Near-infrared II theranostic agents for the diagnosis and treatment of Alzheimer's disease.

BACKGROUND: Near-infrared II theranostic agents have gained great momentum in the research field of AD owing to the appealing advantages. Recently, an array of activatable NIR-II fluorescence probes has been developed to specifically monitor pathological targets of AD. Furthermore, various NIR-II-mediated nanomaterials with desirable photothermal and photodynamic properties have demonstrated favorable outcomes in the management of AD. METHODS: We summerized amounts of references and focused on small-molecule probes, nanomaterials, photothermal therapy, and photodynamic therapy based on NIR-II fluorescent imaging for the diagnosis and treatment in AD. In addition, design strategies for NIR-II-triggered theranostics targeting AD are presented, and some prospects are also addressed. RESULTS: NIR-II theranostic agents including small molecular probes and nanoparticles have received the increasing attention for biomedical applications. Meanwhile, most of the theranostic agents exhibited the promising results in animal studies. To our surprise, the multifunctional nanoplatforms also show a great potential in the diagnosis and treatment of AD. CONCLUSIONS: Although NIR-II theranostic agents showed the great potential in diagnosis and treatment of AD, there are still many challenges: 1) Faborable NIR-II fluorohpores are still lacking; 2) Biocompatibility, bioseurity and dosage of NIR-II theranostic agents should be further revealed; 3) New equipment and software associated with NIR-II imaging system should be explored.

Utilize multi-metabolic parameters as determinants for prediction of skeletal muscle mass quality in elderly type2 diabetic Chinese patients.

BACKGROUND: Sarcopenia, an age-related disorder characterized by loss of skeletal muscle mass and function, is recently recognized as a complication in elderly patients with type 2 diabetes mellitus (T2DM). Skeletal muscles play a crucial role in glycemic metabolism, utilizing around 80% of blood glucose. Accordingly, we aimed to explore the relationship between glucose metabolism and muscle mass in T2DM. METHODS: We employed the AWGS 2019 criteria for diagnosing low muscle mass and 1999 World Health Organization (WHO) diabetes diagnostic standards. This study included data of 191 individuals aged 60 and above with T2DM of Shanghai Pudong Hospital from November 2021 to November 2022. Fasting C-peptide (FPCP), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) and postprandial 2-hour C-peptide (PPCP), glycated hemoglobin A1c (HbA1c), glycated albumin (GA), serum lipids spectrum, renal and hepatic function, hemoglobin, and hormone were measured. Based on the findings of univariate analysis, logistic regression and receiver operating characteristic (ROC) curves were established. RESULTS: Participants with low muscle mass had significantly lower alanine and aspartate aminotransferase, and both FPCP and PPCP levels (P < 0.05). Compared with those without low muscle mass, low muscle mass group had significantly higher FPG, HbA1c, GA levels (P < 0.05). Body fat (BF, OR = 1.181) was an independent risk factor for low muscle mass. PPCP (OR = 0.497), BMI (OR = 0.548), and female (OR = 0.050) were identified as protective factors for low skeletal muscle. The AUC of BMI was the highest, followed by the PPCP, gender and BF (0.810, 0.675, 0.647, and 0.639, respectively), and the AUC of the combination of the above four parameters reached 0.895. CONCLUSIONS: In this cross-sectional study, BMI, Female, and PPCP associated with T2DM were protective factors for low muscle mass. BF was associated with T2DM and risk factor for low muscle mass.

Pharmacokinetics and Disposition of Contezolid in Humans: Resolution of a Disproportionate Human Metabolite for Clinical Development.

