SPECT BENZODIAZEPINE RECEPTOR IMAGING TO LOCALIZE SEIZURE FOCUS

SPECT 苯二氮卓受体成像以定位癫痫病灶

• 批准号: 5214984
• 负责人: ROBERT INNIS
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5214984
• 关键词: Cercopithecidae; Macaca mulatta; autoradiography; baboons; benzodiazepine receptor; blood flow measurement; computational neuroscience; experimental brain lesion; human subject; human tissue; magnetic resonance imaging; microdialysis; model; neuropharmacology; partial seizure; radiotracer; receptor expression; single photon emission computed tomography; temporal lobe /cortex disorder

PET (Positron Emission Tomography) imaging of the benzodiazepine (BZ) receptor has been reported to localize the area of seizure focus by decreased radioligand uptake compared to contralateral homotypic cortex (Savic et al., 1988). The overall goal of this proposal is to assess the capability of the cost effective SPECT (Single Photon Emission Computed Tomography) technology to localize seizure focus. We will use the high affinity radioligand 123I-Ro16-0154, state-of-the-art SPECT imaging devices, computer program for co-registration of SPECT and MRI images, quantitative receptor autoradiography, compartmental kinetic modeling, and in vivo cerebral microdialysis. Preliminary data are reported on the density of two BZ receptor subtypes in neurosurgically-obtained hippocampal tissue from the seizure focus of patients with temporal lobe epilepsy (TLE) secondary to sclerosis. In comparison to autopsy and neurosurgical control groups, patients with TLE- sclerosis had regionally selective decreases of "central" type and increases of "peripheral" type BZ receptors, and these changes paralleled the regional losses of neurons and proliferation of glia, respectively. Since the PET BZ receptor ligand (11C-Ro15-1788) and our SPECT ligand (123I-Ro16-0154) bind to the "central" type BZ receptor, these results provide neuropathological data supporting the loss of these sites determined with in vivo imaging techniques. Our studies with 123I-Ro16-0154 in non-human primates have shown that it is a high affinity ligand with pharmacological specificity for the BZ receptor; has high brain uptake (10% of injected dose) with only the parent compound and not metabolites entering brain; has high ratios of specific to non-specific binding (approximately 15:1); and demonstrates a long period of relatively stable brain uptake. As the only US site studying this radiopharmaceutical, we have recently begun human studies, which have shown results comparable to those in non-human primates and demonstrated very favorable radiation dosimetry. In addition, we have studied two patients with temporal lobe epilepsy and shown significantly decreased uptake in the temporal lobe on the side of the epileptic focus. Our preliminary results will be extended by comparing the sensitivity of BZ receptor imaging and blood flow to localize seizure focus and by assessing the accuracy and reproducibility of SPECT imaging to measure BZ receptors.

苯二氮卓类 (BZ) 的 PET（正电子发射断层扫描）成像 据报道，受体可以通过以下方式定位癫痫病灶区域： 与对侧同型皮层相比，放射性配体摄取减少 （Savic 等人，1988）。 该提案的总体目标是评估 具有成本效益的 SPECT（单光子发射计算 断层扫描）技术来定位癫痫病灶。 我们将使用高 亲和放射性配体 123I-Ro16-0154，最先进的 SPECT 成像 用于联合配准 SPECT 和 MRI 图像的设备、计算机程序， 定量受体放射自显影、房室动力学模型和 体内脑微透析。 报告了两种 BZ 受体亚型密度的初步数据 通过神经外科手术从癫痫病灶获得的海马组织 继发于硬化的颞叶癫痫（TLE）患者。 在 与尸检组和神经外科对照组相比，TLE 患者 硬化具有“中央”类型的区域选择性减少和 “外周”型 BZ 受体的增加，这些变化是平行的 分别是神经元的区域性损失和神经胶质细胞的增殖。 由于 PET BZ 受体配体 (11C-Ro15-1788) 和我们的 SPECT 配体 (123I-Ro16-0154) 与“中枢”型 BZ 受体结合，这些结果 提供支持这些位点丢失的神经病理学数据 通过体内成像技术确定。 我们对 123I-Ro16-0154 在非人类灵长类动物中的研究表明，它是 对 BZ 具有​​药理学特异性的高亲和力配体 受体；仅母体具有高脑摄取量（注射剂量的 10%） 化合物而非代谢物进入大脑；具有较高的特定比率 非特异性结合（大约 15:1）；并展示了很长一段时间 大脑摄取相对稳定。 作为唯一研究此内容的美国网站 放射性药物，我们最近开始了人体研究，结果表明 结果与非人类灵长类动物的结果相当，并且证明非常 有利的辐射剂量测定。 此外，我们还研究了两名患者 患有颞叶癫痫，并显示出摄取显着减少 颞叶位于癫痫病灶一侧。 我们的初步结果将通过比较 BZ 的敏感性来扩展 受体成像和血流来定位癫痫病灶并通过评估 SPECT 成像测量 BZ 受体的准确性和重现性。