Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17 alpha-methylestradiol in normal and tumor-bearing rats

Tritiated 17 alpha-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17 alpha-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (Kd = 1.96 x 10(-10)M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 hr after injection. After 30 min the uterine uptake was 1.73% dose/g. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23-30% of the uptake in the uterus. Tritiated 17 alpha-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that 17 alpha-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical.     

[~3H]-乙酰紫草素在小鼠体内的组织分布、排泄及血中分布研究

目的:用氧化燃烧炉样品预处理技术研究[3H]-乙酰紫草素在小鼠体内的组织分布、排泄和血中分布.方法:小鼠单次灌服[3H]-乙酰紫草素后,收集组织、血、尿和粪样,氧化燃烧炉法进行样品预处理,液闪计数仪测定放射性水平.结果:小鼠单次灌胃给[3H]-乙酰紫草素(120 mg/kg,2.96×107 Bq/kg)后,放射性主要分布在胃、肠,其次是胆囊、肝、肾、肺,脑和脊髓分布较少.271 h后从粪中收集到给药剂量的(68.5 ± 3.3)%,尿中收集到(17.6± 3.1)%,粪尿合计(86.1 ± 5.5)%.另对乙酰紫草素在血中存在形式、血细胞和血浆中的分配比例以及与血浆蛋白结合的形式、结合率进行了探索性研究.结论:乙酰紫草素吸收较差;组织分布广泛;排泄较完全;1 h血样中没有检测到原形;血浆、血细胞药物含量分配比约为4∶ 1;人血浆蛋白结合率高;血浆蛋白的结合为共价和疏水作用两种形式并存.     

莫诺苷的大鼠组织分布

目的研究莫诺苷在大鼠组织的分布特征。方法24只雄性sD大鼠随机分为4组,单剂量（30mg／kg）莫诺苷灌胃给药,分别于给药后5,45,120和360min股动脉放血处死动物,解剖取组织。采用高效液相色谱一串联质谱联用法测定莫诺苷浓度。结果大鼠给药5min即在小肠、胃、脾脏、肝脏和心脏达最高值,120min在脂肪组织中达最高值,其余组织均在45min达到最高值,360min后各组织的药物浓度均降至较低水平。结论莫诺苷在大鼠体内的吸收和分布较快,药物入血后在体内各组织分布较为广泛,在组织中的消除亦较快,结果提示药物没有组织蓄积趋势。     

Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi

RATIONALE AND OBJECTIVES: New targeted microbubbles directed to the GPIIb IIIa receptor have been developed. The objective was to determine whether targeting microbubbles to clots would enhance ultrasound imaging. Systematic studies were designed to determine whether in vitro methodology is an acceptable predictor of in vivo efficacy. MATERIALS AND METHODS: Bioconjugate ligands were inserted into lipid-coated membranes of perfluorocarbon gas microbubbles and binding studies performed on activated platelets immobilized on cell culture plates. Targeted microbubble binding to clots in a flow through chamber was also assessed. Finally, microbubble binding studies on arteriolar and venular clots in a mouse cremasteric muscle model were conducted. RESULTS: Binding studies on platelet-immobilized plates demonstrated an affinity for targeted microbubbles versus untargeted microbubbles. Semiquantitative light obscuration techniques helped to measure extent of targeted microbubble binding. Targeted microbubbles similarly bound to platelet clots in the flow model. Finally, studies in the mouse model confirmed binding of targeted microbubbles in both venules and arterioles. CONCLUSION: The use of receptor selective targeted microbubbles improved binding to vascular thrombi in both in vitro and in vivo settings.     

炭疽毒素受体及其与保护性抗原结合机制的研究进展

本文阐述了炭疽毒素的细胞表面受体研究及其与保护性抗原结合分子机制等方面的进展。到目前为止，共发现两种炭疽毒素受体，分别由TEM8和CMG2基因编码。炭疽毒素受体的发现和鉴定时炭疽的病理学研究具有重要的意义，而且体外实验发现的受体与毒素的高亲和力也为受体本身作为炭疽的治疗剂带来了希望。CMG2和PA结合状态晶体结构的解析使我们能够对毒素进入细胞质过程的分子细节有所推论。所建立的理论模型为研究其他类型穿透细胞膜发挥作用的毒素的作用过程提供了重要的参考。     

(3-N-[11C]methyl)spiperone, a ligand binding to dopamine receptors: radiochemical synthesis and biodistribution studies in mice

Carbon-11-labeled 3-N-methylspiperone, a positron-emitting dopamine-receptor antagonist with potential for use in positron emission tomography studies of human neurotransmitter receptors, was synthesized from 11CO2 in 40 min, with a radiochemical yield of approximately 20-40%. The specific activity of the (3-N-[11C]methyl)-spiperone was determined by ultraviolet spectroscopy to be approximately 270 mCi/mumol at the end of synthesis. In in vitro binding experiments, the Ki for 3-N-methylspiperone was found to be approximately 250 pM (against H-3 spiperone). The brain-to-blood ratios in normal ICR mice were 2.8 or greater at the times studied, and the striatum-to-cerebellum ratio at 60 min after injection was 20:1.     