Contezolid (MRX-I), a novel oxazolidinone antibiotic, was recently approved for the treatment of serious Gram-positive infections. The pharmacokinetics and disposition of [14C]contezolid were investigated in a single-dose human mass balance study. Cross-species comparison of plasma exposure for contezolid and metabolites was performed, and the safety of the disproportionate metabolite in human was evaluated with additional nonclinical studies. After an oral administration of 99.1 µCi/602-mg dose of [14C]contezolid, approximately 91.5% of the radioactivity was recovered in 0 to 168 h postdose, mainly in urine followed by that in feces. The principal metabolic pathway of contezolid in human comprised an oxidative ring opening of the 2,3-dihydropyridin-4-one fragment into polar metabolites MRX445-1 and MRX459, with recovery of approximately 48% and 15% of the dose, respectively, in urine and feces. Contezolid, MRX445-1, and MRX459 accounted for 68.0%, 19.5%, and 4.84% of the plasma exposure of the total radioactivity, respectively. Metabolites MRX445-1 and MRX459 were observed in disproportionately larger amounts in human plasma than in samples from rat or dog, the rodent and nonrodent species, respectively, used for the general nonclinical safety assessment of this molecule. This discrepancy was resolved with additional nonclinical studies, wherein the primary metabolite, MRX445-1, was further characterized. The no-observed-adverse-effect level (NOAEL) of MRX445-1 was determined as 360 mg/kg body weight/day in a 14-day repeat-dose test in pregnant and nonpregnant Sprague Dawley rats. Furthermore, MRX445-1 exhibited no antibacterial activity in vitro. Thus, MRX445-1 is not expected to exert clinically relevant pharmacology and toxicity.

Efficacy and safety of 188Re-HEDP in lung cancer patients with bone metastases: a randomized, multicenter, multiple-dose phase IIa study.

PURPOSE: To investigate the pain-relieving effect and safety of three different doses of 188Re-hydroxyethylidine diphosphonate (HEDP) in patients with lung cancer and bone metastases. METHODS: For this randomised, phase 2 and multicenter trial, we enrolled patients with lung carcinoma and multifocal bone metastases and excluded patients who had received bisphosphonates or external-beam radiotherapy within the previous 4 weeks. Fifty-four patients were randomized to receive a single injection of 188Re-HEDP, at doses of 30, 40 or 50 MBq/kg (interval, 12 weeks). Patients were followed-up by assessment of numerical rating scale (NRS) score, global quality of life (QOL) score and adverse events (AEs). ANOVA analysis, Chi-Squared test and LSD-t test were used in this study. RESULTS: Significantly decreased NRS scores relative to baseline were observed in 40 MBq/kg group (Week 0 vs. Week 12: 6.0 ± 1.4 vs. 4.8 ± 2.5, P = 0.033) and 50 MBq/kg group (Week 0 vs. Week 12: 5.5 ± 1.5 vs. 4.5 ± 2.9, P = 0.046). Significant change of global QOL score from baseline was observed in 40 MBq/kg group at week 8 (global QOL score: P = 0.024, pain score: P = 0.041) and 50 MBq/kg group (pain score: P = 0.021) at week 12. No patients withdrew trial because of AEs in three groups. CONCLUSIONS: 188Re-HEDP at dose of 40 and 50 MBq/kg was generally effective to alleviate pain and improve QOL in lung cancer patients with painful bone metastases. 188Re-HEDP was safe and well-tolerated.

Prognostic impact of circulating tumor cells in patients with ampullary cancer.

Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4',6-diamidino-2-phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45-/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2-5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7-7.3, p < 0.001) were both associated with shorter disease-free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2-6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8-8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.

Assessment of the Bone Mineral Content in the Mandible by Dual-Energy X-Ray Absorptiometry to Evaluate Short-Term Change.

With the objective of being able to assess response to disease or clinical treatment, the densitometry community has long sought the ability to assess short-term change in bone density. The mandible, known to have a high bone turnover, an increased vascularity, and a greater susceptibility to osteoclastic and osteoblastic activities, has long been suggested but has fallen short as a site from which to monitor an early change in the response to a treatment or a disease. The current study developed a method to assess bone density in the superimposed left and right mandibles. Examining a skull in a positioning platform showed that studies between -5.0° and +12.5° from the preferred 0° orientation generated studies that were statistically similar to studies in the preferred orientation. After establishing the distribution of bone density in the mandibles, a software was developed that would execute a search for an area of intermediate content within the body and ramus regions of the mandible; in subsequent studies of the same individual, the analysis software would place the body and ramus regions in the same location without operator dependence. Studies in a population of subjects showed that the density in the body and ramus regions varied independently and that the density in these regions was independent of age. Repeat studies with repositioning showed repeatability of 1.73% and 2.44% for the body and ramus, resulting in computed least significant change limits of 4.84% for the body and 6.83% for the ramus. Examining 45 subjects undergoing treatment for osteoporosis up to over 46 wk showed 22 (49%) subjects with an increase in 1 of the mandible sites, suggesting a benefit from treatment, whereas 12 (27%) subjects showed a decrease in both mandible sites, suggesting a poor response to treatment. We conclude that applying the methodology and allowing the software to locate and define regions of interest allow assessments of change in the bone mineral content at the mandible that will reflect early changes occurring with disease or treatment.

Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity.

BACKGROUND: Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function. METHODS: Immunohistochemical staining and/or autoradiography staining were used to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and TH levels in the striatum. Using a stereotyped behavior rating scale, we evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization. RESULTS: Repeated METH administration induced obvious stereotyped behavior and neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly attenuated METH-induced stereotyped responses, and interdicted METH-induced changes in the levels of DAT, D2R and TH expression. Treatment with JTT after METH administration restored DAT, D2R and TH expression to normal levels. CONCLUSIONS: Our results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.

Circulating Tumor Cells as a Biomarker in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIMS: Circulating tumor cells (CTCs) are valuable in both basic research and clinical application for cancer management. In the current study, we evaluated the diagnostic value of CTCs in pancreatic ductal adenocarcinoma (PDAC). METHODS: In total, 143 blood samples from 95 consecutively diagnosed PDAC patients and 48 healthy donors were collected. Combined data from immunostaining of CD45, DAPI and fluorescence in situ hybridization (FISH) with chromosome 8 centromere (CEP8) probe were used to identify CTCs. Cells with features of CD45-/DAPI+/CEP8>2 were detected as CTCs. RESULTS: CTCs were classified as triploid, tetraploid and multiploid based on chromosome 8 copy number. CTC subtype composition was significantly different among groups. Both subtype number and total CTC number were significantly increased in PDAC patients, compared to healthy controls. Total CTC number had 75.8% sensitivity and 68.7% specificity at a cutoff value of 2 cells/3.2 mL. This study is the first to report that CTC subtype number is also useful in cancer diagnosis. Sensitivity was 53.7% and specificity was 85.4% at a cutoff point of 2 CTC subtypes. The diagnostic value of both total CTC number and CTC subtype number was a little poorer than CA199. CONCLUSIONS: Both CTC subtype and total CTC number may serve as potential biomarkers for PDAC.

[Bone Tomography Scan Optimization in SPECT/CT Equipment of Nuclear Medicine].

Objective: To study and search for a balance between the image quality and acquisition speed in tomography of whole body bone scan. Methods: Adjustments of acquisition conditions were carried out gradualy every two months since April 2014. The qualities of fused SPECT/CT images were diagnosed by three doctors. Then the picture would be evaluated comprehensively by analyzing image quality and image resolution after adjusting image acquisition conditions. Results: Seven kinds of image acquisition conditions taken were in line with diagnostic requirements. The third method is extended to clinical work best. Conclusion: To obtain a high colection effi ciency, parameters of bone tomography acquisition can be set a frame of 5 seconds, total 64 (5.625o), automatic probe close and continuous scanning. Also recommends the use of "continuous" instead of "step and shoot" approach in bone SPECT acquisition. tomography, emission-computed, single-photon, bone tomography, program optimization.

A sodium alginate intervention strategy to enhance therapeutic effects of bone-targeted alpha therapy via remodeling 223RaCl2 distribution.

