Evaluation of a Novel Amyloid Plaque SPECT Tracer for Diagnosing AD

描述（由申请人提供）：这是R01申请的重新提交，旨在评价新型放射性药物123I IMPY（IMPY），该药物可与阿尔茨海默病（AD）患者的淀粉样斑块结合。这种示踪剂是第一种用于单光子发射计算机断层扫描（SPECT）的示踪剂，可广泛应用于AD患者的诊断和随访。我们的初步研究表明，IMPY用于人类受试者是安全的，并具有良好的生物分布特征。我们还获得了4例AD患者和3例对照的初始SPECT数据，这些数据显示了组间的明显差异。然而，为了更好地建立IMPY的诊断准确性，需要进行更大规模的试验。由于AD的临床诊断通常很难做出，因此有必要将IMPY SPECT结果与用于检测AD的其他措施（包括18 F氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）和其他生物化学生物标志物）的结果进行比较。我们计划在四年内对60名AD患者和60名对照受试者进行IMPY SPECT扫描。将在多个水平上分析这些扫描，包括输入函数、动力学、示踪剂摄取和简化定量的最佳方法。将确定使用IMPY SPECT定量IMPY摄取和区分AD患者与对照的最佳方法。这些数据将有助于确定AD患者和对照组的IMPY摄取范围，以区分这两组。利用受试者操作者特征曲线，我们将确定优化诊断准确性的最佳方法。靶向A2斑块的示踪剂是近年来AD诊断的研究热点，IMPY是第一个123I标记的化合物。考虑到SPECT成像的广泛可用性，IMPY可能具有用于AD患者的诊断和随访的实质性应用，特别是当这些患者用设计用于减弱疾病的病理生理过程的药物治疗时。靶向A2斑块用于诊断阿尔茨海默病（AD）的放射性示踪剂已成为最近的主要研究焦点。这些示踪剂可以帮助AD的早期检测，并可能监测与治疗干预相关的变化。考虑到SPECT成像的广泛可用性，123 I IMPY可能在AD患者的诊断和随访中具有实质性应用，因此，确定其能力和评价图像的最佳方法的需要对于这种潜在重要的淀粉样蛋白成像示踪剂的未来使用至关重要。

DESCRIPTION (provided by applicant): This is a resubmission of an R01 application designed to evaluate the novel radiopharmaceutical, 123I IMPY (IMPY), that binds to the amyloid plaque in patients with Alzheimer's disease (AD). This tracer is the first of its kind for use with single photon emission computed tomography (SPECT) and may have wide applications for the diagnosis and follow up of AD patients. Our preliminary studies demonstrated that IMPY was safe to use in human subjects and had a good biodistribution profile. We also obtained initial SPECT data on 4 AD patients and 3 controls which showed a clear difference between the groups. However, a larger scale trial is necessary in order to better establish the diagnostic accuracy of IMPY. Since the clinical diagnosis of AD is often difficult to make, it is necessary to compare IMPY SPECT results to those of other measures for detecting AD including 18F fluorodeoxyglucose (FDG) positron emission tomography (PET), and other biochemical biomarkers. We plan to perform IMPY SPECT scans on 60 AD patients and 60 control subjects over a four year period. These scans will be analyzed on a number of levels including input function, kinetics, tracer uptake, and best methods to simplify quantitation. The best method for quantifying IMPY uptake and distinguishing AD patients from controls using IMPY SPECT will be determined. This data will help establish the range of uptake of IMPY in AD patients and controls in order to differentiate the two groups. Using receiver operator characteristic curves, we will determine the best method for optimizing diagnostic accuracy. Tracers that target the A2 plaques have been a recent focus of research in the diagnosis of AD and IMPY represents the first 123I labeled compound. Given the wide availability of SPECT imaging, IMPY may have substantial applications for the diagnosis and follow up of AD patients, especially when such patients are treated with medications designed to attenuate the pathophysiological course of the disease. Radioactive tracers that target the A2 plaques for diagnosing Alzheimer's disease (AD) have been a recent primary focus of research. These tracers can aid in the early detection of AD and potentially monitor changes associated with therapeutic interventions. Given the wide availability of SPECT imaging, 123I IMPY may have substantial applications for the diagnosis and follow up of AD patients, and thus, the need to determine its capabilities and the best method for evaluating images is crucial for the future use of this potentially important amyloid imaging tracer.