Radiology Department, University Hospital , Nantes Cedex , France ; Le Centre Régional de Recherche en Cancérologie Nantes/Angers, Centre national de la recherche scientifique, Université de Nantes , Nantes Cedex , France.
Front Oncol. 2013 Jun 20;3:159. doi: 10.3389/fonc.2013.00159. eCollection 2013.
During the past two decades, considerable research has been devoted to radionuclide therapy using radiolabeled monoclonal antibodies and receptor binding agents. Conventional radioimmunotherapy (RIT) is now an established and important tool in the treatment of hematologic malignancies such as Non-Hodgkin lymphoma. For solid malignancies, the efficacy of RIT has not been as successful due to lower radiosensitivity, difficult penetration of the antibody into the tumor, and potential excessive radiation to normal tissues. Innovative approaches have been developed in order to enhance tumor absorbed dose while limiting toxicity to overcome the different limitations due to the tumor and host characteristics. Pretargeting techniques (pRIT) are a promising approach that consists of decoupling the delivery of a tumor monoclonal antibody (mAb) from the delivery of the radionuclide. This results in a much higher tumor-to-normal tissue ratio and is favorable for therapy as well and imaging. This includes various strategies based on avidin/streptavidin-biotin, DNA-complementary DNA, and bispecific antibody-hapten bindings. pRIT continuously evolves with the investigation of new molecular constructs and the development of radiochemistry. Pharmacokinetics improve dosimetry depending on the radionuclides used (alpha, beta, and Auger emitters) with prediction of tumor response and host toxicities. New constructs such as the Dock and Lock technology allow production of a variety of mABs directed against tumor-associated antigens. Survival benefit has already been shown in medullary thyroid carcinoma. Improvement in delivery of radioactivity to tumors with these pretargeting procedures associated with reduced hematologic toxicity will become the next generation of RIT. The following review addresses actual technical and clinical considerations and future development of pRIT.
在过去的二十年中，已经投入了相当多的研究用于使用放射性标记的单克隆抗体和受体结合剂进行放射性核素治疗。常规放射免疫疗法（RIT）现在已成为治疗非霍奇金淋巴瘤等血液恶性肿瘤的重要手段。对于实体恶性肿瘤，由于放射敏感性较低，抗体难以穿透肿瘤以及正常组织可能受到过度辐射，因此 RIT 的疗效并不理想。为了克服由于肿瘤和宿主特征引起的不同限制，已经开发了创新的方法来提高肿瘤吸收剂量，同时限制毒性。靶向前技术（pRIT）是一种很有前途的方法，它包括将肿瘤单克隆抗体（mAb）的递送与放射性核素的递送分离。这导致肿瘤与正常组织的比率大大提高，这对治疗和成像都很有利。这包括基于亲和素/链霉亲和素-生物素，DNA-互补 DNA 和双特异性抗体-半抗原结合的各种策略。pRIT 随着新的分子构建体的研究和放射化学的发展而不断发展。根据所使用的放射性核素（α，β和俄歇发射器），药代动力学可改善剂量学，从而预测肿瘤反应和宿主毒性。诸如 Dock and Lock 技术之类的新构建体允许生产针对肿瘤相关抗原的各种 mAB。已经在甲状腺髓样癌中显示出生存获益。通过这些靶向前程序改善放射性物质向肿瘤的输送，并减少血液毒性，将成为下一代 RIT。以下综述涉及实际的技术和临床注意事项以及 pRIT 的未来发展。
