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Immune thrombocytopenia (ITP) is one of the most common acquired immune-mediated bleeding disorders found in children. Prednisone is usually considered a first-line therapeutic agent for ITP in children. Yet, prolonged exposure to prednisone has been associated with certain side effects. This prospective randomized study comparatively assessed the efficacy and safety of short-course high-dose dexamethasone (HDD) and standard prednisone (PDN) as a first-line treatment for children with previously untreated primary ITP. Two hundred eleven children were randomized into the HDD (n = 110) and PDN (n = 101) groups. There was no difference in baseline characteristics between the two groups (p > 0.05). Early response rates were 92.7% and 93% (p = 0.923); initial response rates were 93.6% and 95% (p = 0.658) and durable response rates were 90% and 91% (p = 0.787) in the HDD and PDN groups, respectively. More remission patients in the HDD group compared with the PDN group (86.3% vs. 80.1%) at 12th month after treatment, yet no statistical difference was observed (p = 0.703). Bleeding events were 10.9% and 14.8% (p = 0.105), and bleeding score improvement rates were 78.2% and 76.2% (p = 0.284) in the HDD and PDN groups, respectively. Cushing’s disease, weight gain and infection rates were higher in the PDN group compared to the HDD group (80% vs. 10%, p = 0.001; 74.2% vs. 13.6%, p = 0.001; and 26% vs. 11.8%, p = 0.012) 1 month after treatment. HDD showed non-inferior efficacy and fewer glucocorticoid-related adverse effects compared with PDN. These findings indicated that HDD could be considered as a first-line treatment in children with previously untreated primary ITP, thus replacing standard PDN.

To study the pharmacokinetics, biodistribution, and injection doses of 99mTc-TRODAT-1 in healthy adults. Thirty healthy individuals comprising 15 females and 15 males were randomly divided into three groups and the injection doses of 99mTc-TRODAT-1 of group 1, 2, and 3 were 370 MBq, 740 MBq, and 1110 MBq, respectively. Assessments of subjective symptoms and tests were performed before and after injection. Blood and urine collections and whole-body planar imaging were analyzed at various time points. Bilateral brain striatal SPECT images obtained at 3.5 h PI were assessed visually and semiquantitatively. No serious adverse events or deaths were observed in our study. The pharmacokinetic analysis showed that 99mTc-TRODAT-1 was eliminated rapidly from the circulation, with just about 4% of the injected dose remaining in blood at 1 h post-injection. The mean cumulative urinary excretion over 24 h was just 2.96 ± 0.96%ID. The time-activity curve demonstrated that the radioactivity was mainly in liver and abdomen. The highest absorbed dose was in the dose-limiting organ, liver (20.88 ± 4.45 × 10−3 mSv/MBq). The average effective dose was 5.22 ± 1.05 × 10−3 mSv/MBq. The clarity of striatal images assessed visually in group 1 was worse than that in group 2 and 3. The semiquantitative analysis showed that there were no differences in striatum/cerebellum between the three groups (group 1: 1.77 ± 0.11, group 2: 1.62 ± 0.14, and group 3: 1.75 ± 0.20; P = 0.088). 99mTc-TRODAT-1 was safe to use in humans and showed the status of dopaminergic neurons specifically and clearly. The injection dose we suggested was 740 MBq.

The corresponding author of the article would like to remove "Jian Wang" in the author group.

The aim of this study was to optimize the radiolabeling method of [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) to fulfill the demand of preclinical and clinical application. Optimized labeling conditions were performed by altering the molar ratio of precursor to base (P/B), base species, solvents, reaction temperature, reaction time, and precursor concentration through manual radiosynthesis of [18F]FP-(+)-DTBZ. The conditions with the highest radiochemical yield (RCY) were applied to automated radiosynthesis, and the crude product was purified with a Sep-Pak Plus C18 cartridge. Quality control and stability of [18F]FP-(+)-DTBZ were carried out by HPLC. In vitro cellular uptake and blocking assays were conducted in human neuroblastoma cell line SH-SY5Y. In vivo imaging with small animal positron emission tomography (microPET) was performed with Sprague–Dawley rats. Under the optimized conditions (P/K2CO3 = 1:8, heating at 120 °C for 3 min in dimethyl sulfoxide), an RCY of 88.7 % was obtained with 1.0 mg precursor. The optimized reaction conditions were successfully applied to an automated module and gave a high activity yield (AY) of 30–55 % in about 40 min with a > 99.0 % radiochemical purity (RCP) and a > 44.4 GBq/μmol molar activity (Am). Stability test displayed that the RCP retained > 98.0 % in 8 h in saline and in phosphate buffer saline (PBS, pH 7.4). In vitro cellular uptake assay showed accumulation of [18F]FP-(+)-DTBZ in SH-SY5Y cells, which could be significantly inhibited by vesicular monoamine transporter 2 (VMAT2) inhibitor DTBZ. MicroPET images of rat brain displayed that the striatum showed the highest uptake with a standardized uptake value (SUV) of 3.91 ± 0.30 at ~ 70 min. Co-injection with DTBZ (1.0 mg/kg) resulted in a 75 % decrease of the striatal SUV, confirming the specificity of [18F]FP-(+)-DTBZ to VMAT2. We obtained an optimized radiolabeling method of [18F]FP-(+)-DTBZ and successfully applied it to a commercial available module. The automated synthesis gave a high AY and RCP of [18F]FP-(+)-DTBZ with high and specific binding to VMAT2, facilitating its routine application for VMAT2 tracing.