Radium-223 dichloride is the first approved alpha particle-emitting radiopharmaceutical for patients with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. A large percentage of intestinal enrichment and a slow clearance rate were the main causes of gastrointestinal adverse events after 223RaCl2 administration. The molecular weight of sodium alginate in aqueous solution was determined to be 656 kDa. Sodium alginate exhibits a higher affinity for adsorbing Ra2+ compared to other metal ions belonging to the second main group. Sodium alginate as low as 0.5 g/rat reduced intestinal damage by remodeling 223RaCl2 distribution without affecting bone resorption. Intestinal villi were preserved and enterocyte activity was maintained after sodium alginate intervention. Sodium alginate reduced DNA oxidative damage and lipid peroxidation and maintained endogenous antioxidant status by increasing superoxide dismutase levels and total antioxidant capacity. Furthermore, sodium alginate treatment mitigated DNA damage and apoptosis. The administration of sodium alginate effectively maintained the integrity of the intestinal microbiota, which had undergone perturbations due to radiation exposure. This study demonstrated that sodium alginate could be applied to reduce the adverse effects caused by radiation exposure to the intestine during 223RaCl2-treated and reduced intestinal damage resulted from 223RaCl2 accumulation without affecting bone uptake.

18F-FP-CIT dopamine transporter PET findings in the striatum and retina of type 1 diabetic rats.

PURPOSE: Noninvasive methods used in clinic to accurately detect DA neuron loss in diabetic brain injury and diabetic retinopathy have not been reported up to now. 18F-FP-CIT is a promising dopamine transporter (DAT) targeted probe. Our study first applies 18F-FP-CIT PET imaging to assess DA neuron loss in the striatum and retina of T1DM rat model. METHODS: T1DM rat model was induced by a single intraperitoneal injection of streptozotocin (STZ) (65 mg kg-1, ip). 18F-FP-CIT uptake in the striatum and retina was evaluated at 4 weeks, 8 weeks and 12 weeks after STZ injection. The mean standardized uptake value (SUVmean) and the maximum standardized uptake value (SUVmax) were analyzed. Western blot was performed to confirm the DAT protein levels in the striatum and retina. RESULTS: PET/CT results showed that the SUV of 18F-FP-CIT was significantly reduced in the diabetic striatum and retina compared with the normal one from 4-week to 12-week (p < 0.0001). Western blots showed that DAT was significantly lower in the diabetic striatum and retina compared to the normal one for all three time points (p < 0.05). The results from Western blots confirmed the findings in PET imaging studies. CONCLUSIONS: DA neuron loss in the striatum and retina of T1DM rat model can be non-invasively detected with PET imaging using 18F-FP-CIT targeting DAT. 18F-FP-CIT PET imaging may be a useful tool used in clinic for DR and diabetic brain injury diagnosis in future. The expression level of DAT in striatum and retina may act as a new biomarker for DR and diabetic brain injury diagnosis.

Integrated Analysis of Chromatin and Transcriptomic Profiling Identifies PU.1 as a Core Regulatory Factor in Microglial Activation Induced by Chronic Cerebral Hypoperfusion.

In addition to causing white matter lesions, chronic cerebral hypoperfusion (CCH) can also cause damage to gray matter, but the underlying molecular mechanisms remain largely unknown. In order to obtain a better understanding of the relationship between gene expression and transcriptional regulation alterations, novel upstream regulators could be identified using integration analysis of the transcriptome and epigenetic approaches. Here, a bilateral common carotid artery stenosis (BCAS) model was established for inducing CCH in mice. The spatial cognitive function of mice was evaluated, and changes in cortical microglia morphology were observed. RNA-sequencing (RNA-seq) and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were performed on isolated mouse cortical brain tissue. Then, a systematic joint analysis of BCAS hypoperfusion-induced cortex-specific RNA-seq and ATAC-seq was conducted in order to assess the extent of the correlation between the two, and PU.1 was found to be greatly enriched through motif analysis and transcription factor annotation. Also, the core regulatory factor PU.1 induced by BCAS hypoperfusion was shown to be colocalized with microglia. Based on the above analysis, PU.1 plays a key regulatory role in microglial activation induced by CCH. And the transcriptome and epigenomic data presented in this study can help identify potential targets for future research exploring chronic hypoperfusion-induced brain injury.

Development of a Novel 18F-Labeled Probe for PET Imaging of Estrogen Receptor ß.

