Quantitative distribution of radiolabeled 5-Aminosalicylic acid enemas in patients with left-sided ulcerative colitis

Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with^99mTc and to quantitate the distribution of [^99mTc]5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5-ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending, transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of [^99mTc]5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P<0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P< 0.05) and at 2 hr (P< 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume [^99mTc]5-ASA enemas reliably reach the area of inflammation.Supported by a grant from Reid-Rowell, Inc.     

Radioiodination and biological evaluation of nizatidine as a new highly selective radiotracer for peptic ulcer disorder detection

Nizatidine has been labeled using [¹²⁵I] with chloramine‐T as oxidizing agent. Factors such as the amount of oxidizing agent, amount of substrate, pH, reaction temperature, and reaction time have been systematically studied to optimize the iodination. Biodistribution studies indicate the suitability of radioiodinated nizatidine as a novel tracer to image stomach ulcer. Radioiodinated nizatidine may be considered a highly selective radiotracer for peptic ulcer imaging.     

Solid dispersion and effervescent techniques used to prepare docetaxel liposomes for lung-targeted delivery system: in vitro and in vivo evaluation

A lung-targeting liposomal docetaxel was developed to improve therapeutic index and to reduce side effects. Docetaxel proliposomes composed of docetaxel/Tween-80/Phospholipon 90H/cholesterol/citric acid at molar ratio of 0.18:0.09:3.78:3.78:91.17 were prepared by solid dispersion technique, and then were hydrated with NaHCO₃ solution to obtain docetaxel liposomes by effervescent technique. The stability of proliposomes containing docetaxel, characterization and evaluation of lung-targeting effect of docetaxel liposomes in rabbit were studied. Docetaxel proliposomes were stable at 6?±?2°C for at least 12 months. The particle size, zeta-potential, and entrapment efficiency of the resulted liposomes were 1011?±?22?nm, ?23.7?±?0.26?mv, and 90.12?±?0.36%, respectively. As far as the targeting parameters are concerned, the relative intake rate (R_e) and the ratio of peak concentration (C_e) of lung were 28.91 and 74.28, respectively. Compared with liver, spleen, and kidney, the ratios of targeting efficacy (T_e)_liposomes to (T_e)_injection of lung were increased by a factor of 3.16, 23.00, and 27.83, respectively. In conclusion, the negatively charged docetaxel liposomes with diameter of about 1 µm described in this study have favorable lung-targeting effect and are a promising lung-targeting carrier.     

卡铂碳包铁纳米笼壳聚糖纳米球在正常大鼠体内的靶向分布研究

 目的 观察卡铂碳包铁纳米笼壳聚糖纳米球 (C-Fe@CN-CN) 经肝动脉注射结合磁场引导下，在正常大鼠体内的组织分布情况。 方法 SD 大鼠 80 只，随机均分为卡铂组（ A 组）和 C-Fe@CN-CN 结合磁场组（ B 组）。肝动脉插管后， A 组注入卡铂溶液； B 组注入 C-Fe@CN-CN 分散液，以肝左叶为靶区，施加磁场 30 min 。分别于相应时间点采集标本，测定组织中卡铂浓度，观察 C-Fe@CN-CN 在各组织沉积情况。另将 C-Fe@CN-CN 用 ⁹⁹ Tc 标记后，观察体内放射性核素分布情况。 结果 B 组靶区肝卡铂峰浓度 (<>c_max)38.47 μg·g^-1 ，为非靶区肝（ 14.79 μg·g^-1 ）的 2.6 倍，为 A 组肝（ 4.98 μg·g^-1 ）的 7.7 倍。 48 h 时 B 组靶区肝卡铂浓度 3.11 μg·g^-1 ，为非靶区肝（ 0.35 μg·g^-1 ）的 8.9 倍， A 组肝卡铂浓度已低于检测限。 B 组肾、脾和肺 <> c _max 分别为 29.94 ， 1.54 和 1.76 μg·g^-1 ， A 组分别为 37.78 ， 2.14 和 2.34 μg·g^-1 ， 2 组差异有显著性。组织切片显示， C-Fe@CN-CN 聚集于靶区肝细胞间和肝窦中，非靶区肝内少见 C-Fe@CN-CN 的聚集， 其他 脏器内未见聚集的 C-Fe@CN-CN 。核素扫描显示，放射性核素浓集于靶区肝， 其他 脏器分布很少。 结论 C-Fe@CN-CN 在体内具有良好的磁靶向性和缓释性，能选择性聚集于磁靶区的细胞间隙，平稳释放药物，成倍提高靶区药物浓度，延长维持时间，同时显著性降低 其他 器官的药物浓度。     