A new radioiodinated tetrabenazine (TBZ) derivative containing an iodovinyl group at 9-position of TBZ (131I-IV-TBZ, 11a) and the corresponding cold compound IV-TBZ (11b) were synthesized and characterized. Analysis of in vitro autoradiography with rat brain slices showed 11a has a high uptake in the striatum and the uptake could be blocked by known vesicular monoamine transporter 2 (VMAT2) inhibitor. Furthermore, 11b has a competitive binding to VMAT2. These results suggest that 11a has ability to bind to VMAT2 and the binding is specific. Further studies are warranted to assess this radioiodinated TBZ derivative for VMAT2 imaging in vivo.

We studied on the structural requirement of C11b chirality of tetrabenazine (TBZ) analogs as vesicular monoamine transporter 2 (VMAT2) ligands. TBZ analogs (2, 6a, 6b) and 18F-radiolabeled [18F]6a and [18F]6b with eliminated C11b chirality were synthesized and characterized. Competition studies demonstrated that 2, 6a and 6b displayed much lower in vivo VMAT2 bindings than TBZ. MicroPET imaging studies of [18F]6a and [18F]6b showed negligible accumulation in VMAT2-enriched regions as compared with the known VMAT2 ligand 18F-FP-(+)-DTBZ. These results suggest that C11b chirality of TBZ analogs is essential for in vivo VMAT2 binding bioactivity.

A precise and sensitive HPLC method was developed for the determination of p-toluenesulfonoxypropyl-(+)-dihydrotetrabenazine [TsOP-(+)-DTBZ] enantiomeric purity. The effects of mobile phase composition and column temperature on the enantioresolution and analysis time of the enantiomers were investigated. The optimized chiral separation method was performed on a Phenomenex Chirex 3014 column (250 mm × 4.6 mm, particle size 5 μm) using a mobile phase consisting of n-hexane/1,2-dichloroethane/ethanol/trifluoroacetic acid/triethylamine (64/32/4/0.01/0.005 v/v/v/v/v) at a flow rate of 0.8 mL min−1 and a column temperature of 25 °C. The enantiomers were monitored with UV detection at 280 nm, and baseline separation with a resolution higher than 2.0 was achieved within 20 min. The method was validated in terms of linearity, precision, accuracy, robustness, limit of detection (LOD) and limit of quantification (LOQ). The linearity range for the determination of each enantiomer was 0.002–2.0 mg mL−1 (n = 6). Additionally, the LOD and LOQ of TsOP-(+)-DTBZ were 0.15 and 0.50 μg mL−1; those for its enantiomer were 0.18 and 0.60 μg mL−1, respectively. Furthermore, this validated method was successfully applied to analyze three different TsOP-(+)-DTBZ bulk samples. The results demonstrated that the proposed method was simple, rapid, accurate and robust for routine enantiopurity analysis of TsOP-(+)-DTBZ in pharmaceutical research.

2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane ([18F]-FECNT) is a potential dopamine transporter PET imaging agent. However, its current radio-synthesis is tedious and time consuming. In this article, we reported a fully automatic method for the synthesis of [18F] FECNT through only one step, using a TRACERlab FXN module, with decay corrected radiochemical yield of 25 ± 5 % (n = 5). The total synthesis time was 50–55 min. The synthesized [18F]FECNT was evaluated in vivo in Parkinson’s disease model rats.

The title compound, 3-methyl-4-phenyl-5-(2-pyridyl)-1,2,4-triazole was synthesized by reaction of diphenylphosphazoanilide with N-acetyl-N′-(2-pyridoyl)hydrazine. Crystals suitable for X-ray analysis were obtained from a mixed solution of water and ethanol in a one-to-one volume ratio. The crystal is orthorhombic, space group P212121 with crystallographic parameters: a = 19.414(4) A, b = 17.172(3) A, c = 7.4850(15) A, β = 90.00°, μ = 0.079 mm−1, V = 2495.3(8) A3, Z = 8, Dc = 1.258 g/cm3, F(000) = 992, T = 295(2) K. The X-ray results showed that in the crystal structure of the title compound, the 1,2,4-triazole, pyridine and benzene rings are not coplanar. The title compound was synthesized by reaction of diphenylphosphazoanilide with N-acetyl-N′-(2-pyridoyl)hydrazine, and the crystal structure shows that its three aromatic rings (1,2,4-triazole, pyridine and benzene rings) do not share a common plane.

To provide a convenient and facile method to evaluate the radiochemical purity (RCP) of 99mTc-TRODAT-1 in quality control of routine clinical application, a simplified method of single-strip thin layer chromatography (TLC) was developed and validated by high performance liquid chromatography (HPLC). The RCP data of TLC correlated well with HPLC.