Estrogen receptor beta (ERß) is an important ER subtype that plays crucial roles in many physiological and pathological disorders. Herein, we developed the probe [18F]PVBO for in vivo ERß targeted PET imaging and obtained promising results. The nonradioactive PVBO showed a 12.5-fold stronger binding affinity to ERß than to ERα in vitro. In vitro assays revealed the specific uptake of [18F]PVBO by DU145 cells. The uptake of [18F]PVBO by DU145 xenografts increased during the 120 min dynamic scanning, with a maximum uptake of 2.80 ± 0.30% ID/g. Based on time activity curves (TACs), the injection of [18F]PVBO with unlabeled PVBO or ERB-041 resulted in a significant signal reduction with the tumor/muscle (T/M) ratio <1 at 30, 60, 75, and 120 min post-injection (p < 0.05). [18F]PVBO demonstrates the feasibility of noninvasively imaging ERß-positive tumors by small-animal PET and provides a new strategy for visualizing ERß in vivo.

Relationship Between Sporadic Renal Cysts and Renal Function Detected by Isotope Renography in Type 2 Diabetes.

Purpose: This study aimed to reveal the relationship between the volume of sporadic renal cysts and renal function in patients with type 2 diabetes (T2D). Materials and Methods: One hundred and seventy-one patients that underwent renal imaging and other routine examinations at the Shanghai Pudong Hospital were included in this study. The Gates' method of glomerular filtration rate (GFR) was measured by 99mTc-DTPA renal dynamic imaging in addition to the eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Results: Our results showed that BMI, total iGFR, and eGFR showed significant differences between patients with T2D with or without SRC (p < 0.05). Spearman correlation analysis showed that cyst volume was positively correlated with Scr and gender but not iGFR (p > 0.05). The total iGFR positively correlated with eGFR (r = 0.83, p < 0.0001) and negatively with Scr (r = -0.78, p < 0.0001), age (r = -0.43, p < 0.0001), duration of T2D (r = -0.25, p = 0.001), and BMI (r = -0.21, p = 0.006) but not gender (r = -0.03, p = 0.668). The multilinear regression model revealed that gender (ß = 0.346, p < 0.001), iGFR (ß = -0.705, p < 0.001), and serum uric acid (ß = 0.195, p = 0.032) were independent predictors of Scr. Moreover, we observed a significant increase in Scr in males (p < 0.05). Finally, we found that the split kidney function reflected by iGFR and related parameters such as time to peak (PTT) and half time of excretion (excrete t1/2) did not mutually distinguish from each other significantly whether they are measured in patients with renal cysts or in those without renal cysts (p > 0.05). Conclusion: Our preliminary results suggest that in T2D, SRCs may be a renal complication of diabetic nephropathy. Although we found that the patients with renal cysts may display reduced iGFR, the volume of simple cysts seems not to exacerbate renal insufficiency. Isotope renography is a useful tool to evaluate the split kidney functions in diabetic patients who acquire single-side cysts.

Development of Mitochondria-Targeted Small-Molecule Dyes for Myocardial PET and Fluorescence Bimodal Imaging.

Mitochondria-targeting positron emission tomography (PET) and fluorescent dual-modal probes are rarely reported. As one of the most promising lipophilic cations, F16 and its derivatives (F16s) have never been used for myocardial imaging. In this work, 14 F16s are synthesized and evaluated for cardiac imaging. In vitro cell fluorescence imaging revealed that the lead probe 5MEF is precisely localized in the mitochondria of cardiomyocytes. In addition, it shows excellent ex vivo fluorescence imaging quality with the heart-to-muscle and heart-to-liver ratios up to ∼2. Furthermore, the radiofluorinated probe 18F-5MEF is successfully prepared and shows a high initial heart uptake of 8.66 ± 0.34 % ID/g at 5 min post injection. It displays a high heart imaging performance, a long retention time in the heart, and a low background in the most normal tissues as revealed by PET. To our knowledge, this is the first time novel F16 analogues are designed and developed for myocardial dual-modal imaging.

Dysregulated RUNX1 Predicts Poor Prognosis by Mediating Epithelialmesenchymal Transition in Cervical Cancer.

