Investigating the efficacy of nasal administration for delivering magnetic nanoparticles into the brain for magnetic particle imaging.

This study explored the effectiveness of nasal administration in delivering magnetic nanoparticles into the brain for magnetic particle imaging of target regions. Successful delivery of iron oxide nanoparticles, which serve as contrast agents, to specific sites within the brain is crucial for achieving magnetic particle imaging. Nasal administration has gained attention as a method to bypass the blood-brain barrier and directly deliver therapeutics to the brain. In this study, we investigated surface modification techniques for administering magnetic nanoparticles into the nasal cavity, and provided experimental validation through in vivo studies. By compositing magnetic nanoparticles with gold nanoparticles, we enabled additional surface modification via AuS bonds without compromising their magnetic properties. The migration of the designed PEGylated magnetic nanoparticles into the brain following nasal administration was confirmed by magnetization measurements. Furthermore, we demonstrated the accumulation of these nanoparticles at specific target sites using probe molecules immobilized on the PEG terminus. Thus, the efficacy of delivering magnetic nanoparticles to the brain via nasal administration was demonstrated in this study. The findings of this research are expected to contribute significantly to the realization of magnetic particle imaging of target regions within the brain.

Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging ß-Amyloid in Alzheimer's Disease Affected Brain.

In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo[1,2- a]pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of ß-amyloid (Aß). Among the 11 evaluated compounds, 10 showed moderate affinity to Aß(1-42) aggregates, exhibiting half-maximal inhibitory concentrations (IC50) of 14.7 ± 6.07-87.6 ± 39.8 nM. In vitro autoradiography indicated that 123I-labeled triazole-substituted derivatives displayed highly selective binding to Aß plaques in the hippocampal region of Alzheimer's disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all 123I-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging Aß plaques, with the highest selectivity observed for a 1 H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [123I]ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings.

A Novel CYP11B2-Specific Imaging Agent for Detection of Unilateral Subtypes of Primary Aldosteronism.

CONTEXT: Although adrenal vein sampling is the standard method to distinguish unilateral from bilateral forms of primary aldosteronism, it is an invasive and technically difficult procedure. (11)C-metomidate (MTO)-positron emission tomography was reported as a potential replacement for adrenal vein sampling. However, MTO has low selectivity for CYP11B2 over CYP11B1. OBJECTIVE: This study aimed to determine the selectivity of (18)F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of (18)F-CDP2230 is favorable for imaging CYP11B2. METHODS: The IC50 of CDP2230 for the enzymatic activities of CYP11B2 and CYP11B1 was determined using cells with stable expression of either enzyme. In vitro autoradiography of human adrenal sections with aldosterone-producing adenomas was performed to confirm the specific binding ability of (18)F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of (18)F-CDP2230 in rats. RESULTS: Although CDP2230 showed a significantly lower affinity for CYP11B2 and CYP11B1 than did MTO analogues, its selectivity for CYP11B2 over CYP11B1 was higher than that of MTO analogues. In vitro autoradiography revealed that the binding of (18)F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of (123)I-IMTO. Moreover, the biodistribution study showed that (18)F-CDP2230 accumulated in adrenal glands with low background uptake. CONCLUSIONS: Our study showed a high selectivity of (18)F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. (18)F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.

Synthesis and base-pairing properties of C-nucleotides having 1-substituted 1H-1,2,3-triazoles.

Oligonucleotides including C-nucleotides having 1-substitued 1H-1,2,3-triazoles as artificial nucleobases were conveniently synthesized by the post-elongation modification method using the copper(I)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. The base-pairing properties of the triazole nucleobase analogs in forming duplexes with oligonucleotides were investigated by the T(m) experiments.