NMR 代谢和生理标志物的治疗反应。

NMR metabolic and physiological markers of therapeutic response.

机构信息

Laboratory of Molecular Imaging, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

出版信息

Adv Exp Med Biol. 2011;701:129-35. doi: 10.1007/978-1-4419-7756-4_18.

DOI:10.1007/978-1-4419-7756-4_18

PMID:21445779

Abstract

Identification of reliable metabolic and physiological NMR detectable markers for prediction and early detection of therapeutic response is essential to enabling NMR guided individualized therapy for cancer. Because non-Hodgkin's lymphoma (NHL) is a prevalent form of cancer that exhibits~50% response to therapy and often presents with large superficial lesions easily accessible to multinuclear magnetic resonance spectroscopy (MRS) measurements, it is an ideal test bed for development of NMR methods for prediction and early detection of response.A multicenter study, in which we have participated, has already shown that pre-treatment(31) PMRS measurement of the phosphate monoester (PME)to nucleoside triphosphate (NTP) ratio can identify about 2/3 of the patients who are destined not to exhibit a complete clinical response to a variety of therapeutic agents.Because (31)PMRS is limited to relatively large superficial tumors, we have been exploring (1)HMRS and MRI methods for early detection of therapeutic response. Using xenografts of the most common form of human NHL, diffuse large B-cell lymphoma (DLBCL), we have detected therapeutic response within one cycle of therapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), rituximab plus CHOP (RCHOP) or radiation (15 Gy) through detection of a decrease in lactic acid (Lac) or total choline (tCho) and an increase of apparent diffusion coefficients (ADC). We have also performed (1)H MRS of NHL patients in a clinical scanner. One of the patients exhibited a 70% decrease in Lac within 48 h of treatment with RCHOP.

摘要

鉴定可靠的代谢和生理 NMR 可检测标志物对于预测和早期检测治疗反应至关重要，这对于实现 NMR 指导的个体化癌症治疗至关重要。由于非霍奇金淋巴瘤（NHL）是一种常见的癌症形式，约有 50%的患者对治疗有反应，而且常常表现出易于接受多核磁共振波谱（MRS）测量的大型浅表病变，因此它是开发用于预测和早期检测反应的 NMR 方法的理想试验台。我们参与的一项多中心研究已经表明，治疗前（31）PMRS 测量磷酸单酯（PME）与核苷三磷酸（NTP）的比值可以识别出约 2/3 的患者，这些患者注定不会对各种治疗药物完全产生临床反应。由于（31）PMRS 仅限于相对较大的浅表肿瘤，我们一直在探索（1）HMRS 和 MRI 方法以早期检测治疗反应。使用最常见的人类 NHL 形式弥漫性大 B 细胞淋巴瘤（DLBCL）的异种移植物，我们通过检测乳酸（Lac）或总胆碱（tCho）的减少和表观扩散系数（ADC）的增加，在一个周期的 CHOP（环磷酰胺、多柔比星、长春新碱、泼尼松）、利妥昔单抗加 CHOP（RCHOP）或放疗（15Gy）内检测到治疗反应。我们还在临床扫描仪中对 NHL 患者进行了（1）H MRS 检查。其中一名患者在接受 RCHOP 治疗的 48 小时内 Lac 降低了 70%。