OBJECTIVE: Runt-related transcription factor 1 (RUNX1) has been proven to be over-expressed and vital in many malignancies. However, its role in cervical cancer is still unclear. METHODS: Some online databases (Oncomine, GEPIA, UALCAN, LinkedOmics, and others) were used to explore the expression level, prognostic significance, and gene mutation characteristics of RUNX1 in cervical cancer. The protein levels of RUNX1 in cervical cancer were measured by immunohistochemistry (IHC). The functional changes of cervical cancer cells were measured in vitro after decreasing RUNX1. RESULTS: Bioinformatic results revealed that RUNX1 was upregulated in cervical cancer compared to normal tissues. Moreover, over-expression of RUNX1 was significantly correlated with cervical cancer patients' clinical parameters (e.g., individual cancer stages, patients' age, nodal metastasis status, and others). Meanwhile, functional enrichment analysis of RUNX1-related genes indicated that RUNX1 was mainly involved in the epithelial-mesenchymal transition (EMT) process in cervical cancer. Furthermore, RUNX1 may be upregulated by hsamiR-616-5p and hsa-miR-766 identified by miRDB, TargetScan, and miRWalk. Finally, RUNX1 was upregulated in cervical cancer compared to normal tissues by IHC in collected cervical cancer samples. The invasion and migration abilities of cervical cancer cells were significantly reduced by repressing EMT after knocking down RUNX1 in vitro. CONCLUSION: RUNX1 was highly expressed in cervical cancer, and upregulated RUNX1 could significantly promote the invasive abilities of cervical cancer cells by inducing EMT. Therefore, RUNX1 may be a potential biomarker for early diagnosis and targeted therapy of cervical cancer.

Computed Tomography Density and ß-Amyloid Deposition of Intraorbital Optic Nerve May Assist in Diagnosing Mild Cognitive Impairment and Alzheimer's Disease: A 18F-Flutemetamol Positron Emission Tomography/Computed Tomography Study.

Objective: The aim was to study whether the computed tomography (CT) density and ß-amyloid (Aß) level of intraorbital optic nerve could assist in diagnosing mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: A total of sixty subjects were recruited in our study, including nine normal control (NC) subjects (i.e., 4 men and 5 women), twenty four MCI subjects (i.e., 11 men and 13 women), and twenty seven AD subjects (i.e., 14 men and 13 women). All subjects conducted 18F-flutemetamol amyloid positron emission tomography (PET)/CT imaging. Blinded to the clinical information of the subjects, two physicians independently measured and calculated the standardized uptake value ratio (SUVR) of the bilateral occipital cortex, SUVR of the bilateral intraorbital optic nerve, and CT density of the bilateral intraorbital optic nerve by using GE AW 4.5 Workstation. Results: Between AD and NC groups, the differences of the bilateral intraorbital optic nerve SUVR were statistically significant; between AD and MCI groups, the differences of the left intraorbital optic nerve SUVR were statistically significant. Between any two of the three groups, the differences in the bilateral intraorbital optic nerve density were statistically significant. The bilateral occipital SUVR was positively correlated with the bilateral intraorbital optic nerve SUVR and negatively correlated with the bilateral intraorbital optic nerve density. Bilateral intraorbital optic nerve SUVR was negatively correlated with the bilateral intraorbital optic nerve density. The area under the receiver operating characteristic (ROC) curve of multiple logistic regression was 0.9167 (for MCI vs. NC) and 0.8951 (for AD vs. MCI). The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores were positively associated with the intraorbital optic nerve density and were negatively associated with the intraorbital optic nerve SUVR. The regression equation of MoCA was y = 16.37-0.9734 × x 1 + 0.5642 × x 2-3.127 × x 3 + 0.0275 × x 4; the R 2 was 0.848. The regression equation of MMSE was y = 19.57-1.633 × x 1 + 0.4397 × x 2-1.713 × x 3 + 0.0424 × x 4; the R 2 was 0.827. Conclusion: The CT density and Aß deposition of the intraorbital optic nerve were associated with Aß deposition of the occipital cortex and the severity of cognitive impairment. The intraorbital optic nerve CT density and intraorbital optic nerve Aß deposition could assist in diagnosing MCI and AD.

Regional cerebral perfusion in patients with amnestic mild cognitive impairment: effect of cerebral small vessel disease.

