RADIOIMMUNOAMPLIFICATION REACTIONS

此应用程序的目的是扩展Summa Medical 公司（SMC）在放射免疫成像（RII）领域的表现 用Tc-99 m标记的抗体在体内检测人 使用外部伽马射线照相术检查恶性肿瘤。 SMC进行了临床试验 在温哥华（加拿大）进行的第一个已知和获批IND试验 Tc-99 m标记的抗人绒毛膜抗体的应用 使用亲和纯化的绵羊多克隆和小鼠促性腺激素（hCG） 单克隆IgG抗体和F（ab '）2片段。 SMC开发了一种新的 放射性标记抗体和抗体片段的技术， Tc-99 m适用于临床研究，可还原为 即时标记“冷”套件。 这些研究的结果已经 令人鼓舞的是， 表达hCG已经在身体的不同部位被证明， RII技术。 然而，该技术的灵敏度可能是 通过增加注射的放射性核素的总百分比来改善， 专门针对肿瘤部位。 因此，SMC根据 SBIR计划测试一种称为放射免疫扩增的新方法， 寻求提高RII技术的灵敏度。 本 应用中，双抗体方法将使用适当的 针对肿瘤相关抗原的单克隆抗体， 通过在一秒的适当时间间隔后给药 将用Tc-99 m放射性标记的抗体，其应靶向 第一抗体 将采用两种单独的动物模型，包括 抗独特型系统，以及表达hCG的人类肿瘤， 在裸鼠体内生长。 SMC还将研究人的体内定位， 在本研究中， 后一种模式。 由于形成的潜在免疫病理学 还将评估体内免疫复合物。 的结果予以 研究将直接关系到这种方法是否会被 在人体临床试验中尝试。 这些研究可能会导致 开发商业上可行的产品， 与目前的RII方法相比具有优势。

The purpose of this application is to extend work that Summa Medical Corporation (SMC) has performed in the area of radioimunnoimaging (RII) with Tc-99m labeled antibodies for the in vivo detection of human malignancy using external gamma scintigraphy. SMC has conducted clinical trials in Vancouver, BC (Canada) under the first known and approved IND application for the use of Tc-99m labeled antibodies to human chorionic gonadotropin (hCG) using affinity pufified sheep polyclonal and murine monoclonal IgG antibodies and F(ab')2 fragments. SMC has developed a new technique for the radiolabeling of antibodies and antibody fragments with Tc-99m that is suitable for the clinical studies and is reducible to instant labeling of "cold" kits. The results of these studies have been very encouraging in that a significant percentage of human tumors expressing hCG have been demonstrated at diverse sites in the body using the RII technique. However, the sensitivity of this technique may be improved by increasing the total percentage of radio nuclide injected that specifically targets to tumor sites. Therefore, SMC is applying under the SBIR program to test a novel approach termed radioimmunoamplification that seeks to increase the sensitivity of the RII technique. In the present application, a double antibody approach is to be tested using appropriate monoclonal antibodies directed against tumor associated antigens, followed by the administration after an appropriate time interval of a second antibody that will be radiolabeled with Tc-99m that should target to the first antibody. Two separate animal models will be employed, including an anti-idiotype system, and a human tumor that expresses hCG that will be grown in nude mice. SMC will also study the in vivo localization of human monoclonal antibodies reactive with hCG and labeled with Tc-99m in this latter model. Potential immunopathology resulting from the formation of immune complexes in vivo will also be assessed. The results of these studies will have direct bearing on whether this type of approach will be attempted in human clinical trials. These studies may lead to the development of commercially viable products demonstrating significant advantage over current approaches to RII.