Tissue distribution and stability of metalloporphyrin MRI contrast agents

Mn(III), Fe(III), and Gd(III) complexes of tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and several other porphyrins were evaluated as potential MRI contrast agents. Based on consideration of relaxivity and stability properties in solution, MnTPPS was found to be the compound of choice. At pH 7 the Gd and Mn complexes significantly enhanced the water proton relaxation rate, while the relaxivity of FeTPPS exhibited a significant loss of relaxivity above pH 6 due to oxy-dimer formation. Although GdTPPS exhibited the highest relaxivity in solution, this property was rapidly lost due to dissociation of the metal ion. By contrast MnTPPS remained stable in human plasma after incubation for 9 days. Upon intravenous injection into athymic mice bearing subcutaneous human colon carcinoma xenografts, MnTPPS provided enhanced relaxation of the tissue water in several excised mouse tissues, notably kidney, liver, and tumor. The results at a fixed field (0.25 T) and relaxation dispersion studies showed decreases in water relaxation rates with time for kidney and liver, but an increase for the tumor, with a maximum near 4 days at the highest dose used.     

3′-二甲氨基亚甲基葛根素在大鼠体内组织分布与排泄研究

目的:研究3′-二甲氨基亚甲基葛根素在大鼠体内的组织分布与排泄情况,了解药物在动物体内变化过程,为临床试验提供药代依据.方法:大鼠尾静脉注射3′-二甲氨基亚甲基葛根素(生理盐水溶液,剂量50 mg/kg),采用机械匀浆处理组织.排泄实验是在不同时间点收集全部粪、尿、胆汁样品.用经验证的LC/MS/MS联用测定各组织、粪、尿、胆汁中3′-二甲氨基亚甲基葛根素的含量.结果:大鼠给药后,12 d内从粪中收集到给药剂量的(13.6±2.8)%,尿液中回收到(65.4±11.5)%,粪尿合计(79.0±14.3)%,5 d内胆汁中收集到(14.8±4.4)%.3′-二甲氨基亚甲基葛根素在大鼠各组织中均检测到,大肠内容物、小肠内容物和肝中浓度较高.结论:3′-二甲氨基亚甲基葛根素广泛分布于大鼠各组织中,主要以原形经尿和粪便排泄.     

N-Isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K _d) values of 53 ± 2 and 4687 ± 124 nM and maximum binding capacity (Bmax) values of 7 ± 1 and 133 ± 27 pmol/mg protein (n=5) respectively. The IC₅₀ values of various amines were as follows: IMP, 9 × 10^–5 M; propranolol, 5 × 10^–4 M; haloperidol, 6 × 10^–4 M; ketamine, 9 × 10^–3 M; dopamine, 1 × 10^–2 M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K _d values of 54 ± 2 and 5277 ± 652 nM and Bmax values of 7±1 and 103 ± 21 pmol/mg protein (n = 3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue.Correspondence to: E. Tanaka     

Tissue distribution and kinetics of gadolinium and nephrogenic systemic fibrosis

Gadolinium (Gd) released from Gd-based MR contrast agents is the likely etiologic agent of nephrogenic systemic fibrosis (NSF). The biodistribution and kinetics of both chelated Gd and free Gd³⁺ are reviewed, including demonstrations of Gd in tissues of NSF patients. The purpose of this review is to consolidate the available information on distribution, metabolism, excretion and retention of Gd with particular emphasis on the possible mechanisms in the development of NSF. We also raise serious concern about the growing tissue burden of Gd with the release of Gd from its chelates and its yet unknown consequences. The development of NSF as well as potential long-term consequences of tissue Gd retention represent a part of the spectrum of Gd toxicity.     

山西运城地区115株铜绿假单胞菌的分布及耐药性分析

目的了解山西运城地区铜绿假单胞菌（PA）临床分布及其耐药特点,以指导临床合理用药。方法从临床各种标本中分离、培养铜绿假单胞菌,采用全自动细菌鉴定及药敏测定仪（ATB）进行细菌的鉴定及药敏分析。结果铜绿假单胞菌主要分离于痰液,以呼吸道感染为主,对阿米卡星、头孢他啶、头孢吡肟、环丙沙星、庆大霉素、特治星（哌拉西林/他唑巴坦）耐药率均大于40%,对泰能（亚胺培南/西司他丁）的耐药率较低（27.83%）。结论山西运城地区铜绿假单胞菌仍是医院病原菌感染的主要致病菌之一,且出现多重耐药性,需加强耐药性监测。     

CGEONA对荷LA-795肺腺癌小鼠和正常小鼠放射敏感性的影响

目的 为了寻低低毒有效的放射增敏剂,观察ＣＧＥＯＮＡ（羟基－苯乙烯基锗倍半氧化物钠盐）对荷瘤小鼠和正常小鼠放射敏感性的影响。方法 放射增敏实验用Ｔ－７３９小鼠,肿瘤模型ＬＡ－７９５肺腺癌,采用肿瘤再生长延缓法评价效果;放射防护实验用昆明种小鼠,观察３０ｄ存活率和对造务系统的影响。