Pretherapy 124I-MIBG Dosimetry for Planning 131I-MIBG Neuroblastoma Therapy

用于规划 131I-MIBG 神经母细胞瘤治疗的治疗前 124I-MIBG 剂量测定

• 批准号: 9055673
• 负责人: Youngho Seo
• 金额: $ 35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9055673
• 关键词: Adult; Affect; Animal Model; Animals; Area; Behavior; Beta Particle; Cell Line; Cells; Child; Childhood; Clinical; Clinical Research; Data; Detection; Development; Dose; Drug Kinetics; Embryo; Ensure; Evaluation; Gamma Cameras; Goals; Half-Life; Hour; Human; I131 isotope; Image; Investigation; Investigational Drugs; Investigational New Drug Application; Label; Malignant - descriptor; Nerve Tissue; Neuroblastoma; Neurons; Norepinephrine; Organ; Outcome; Patients; Photons; Positron-Emission Tomography; Primary Neoplasm; Radiation; Radiation therapy; Radioactive Iodine; Radioisotopes; Radiometry; Radionuclide therapy; Recurrent disease; Research Project Grants; Resistance; Retrieval; Safety; Schedule; Scheme; Software Tools; Solid Neoplasm; Specificity; Staging; Testing; Therapeutic; Time; Toxic effect; Tracer; United States Food and Drug Administration; X-Ray Computed Tomography; advanced disease; conventional therapy; design; dosimetry; fluorodeoxyglucose positron emission tomography; high risk; imaging agent; imaging modality; in vivo; metaiodobenzylguanidine; mouse model; neoplastic cell; neuroblastoma cell; noradrenaline transporter; pediatric patients; pre-clinical; preclinical evaluation; preclinical study; radiosensitive; radiotracer; response; single photon emission computed tomography; software development; targeted agent; therapy outcome; tool; treatment effect; tumor; uptake

DESCRIPTION (provided by applicant): Neuroblastoma is the most common extracranial malignant solid tumor in children. Although the conventional treatment options are often curative at early stages, advanced disease remains fatal for a large percentage of patients, particularly for those who become resistant to conventional therapy. MIBG is taken up by sympathetic neurons via a specific norepinephrine transporter (NET) and 90% of all neuroblastoma tumors are MIBG-avid. Thus, when MIBG is labeled with 131I, a radionuclide that emits therapeutic beta particles with a relatively long physical half-life (8.02 days), 131I-MIBG becomes an agent for targeted radionuclide therapy of neuroblastoma. For the treatment with131I-MIBG, individualized radiation dosimetry can be achieved by pretherapy imaging using the same tracer with a different radioiodine such as I-123. I-123 is a favored imaging agent using gamma camera and SPECT; but it has a relatively shorter half-life than that of I-131 (13.2 hours versus 8.02 days) so that following the full time course of 123I-MIBG behavior in patients over a few days is not straightforward, and technically challenging. Instead, another radioiodine, I-124 has a closer half-life (4.2 days) to that of I-131, and can be imaged by PET that is considered quantitatively more accurate than SPECT. Our goals are to use 124I-MIBG PET/CT as an individualized 131I-MIBG radiotherapy prescription tool to achieve optimal treatment of tumors and minimal radiation dose to radiosensitive organs. Since 124I-MIBG has not been used in children for this indication (although 124I-MIBG was used in a limited number of adults), carefully designed preclinical studies with end points of radiation dose estimations should proceed before its human use. Our specific aims are: Aim 1: To determine the distribution of 124I-MIBG in tumors and normal organs in vivo using animal models of neuroblastoma. Small animal PET/CT with 124I-MIBG will be performed at multiple time points over four days, and the imaging data will be analyzed to study pharmacokinetics in tumors and other organs. Aim 2: To calculate the pediatric human-equivalent effective radiation dose in the range of patient sizes from preclinical 124I-MIBG imaging data. For this aim, our goal is to estimate the normal organ doses with 124I-MIBG to ensure safety, not specifically intended for 131I-MIBG treatment prescription. We will apply for the IND, and will prepare for human imaging as a part of this aim. Aim 3: To assess the feasibility of tumor and organ dosimetry with pediatric 124I-MIBG PET/CT in selected neuroblastoma patients who are scheduled for 131I-MIBG treatment. We will develop a patient-specific dosimetry calculation tool that will be available for the dose prescription of 131I-MIBG. Estimations of radiation dose will be focused on the determination of optimal activity needed to effectively deliver therapeutic dose to tumor cells while keeping radiation dose to normal organs at an acceptable level. The outcomes of the individualized prescription of the 131I-MIBG treatment will be descriptively compared to the therapy outcomes, particularly the primary tumor size reduction.