OBJECTIVE: To explore the effort of cerebral small vessel disease (CSVD) on regional cerebral perfusion in patients with mild cognitive impairment (MCI) using NeuroGam™ software and evaluate the capability of brain perfusion single photon emission computed tomography (SPECT) in distinguishing MCI with and without CSVD. METHODS: 34 amnestic MCI subjects entered this study, conducting neuropsychological tests, MRI and 99mTechnetium ethyl cystine dimer brain perfusion SPECT imaging. All subjects were divided into those with CSVD and those without CSVD. Perfusion value was measured with Brodmann area (BA) mapping in these two groups. Automated software (NeuroGam™) was used for semi-quantitative analyses of perfusion value and comparison with normal database. RESULTS: Compared with normal database, perfusion levels in BAs 23-left, 28 and 36-left of MCI without CSVD group had great deviations, while perfusion levels in BAs 21, 23, 24, 25, 28, 36, 38 and 47-left of MCI with CSVD group had great deviations. Furthermore, compared with CSVD group, there was significantly lower perfusion value in BA 7-left (P < 0.001) in MCI without CSVD group. CONCLUSIONS: CSVD could interact with pathological changes related to AD, exacerbating hypoperfusion in BAs 21, 23, 28, 36, 38 while compensating for cerebral blood perfusion disorder in BA 7-left in MCI patients. Meanwhile, MCI patients with CSVD shared similar hypoperfusion with vascular cognitive impairment (VCI) in BAs 24, 25 and 47L. Brain perfusion SPECT may help improve our ability to differentiate MCI with and without CSVD.

Azide-Dye Unexpected Bone Targeting for Near-Infrared Window II Osteoporosis Imaging.

Azide is an important chemical functional group and has been widely used in chemical biology. However, the impact of azide on the in vivo behaviors of compounds has been rarely studied. Herein, azide was introduced into a fluorescent dye for the near-infrared window two (NIR-II) bone imaging. Specifically, we designed and synthesized the small-molecule NIR-II dyes, N3-FEP-4T capped with azide and FEP-4T without azide capping. In vitro assays revealed that N3-FEP-4T showed 5- and 5.6- times higher hydroxyapatite accumulation and macrophage uptake than those of FEP-4T, respectively. Moreover, N3-FEP-4T displayed higher bone uptakes and much better bone NIR-II imaging quality, demonstrating the specific bone-targeting ability of the azide-containing probe. N3-FEP-4T was then further successfully used for osteoporosis NIR-II imaging. Overall, our study provides insights into the impact of azide on the in vivo behavior of azide-containing compounds and opens a new window for biological application of azide.

Radium-223 in Asian patients with castration-resistant prostate cancer with symptomatic bone metastases: A single-arm phase 3 study.

AIM: Radium-223, a targeted alpha therapy, is approved widely for the treatment of patients with metastatic castrate-resistant prostate cancer, based on a pivotal phase 3 study in predominantly white patients. We investigated the efficacy and safety of radium-223 in Asian patients with castrate-resistant prostate cancer and metastatic bone disease. METHODS: This multicenter, prospective, single-arm, open-label phase 3 trial evaluated the efficacy and safety of the standard radium-223 regimen (55 kBq/kg every 4 weeks for six cycles) in patients from Asian countries. The primary endpoints were the safety and overall survival. RESULTS: A total of 226 patients were enrolled and received at least one dose of radium-223. Median overall survival was 14.0 months (95% confidence interval [CI], 11.2-17.4). Median time to total alkaline phosphatase and prostate-specific antigen progression were 7.5 (95% CI, 6.8-7.7) and 3.6 (95% CI, 3.1-3.7) months, respectively. Median skeletal-related event-free survival was 26.0 months (95% CI, 12.6-not reached). Grade ≥3 treatment-emergent adverse events were reported in 103 (46%) of 226 patients, with anemia being the most common event (34 [15%] patients). Grade ≥3 drug-related treatment-emergent adverse events occurred in 39 (17%) of 226 patients. Serious treatment-emergent adverse events were reported in 65 (29%) of 226 patients. Seven (3%) patients had an adverse event leading to death; none were considered to be related to radium-223. CONCLUSION: The results of this study support the use of the standard radium-223 regimen for the treatment of Asian patients with castrate-resistant prostate cancer and symptomatic bone metastases.