1H NMR STUDIES OF NON-HODGKINS LYMPHOMA

非霍奇金淋巴瘤的 1H NMR 研究

• 批准号: 7229582
• 负责人: JERRY D GLICKSON
• 金额: $ 35.61万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7229582
• 关键词: Address; Adriamycin PFS; Affect; Age; Algorithms; Analysis of Variance; Animal Model; Animals; Applications Grants; Biochemical; Blood; Bolero; Brain Neoplasms; Breast Carcinoma; Cancer Etiology; Cell membrane; Cells; Cessation of life; Chemotherapy-Oncologic Procedure; Choline; Clinic; Clinical; Clinical Research; Combination Chemotherapy; Computer software; Condition; Cyclophosphamide; Cytotoxic agent; Data; Deoxyglucose; Detection; Development; Diagnosis; Diffuse Large-Cell Lymphoma; Diffuse Lymphoma; Diffusion weighted imaging; Disease; Disease regression; Early Diagnosis; Enzymes; Exhibits; Future; Genes; Goals; Growth; Head and Neck Cancer; Heterogeneity; Hour; Human; Hybrids; Image; Imaging technology; Immunotherapy; Individual; International Prognostic Index; Investigation; Kyocristine; Label; Laboratories; Lactic acid; Large-Cell Lymphomas; Lesion; Lipids; Literature; MCF7 cell; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Mammary Neoplasms; Measurement; Measures; Methods; Microspheres; Modality; Modeling; Monitor; Multi-Drug Resistance; Mus; NMR Spectroscopy; Necrosis; Neuro-Oncological Ventral Antigen 2; Non-Hodgkin' s Lymphoma; Numbers; Patients; Perfusion; Pharmaceutical Preparations; Phospholipid Metabolism; Physiologic pulse; Physiological; Positron-Emission Tomography; Prednisone/Vincristine; Procedures; Production; Progressive Disease; Protocols documentation; Pulse taking; Purpose; Radiation; Radiation therapy; Rattus; Research; Research Personnel; Resolution; SCID Mice; Slice; Staging; Standards of Weights and Measures; Techniques; Testing; Therapeutic; Therapeutic Index; Time; Translating; Tumor Volume; United States; United States National Institutes of Health; Weight; Writing; Xenograft Model; Xenograft procedure; aminopropylphosphonate; base; bryostatin; cancer therapy; chemotherapy; computer program; detector; dimethyl methylphosphonate; experience; extracellular; fibrosarcoma; improved; indexing; male; partial response; prognostic; programs; prototype; quantum; research study; response; rituximab; sarcoma; spectroscopic imaging; tumor; tumor growth; tumor xenograft

DESCRIPTION (provided by applicant): This is a proposal to develop and refine 1H NMR spectroscopy and imaging technology for the prediction and early detection of the response of non-Hodgkin's lymphoma (NHL) to chemotherapy, immunotherapy and radiation therapy. The study will be performed on a xenograft model of human diffuse large cell lymphoma WSU-DLCL2 in SCID mice. This model will be used to develop and test pulse sequences, evaluate their sensitivity for detection of response to chemotherapy, immunotherapy and radiation therapy and to examine the biochemical and physiological mechanisms underlying therapy induced spectroscopic and imaging changes. A selective multi-quantum coherence transfer pulse sequence, SeI-MQC, for detection of lactate (Lac) and total choline (TCho) will be hybridized with a Hadamard slice selection pulse sequence, and software for implementation of the hybrid Had-SeI-MQC sequence on Varian ANOVA will be written. Standard MRI pulse sequences for implementing dynamic contrast enhanced (DCE), diffusion weighted imaging (DWI), T2 weighted imaging (T2WI) and Tip_weighted imaging (Tlp) on the Varian will be streamlined so that a complete examination consisting of MS-BASSALE or Had-SeI-MQC combined with DCE, DWI, T2WI and Tlp (or a subset of these imaging sequences) can be implemented on the NHL model within one hour. This animal study will serve as the basis for clinical implementation of this protocol that will be submitted as a future proposal to the NIH. This program builds on previous research on murine tumor models which has demonstrated that decreases in the Lac resonance of tumors provide an early and sensitive indicator of tumor response to chemotherapy and radiation therapy. In addition, a multicenter clinical 31P MRS study of NHL patients in which this laboratory is participating has demonstrated that the (PC+PE)/NTP ratio measured prior to initiation of therapy together with the International Prognostic Index (a clinically based assessment index for NHL) can predict which tumors will exhibit a complete clinical response (CR) as opposed to a partial response (PR) or progressive disease (PD). It is hypothesized that 1H MRS measurements of TCho will provide the same prognostic information at much higher spatial/temporal resolution and that inclusion of response sensitive MRI data will further improve on the predictive capacity of this method. However, the present study of the animal model of NHL will only evaluate the capability of these methods to detect therapeutic response at an early stage.

描述（由申请人提供）： 这是一项开发和完善1H NMR光谱和成像技术的建议，用于预测和早期检测非霍奇金淋巴瘤（NHL）对化疗，免疫治疗和放射治疗的反应。本研究将在SCID小鼠的人弥漫性大细胞淋巴瘤WSU-DLCL 2异种移植模型中进行。该模型将用于开发和测试脉冲序列，评估其检测对化疗，免疫治疗和放射治疗的反应的灵敏度，并检查治疗引起的光谱和成像变化的生化和生理机制。将用于检测乳酸盐（Lac）和总胆碱（TCho）的选择性多量子相干转移脉冲序列SeI-MQC与Hadamard切片选择脉冲序列杂交，并编写用于在Varian ANOVA上实施混合Had-SeI-MQC序列的软件。将简化用于在Varian上执行动态对比增强（DCE）、弥散加权成像（DWI）、T2加权成像（T2 WI）和Tip_weighted成像（Tlp）的标准MRI脉冲序列，以便在1小时内在NHL模型上执行由MS-BASSALE或Had-SeI-MQC结合DCE、DWI、T2 WI和Tlp（或这些成像序列的子集）组成的完整检查。本动物研究将作为本方案临床实施的基础，并将作为未来提案提交给NIH。 该计划建立在先前对小鼠肿瘤模型的研究基础上，该研究已经证明肿瘤的Lac共振的降低提供了肿瘤对化疗和放疗反应的早期和敏感的指标。此外，该实验室参与的NHL患者的多中心临床31 P MRS研究表明，在开始治疗前测量的（PC+PE）/NTP比值与国际预后指数（NHL的临床评估指数）可以预测哪些肿瘤将显示完全临床缓解（CR），而不是部分缓解（PR）或疾病进展（PD）。假设TCho的1H MRS测量将以更高的空间/时间分辨率提供相同的预后信息，并且包含响应敏感的MRI数据将进一步提高该方法的预测能力。然而，目前NHL动物模型的研究仅评估这些方法在早期阶段检测治疗反应的能力。