RADIOIMMUNOTHERAPY AND EXTRACORPOREAL ADSORPTION THERAPY STUDIES IN MACAQUES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究评估了放射标记抗体治疗作为改善血液恶性肿瘤骨髓移植预后的一种手段。迄今为止，大多数人类临床经验是使用碘标记和钇标记的抗体。虽然这种疗法的初始反应率很高，但大多数患者随后复发。我们的努力旨在通过消除未能到达目标组织并留在血液中导致非目标组织损伤的辐射活性的比例，提高这种治疗方式的疗效并减少毒性。我们使用一种称为体外吸附疗法（ECAT）的方法。这包括通过将血液循环到含有一种特殊材料的柱中，这种材料可以捕获放射性分子，然后将血液返回到循环中，从而去除循环中未与目标组织结合的抗体部分。我们初步研究的目的是证明注射放射性标记抗体和ECAT过程可以安全进行，并且我们可以复制在其他地方观察到的结果。具体来说，我们试图证明血液可以有效地清除未结合的放射性同位素，通过使用ECAT过滤系统。此外，我们的目标是表明，与正常组织相比，这一过程将提高辐射传递到靶细胞的比例。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study evaluated radiolabeled antibody therapy as a means to improve the outcome of bone marrow transplantation for hematologic malignancies. The majority of the human clinical experience to date is with iodine-labeled and yttrium-labeled antibodies. Although the initial response rates to this therapy have been high, most patients subsequently relapse. Our efforts are aimed at improving the efficacy and diminishing the toxicity of this treatment modality by removing the proportion of radiation activity that fails to reach the target tissues and remains in the bloodstream, leading to non-target tissue damage. We use a process called extracorporeal adsorption therapy (ECAT). This consists of removing the portion of antibody that is in the circulation unbound to target tissues by cycling the blood into a column containing a special material that traps the radioactive molecules and then returns the blood back into the circulation. The objective of our pilot study is to demonstrate that the injection of radiolabeled antibody and the ECAT procedure could be performed safely, and that we could reproduce the results observed elsewhere. Specifically we seek to show that the blood can be effectively cleared of unbound radioisotope, by using the ECAT filtration system. Further, we aim to show that this procedure will improve the ratio of radiation delivered to target cells, as compared to normal tissues.