RADIORECEPTOR GUIDED SURGERY OF NEURAL CREST TUMORS

放射受体引导的神经嵴肿瘤手术

• 批准号: 6378216
• 负责人: M. Sue O'Dorisio
• 金额: $ 53.02万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-27 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6378216
• 关键词: adolescence (12-20); adult human (21+); autoradiography; bioimaging /biomedical imaging; child (0-11); clinical research; clinical trial phase I; hormone receptor; human subject; human therapy evaluation; iodine; laboratory rat; melanoma; neoplasm /cancer radiation therapy; neoplasm /cancer surgery; neuroblastoma; neuroendocrine system; neurosurgery; pediatric neoplasm /cancer; peptide hormone analog; radionuclide imaging /scanning; radionuclides; receptor binding; somatostatin

DESCRIPTION: (Adapted from the investigator's abstract) Neural crest stem cells differentiate into multiple tissues, including the peripheral and enteric nervous systems, the adrenal medulla, and melanocytes. Neural crest tumors derived from these precursors include neuroblastoma in children, neuroendocrine tumors of the gut and melanoma in adults. Neural crest tumors share common biological features, which may render them susceptible to similar treatments. Our work has demonstrated expression of somatostatin receptors in both primary tumors and cell lines. We have demonstrated the utility of radiolabeled somatostatin analogues in imaging neuroendocrine tumors. Our innovative technique for radioreceptor guided surgery has been utilized to successfully guide surgical extirpation of occult tumor in both adult and pediatric patients with neural crest derived tumors. Preliminary data demonstrates expression of somatostatin receptors in neuroblastoma, neuroendocrine tumors of the gut and melanoma. We therefore hypothesize that somatostatin receptors can be exploited as diagnostic and therapeutic targets in neural crest tumors. We propose to test this hypothesis in animal models of neuroblastoma followed by clinical trials in both male and female children and adults. We have designed and synthesized several unique somatostatin analogues with high affinity and potent physiologic effects at sst1 and sst2. We will characterize their affinity for other somatostatin receptors [sst3, sst4 and sst5] and test their growth inhibitory potential against neuroblastoma call lines and primary tumor cells in culture. Specific sst1 and sst2 analogues will be labeled with 123Iodine for scintigraphy, or 125Iodine for radioreceptor guided surgery will be tested in a xenograft model of disseminated neuroblastoma. Children with neuroblastoma will be entered into a clinical study to test the feasibility and specificity of somatostatin scintigraphy and radioreceptor guided surgery in detection and cytoreduction of neuroblastoma. This will provide image guided surgical therapy of neuroblastoma and will also provide whole body and tumor dosimetry data, which can then be applied to radiotherapy of neuroblastoma using (90)Y-DOTA-peptides, which target somatostatin receptors on malignant cells. Adults with neuroendocrine tumors will be entered into a study to test feasibility and specificity of radioreceptor guided surgery. Patients will be recruited from our nationally recognized, multidisciplinary neuroendocrine tumor clinic to participate in this trial of image guided surgical therapy.

描述：（改编自研究者的摘要）神经嵴干细胞 分化为多种组织，包括外周组织和肠组织 神经系统、肾上腺髓质和黑素细胞。神经嵴肿瘤 源自这些前体的包括儿童神经母细胞瘤、神经内分泌瘤 成人肠道肿瘤和黑色素瘤。神经嵴肿瘤有共同点 生物学特征，这可能使它们容易受到类似治疗的影响。 我们的工作证明了生长抑素受体在原发性和 肿瘤和细胞系。我们已经证明了放射性标记的实用性 生长抑素类似物在神经内分泌肿瘤成像中的应用。我们的创新 放射受体引导手术技术已成功用于 指导成人和儿童患者隐匿性肿瘤的手术摘除 与神经嵴衍生的肿瘤。初步数据表明表达 神经母细胞瘤、肠道神经内分泌肿瘤和生长抑素受体 黑色素瘤。因此，我们假设生长抑素受体可以被利用 作为神经嵴肿瘤的诊断和治疗靶点。我们建议 在神经母细胞瘤动物模型中检验这一假设，然后进行临床研究 在男性、女性儿童和成人中进行的试验。 我们设计并合成了几种独特的生长抑素类似物 sst1 和 sst2 具有高亲和力和强大的生理作用。我们将 表征它们与其他生长抑素受体 [sst3、sst4 和 sst5]并测试它们对神经母细胞瘤的生长抑制潜力 细胞系和培养中的原代肿瘤细胞。具体的 sst1 和 sst2 类似物将 用 123 碘标记用于闪烁扫描，或用 125 碘标记用于放射受体 引导手术将在播散性异种移植模型中进行测试 成神经细胞瘤。 患有神经母细胞瘤的儿童将进入临床研究以测试 生长抑素闪烁显像和放射受体的可行性和特异性 神经母细胞瘤的检测和细胞减灭术的引导手术。这将 提供神经母细胞瘤的影像引导手术治疗，还将提供 全身和肿瘤剂量测定数据，然后可应用于放射治疗 使用 (90)Y-DOTA 肽治疗神经母细胞瘤，该肽靶向生长抑素受体 对恶性细胞。 患有神经内分泌肿瘤的成年人将被纳入一项研究以测试 放射受体引导手术的可行性和特异性。患者将会 从我们国家认可的多学科神经内分泌中心招募 肿瘤诊所参加了本次图像引导手术治疗的试验。