Preservation of small extracellular vesicles for functional analysis and therapeutic applications: a comparative evaluation of storage conditions

Extracellular vesicles (EVs) are nanovesicles involved in multiple biological functions. Small EVs (sEVs) are emerging as therapeutics and drug delivery systems for their contents, natural carrier properties, and nanoscale size. Despite various clinical application potentials, little is known about the effects of storage conditions on sEVs for functional analysis and therapeutic use. In this study, we evaluated the stability of sEVs stored at 4 °C, −20 °C, and −80 °C up to 28 days and compared them to fresh sEVs. Also, the effect of freeze-thawing circles on the quantity of sEVs was assessed. We found that different storage temperatures, along with shelf life, impact the stability of sEVs when compared to freshly isolated sEVs. Storage changes the size distribution, decreases quantity and contents, and impacts cellular uptake and biodistribution of sEVs. For functional studies, isolated sEVs are suggested to be analyzed freshly or stored at 4 °C or −20 °C for short-term preservation depending on study design; but −80 °C condition would be more preferable for long-term preservation of sEVs for therapeutic application.     

乳糖化人生长激素在小鼠体内的组织分布和药代动力学

目的　研究乳糖化人生长激素 (hGH L)在小鼠体内的组织分布和药代动力学特征。方法　用放射性核素体内示踪技术研究体内分布 ,用放射免疫分析 (RIA)技术研究药代动力学。并对比研究人生长激素 (hGH)。结果　12 5I hGH L具有明显的趋肝性 ,肝最大摄取率为 6 8 83% ,约为12 5I hGH的 2倍。hGH L的血药时曲线下面积 (AUC为32 6 86 9)和在血清的平均驻留时间 (MRT为 2 1 37min)均小于hGH (AUC为 36 913 0 8,MRT为 2 4 98min) (P <0 0 0 5 ) ;而靶器官肝脏的hGH L分布半衰期T12 α( 1 84min)、清除半衰期T12 β( 11 0 9min)小于hGH (T12 α2 11min ,T12 β75 6 5min) (P <0 0 0 5 ) ,其AUC( 176 2 1 9) >hGH( 12 148 2 ) (P <0 0 0 5 )。结论　hGH L可望成为提高hGH治疗儿童生长激素缺乏症的新药     

Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent

Necrosis-avid agents are a class of compounds that selectively accumulate in the necrotic tissues after systemic administration, which can be used for in vivo necrosis imaging and targeted therapies. In order to search for a necrosis-avid tracer agent with improved drugability, we labelled iodine-131 on sennoside B (SB) as a naturally occurring median dianthrone compound. The necrosis targetability and clearance properties of ¹³¹I-SB were evaluated in model rats with liver and muscle necrosis. On SPECT/CT images, a “hot spot” in the infarcted liver lobe and necrotic muscle was persistently observed at 24?h and 72?h post-injection (p.i.). Gamma counting of the tissues of interest revealed a radioactivity ratio of necrotic to viable liver at 4.6 and 3.4 and of necrotic to viable muscle at 7.0 and 8.8 at 24?h and 72?h p.i., respectively. The good match of autoradiographs and fluoromicroscopic images with corresponding histochemical staining suggested preferential uptake of ¹³¹I-SB in necrotic tissue. Pharmacokinetic study revealed that ¹³¹I-SB has an elimination half-life of 8.6?h. This study indicates that ¹³¹I-SB shows not only prominent necrosis avidity but also favourable pharmacokinetics, which may serve as a potential necrosis-avid diagnostic agent for assessment of tissue viability.