描述（由申请人提供）：神经母细胞瘤是儿童最常见的颅外恶性实体瘤。虽然传统的治疗方案通常在早期阶段是治愈性的，但晚期疾病对很大比例的患者仍然是致命的，特别是对那些对传统治疗产生耐药性的患者。MIBG通过特定的去甲肾上腺素转运蛋白（NET）被交感神经元摄取，90%的神经母细胞瘤肿瘤都是MIBG-亲嗜性的。因此，当MIBG用131 I（一种放射性核素，其发射具有相对长的物理半衰期（8.02天）的治疗性β粒子）标记时，131 I-MIBG成为用于神经母细胞瘤的靶向放射性核素治疗的药剂。对于131 I-MIBG治疗，可通过使用不同放射性碘（如I-123）的相同示踪剂进行治疗前成像来实现个体化辐射剂量测定。I-123是使用伽马照相机和SPECT的优选成像剂;但它的半衰期比I-131的半衰期相对较短（13.2小时对8.02天），因此在几天内跟踪患者中123 I-MIBG行为的全时程并不简单，并且在技术上具有挑战性。相反，另一种放射性碘，I-124具有与I-131更接近的半衰期（4.2天），并且可以通过PET成像，其被认为在定量上比SPECT更准确。我们的目标是使用124 I-MIBG PET/CT作为个体化131 I-MIBG放射治疗处方工具，以实现肿瘤的最佳治疗和对放射敏感器官的最小辐射剂量。由于124 I-MIBG尚未用于儿童的该适应症（尽管124 I-MIBG用于有限数量的成人），因此应在人体使用前进行精心设计的临床前研究，并进行辐射剂量估计终点。目的1：利用神经母细胞瘤动物模型研究124 I-MIBG在肿瘤和正常器官中的分布。将在4天内的多个时间点使用124 I-MIBG进行小动物PET/CT，并分析成像数据以研究肿瘤和其他器官中的药代动力学。目的2：根据临床前124 I-MIBG成像数据计算患者体型范围内的儿科人体等效有效辐射剂量。为此，我们的目标是估计124 I-MIBG的正常器官剂量，以确保安全性，而不是专门用于131 I-MIBG治疗处方。我们将申请IND，并将为人类成像做准备，作为这一目标的一部分。目标三：评估在计划接受131 I-MIBG治疗的选定神经母细胞瘤患者中使用儿科124 I-MIBG PET/CT进行肿瘤和器官剂量测定的可行性。我们将开发一个患者特定的剂量计算工具，可用于131 I-MIBG的剂量处方。辐射剂量的估计将集中在确定有效地向肿瘤细胞提供治疗剂量所需的最佳活性，同时将正常器官的辐射剂量保持在可接受的水平。将131 I-MIBG治疗的个体化处方的结局与治疗结局进行对比，特别是原发性肿瘤尺寸缩小。

项目成果

Exploration of PET and MRI radiomic features for decoding breast cancer phenotypes and prognosis.

• DOI: 10.1038/s41523-018-0078-2
• 发表时间: 2018
• 期刊: NPJ breast cancer
• 影响因子: 5.9
• 作者: Huang SY;Franc BL;Harnish RJ;Liu G;Mitra D;Copeland TP;Arasu VA;Kornak J;Jones EF;Behr SC;Hylton NM;Price ER;Esserman L;Seo Y
• 通讯作者: Seo Y

The Effect of Magnetic Field on Positron Range and Spatial Resolution in an Integrated Whole-Body Time-Of-Flight PET/MRI System.

磁场对集成全身飞行时间 PET/MRI 系统中正电子范围和空间分辨率的影响。

• DOI: 10.1109/nssmic.2014.7431006
• 发表时间: 2014
• 期刊: IEEE Nuclear Science Symposium conference record. Nuclear Science Symposium
• 作者: Huang,Shih-Ying;Savic,Dragana;Yang,Jaewon;Shrestha,Uttam;Seo,Youngho
• 通讯作者: Seo,Youngho