, especially at the meta position. In this paper, we describe the first example of direct fluorination of a pyridine N-oxide to produce a metafluorinated pyridine. Specifically, fluorination of 3-bromo-4-nitropyridine N-oxide produced in several minutes 3-fluoro-4-nitropyridine N-oxide in moderate yield at room temperature. This intermediate compound was later converted to 3-fluoro-4-aminopyridine easily by catalytic hydrogenation. Furthermore, this approach was succesfully applied for labeling with fluorine-18. The use of pyridine N-oxides for the preparation of fluoropyridines is unprecedented in the chemical literature and has the potential to offer a new way for the synthesis of these important structures in pharmaceuticals and radiopharmaceuticals.