de Jong Marion, Mather Stephen, Maina Theodosia
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands -
Barts Cancer Institute, Queen Mary University of London, London, UK.
Q J Nucl Med Mol Imaging. 2017 Jun;61(2):145-152. doi: 10.23736/S1824-4785.17.02974-0.
Detection of useful cellular targets has strongly stimulated personalized tumor-targeted imaging and therapy approaches, also involving synthesis and evaluation of nuclear imaging probes with potential for clinical applications. Reviews of preclinical and translational studies concerning such probes, including radiolabeled antibodies, nanobodies, affibodies, peptides, small molecule inhibitors, and nanoparticles, are presented in this issue. As most tracers described in these articles have been developed for the field of cancer imaging and radionuclide therapy, the current article on preclinical studies will focus on cancer research as well. The main steps in developing a nuclear probe for clinical application for radionuclide imaging and therapy, after identification of a suitable molecular target on tumor cells, comprise: 1) synthesis and radiolabeling of the probe; 2) in vitro characterization, such as the evaluation of target binding affinity; 3) in vivo evaluation to assess the biodistribution and tumor targeting capability, for radionuclide therapy purposes also dosimetry studies to determine the absorbed doses and efficacy; 4) radiolabeled probes that successfully pass such tests as well as toxicological studies may enter clinical evaluation. For preclinical testing of radiolabeled probes various relevant in vitro and in vivo models dedicated to oncological research have been developed along with preclinical imaging platforms, including positron emission tomography (PET) and single photon emission computed tomography (SPECT) systems, in combination with magnetic resonance imaging (MRI) or computed tomography (CT). These developments hold great promise for fast translation of new candidate probes from preclinical validation into the clinic. This overview article describes preclinical studies typically being performed to bring a new radiopharmaceutical into clinical oncology practice. It also aims to raise awareness of confounding factors during translation of preclinical studies and ways to overcome them.
有用细胞靶点的检测极大地推动了个性化肿瘤靶向成像和治疗方法的发展，这也涉及到具有临床应用潜力的核成像探针的合成与评估。本期发表了关于此类探针的临床前和转化研究综述，包括放射性标记抗体、纳米抗体、亲和体、肽、小分子抑制剂和纳米颗粒。由于这些文章中描述的大多数示踪剂都是为癌症成像和放射性核素治疗领域开发的，因此当前这篇关于临床前研究的文章也将聚焦于癌症研究。在确定肿瘤细胞上合适的分子靶点后，开发用于放射性核素成像和治疗临床应用的核探针的主要步骤包括：1）探针的合成与放射性标记；2）体外表征，如靶点结合亲和力评估；3）体内评估，以评估生物分布和肿瘤靶向能力，对于放射性核素治疗目的，还需进行剂量学研究以确定吸收剂量和疗效；4）成功通过此类测试以及毒理学研究的放射性标记探针可进入临床评估。为了对放射性标记探针进行临床前测试，已经开发了各种专门用于肿瘤学研究的相关体外和体内模型以及临床前成像平台，包括正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）系统，并与磁共振成像（MRI）或计算机断层扫描（CT）相结合。这些进展为将新的候选探针从临床前验证快速转化到临床带来了巨大希望。这篇综述文章描述了为将一种新的放射性药物引入临床肿瘤学实践通常所进行的临床前研究。它还旨在提高人们对临床前研究转化过程中混杂因素的认识以及克服这些因素的方法。
