Evaluation of a Novel Amyloid Plaque SPECT Tracer for Diagnosing AD

描述（由申请人提供）：这是重新提交的R01申请，旨在评估与阿尔茨海默病（AD）患者的淀粉样斑块结合的新型放射性药物123I IMPY （IMPY）。该示踪剂是首个用于单光子发射计算机断层扫描（SPECT）的示踪剂，可能在AD患者的诊断和随访中有广泛的应用。我们的初步研究表明，IMPY在人类受试者中使用是安全的，并且具有良好的生物分布特征。我们还获得了4名AD患者和3名对照者的初始SPECT数据，显示了组间的明显差异。然而，为了更好地建立诊断准确性，需要更大规模的试验。由于阿尔茨海默病的临床诊断往往难以做出，因此有必要将IMPY SPECT结果与其他检测阿尔茨海默病的方法（包括18F氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）和其他生化生物标志物）的结果进行比较。我们计划在四年的时间里对60名AD患者和60名对照受试者进行IMPY SPECT扫描。这些扫描将在多个层面上进行分析，包括输入功能，动力学，示踪剂摄取和简化定量的最佳方法。将确定量化IMPY摄取和使用IMPY SPECT区分AD患者与对照组的最佳方法。该数据将有助于确定AD患者和对照组中IMPY摄取的范围，以便区分两组。利用接收算子特征曲线，我们将确定优化诊断准确性的最佳方法。靶向A2斑块的示踪剂已成为最近AD诊断研究的焦点，而IMPY是首个123I标记化合物。鉴于SPECT成像的广泛可用性，IMPY可能在AD患者的诊断和随访中具有重要应用，特别是当这些患者接受旨在减轻疾病病理生理过程的药物治疗时。针对A2斑块诊断阿尔茨海默病（AD）的放射性示踪剂已成为近期研究的主要焦点。这些示踪剂可以帮助早期发现阿尔茨海默病，并可能监测与治疗干预相关的变化。鉴于SPECT成像的广泛可用性，123I IMPY可能在AD患者的诊断和随访中有大量应用，因此，确定其能力和评估图像的最佳方法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.