• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Radiolabeled androgens for imaging and therapy: Radiopharmaceutical investigations and development of animal models.
【24h】

Radiolabeled androgens for imaging and therapy: Radiopharmaceutical investigations and development of animal models.

机译：用于影像学和治疗的放射性标记的雄激素：放射性药物研究和动物模型的开发。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

This work expands our efforts with radiolabeled androgens from diagnostic imaging to approach radiotherapy. A fluorinated androgen under evaluation in humans, 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT), was considered the standard. Two other androgens, 16beta-[ 18F]fluoromibolerone (FMib) and 7alpha-iodo-5alpha-dihydrotestosterone (IDHT) were synthesized as well.;A more suitable animal model for evaluating radiolabeled androgens in vivo than the currently used adult male rat model was developed. The major failing of the rat model is lack of sex hormone binding globulin (SHBG), a plasma protein found in many species, including humans, that may positively affect steroid distribution and metabolism. High affinities for SHBG are now desired, necessitating a primary animal model that simulates SHBG's effects. Four models were evaluated: mature rats administered human SHBG, immature rats, immature rabbits and mature rabbits. Both mature and immature rabbits have circulating SHBG, while immature rats have a related protein, androgen binding protein (ABP). A Positron Emission Tomography (PET) imaging protocol for mature rabbits was developed. FDHT and FMib were compared in this model.;To expand the uses of PET and to permit radiotherapy with halogenated steroids, biomedical cyclotron production of I-124, Br-76 and Br-77, via the (p,n) reaction on Te or Se was investigated. In situ target formation was developed to produce CU2Te or CU2Se ready for irradiation. It was shown that these targets were reusable. An enriched (99.8% Te-124) Cu2Te target was made, irradiated, and the I-124 separated to prepare [124I]IDHT to image a rabbit.;Three human ovarian cancer cell lines, OVCAR-3, SKOV-3 and OV-1063, were evaluated as in vivo tumor bearing models in SCID mice using FDHT to determine the feasibility of androgen based imaging and radiotherapy of ovarian cancer. [125I]IDHT was evaluated in both SC and IP OVCAR-3 tumors. Tumors were imaged using PET and FDHT and using electronic autoradiography with both FDHT and [125I]IDHT.;Additional projects were: (1) development of a novel evaporation apparatus using heated nitrogen to accelerate radioisotope processing; (2) examining the reactivity of p-[18F]fluorophenacyl bromide as a radiolabeling agent for proteins and peptides.
机译：这项工作扩大了我们对放射性标记的雄激素的努力，从诊断成像到放射治疗。在人类中评估的氟化雄激素16β-[18F]氟-5α-二氢睾酮（FDHT）被认为是标准。还合成了另外两种雄激素，即16β-[18F]氟米勃龙（FMib）和7α-碘-5α-二氢睾丸激素（IDHT）。与目前使用的成年雄性大鼠模型相比，更适合于体内评估放射性标记雄激素的动物模型是发达。大鼠模型的主要失败之处在于缺乏性激素结合球蛋白（SHBG），这是一种在许多物种（包括人类）中发现的血浆蛋白，可能对类固醇的分布和代谢产生积极影响。现在需要SHBG的高亲和力，因此需要模拟SHBG效果的主要动物模型。评价了四种模型：施用人SHBG的成熟大鼠，未成熟大鼠，未成熟兔子和成熟兔子。成熟和未成熟的兔子都具有循环SHBG，而未成熟的大鼠具有相关的蛋白质，雄激素结合蛋白（ABP）。开发了用于成熟兔的正电子发射断层扫描（PET）成像协议。在该模型中比较了FDHT和FMib .;为扩大PET的用途并允许使用卤化类固醇进行放射治疗，通过Te上的（p，n）反应的生物医学回旋加速器生产I-124，Br-76和Br-77或硒进行了调查。发展了原位靶的形成以产生准备用于照射的CU 2 Te或CU 2 Se。结果表明，这些目标是可重用的。制备了一个富集（99.8％Te-124）Cu2Te靶，进行辐照，并分离出I-124以制备[124I] IDHT以给兔子成像。;三种人卵巢癌细胞系OVCAR-3，SKOV-3和OV -1063被评估为使用FDHT的SCID小鼠体内荷瘤模型，以确定基于雄激素的卵巢癌显像和放射疗法的可行性。在SC和IP OVCAR-3肿瘤中均评估了[125I] IDHT。使用PET和FDHT以及带有FDHT和[125I] IDHT的电子放射自显影术对肿瘤成像。其他项目是：（1）开发一种使用加热的氮气加速放射性同位素处理的新型蒸发装置； （2）检查对-[18F]氟苯甲酰溴作为蛋白质和肽的放射性标记剂的反应性。

著录项

  • 作者

    Downer, Joanna Beth.;

  • 作者单位

    Washington University in St. Louis.;

  • 授予单位 Washington University in St. Louis.;
  • 学科 Chemistry Pharmaceutical.;Engineering Biomedical.;Health Sciences Radiology.;Health Sciences Oncology.
  • 学位 Ph.D.
  • 年度 1998
  • 页码 158 p.
  • 总页数 158
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号