Takalloobanafshi Ghazaleh, Kukreja Aditi, Hicks Justin W
Department of Chemistry, Western University, London, ON, Canada.
Cyclotron and Radiochemistry Facility, Lawson Health Research Institute, London, ON, Canada.
Front Nucl Med. 2022 Aug 16;2:963698. doi: 10.3389/fnume.2022.963698. eCollection 2022.
Imaging biomarkers have changed the way we study Alzheimer's disease and related dementias, develop new therapeutics to treat the disease, and stratify patient populations in clinical trials. With respect to protein aggregates comprised of amyloid-β plaques and tau neurofibrillary tangles, Positron Emission Tomography (PET) has become the gold standard imaging modality for quantitative visualization. Due to high infrastructural costs, the availability of PET remains limited to large urban areas within high income nations. This limits access to leading edge medical imaging, and potentially access to new treatments, by millions of rural and remote residents in those regions as well as billions of people in middle- and low-income countries. Single Photon Emission Computed Tomography (SPECT) is a more widely available imaging alternative with lower infrastructural costs and decades of familiarity amongst nuclear medicine professionals. Recent technological advances have closed the gap in spatial resolution and quantitation between SPECT and PET. If effective SPECT radiotracers were available to visualize amyloid-β plaques, geographic barriers to imaging could be circumvented. In this review, we will discuss past efforts to develop SPECT radiotracers targeting amyloid-β plaques which incorporate the most used radionuclide in nuclear medicine: technetium-99m (Tc; = 6.01 h; γ = 140 keV). While reviewing the various chemical scaffolds and chelates employed, the focus will be upon the impact to the pharmacological properties of putative Tc-based amyloid-targeting radiotracers.
影像生物标志物改变了我们研究阿尔茨海默病及相关痴呆症的方式，改变了我们开发治疗该疾病的新疗法以及在临床试验中对患者群体进行分层的方式。对于由淀粉样β斑块和tau神经原纤维缠结组成的蛋白质聚集体，正电子发射断层扫描（PET）已成为定量可视化的金标准成像方式。由于基础设施成本高昂，PET的可用性仍然仅限于高收入国家的大城市地区。这限制了数百万农村和偏远地区居民以及中低收入国家数十亿人口获得前沿医学影像的机会，也可能限制他们获得新治疗方法的机会。单光子发射计算机断层扫描（SPECT）是一种更广泛可用的成像替代方法，基础设施成本较低，并且核医学专业人员对其已经熟悉了数十年。最近的技术进步缩小了SPECT和PET在空间分辨率和定量方面的差距。如果有有效的SPECT放射性示踪剂可用于可视化淀粉样β斑块，那么成像的地理障碍就可以被克服。在这篇综述中，我们将讨论过去开发针对淀粉样β斑块的SPECT放射性示踪剂的努力，这些示踪剂包含核医学中最常用的放射性核素：锝-99m（Tc；半衰期 = 6.01小时；γ = 140 keV）。在回顾所采用的各种化学支架和螯合剂时，重点将放在对假定的基于Tc的淀粉样靶向放射性示踪剂药理性质的影响上。
