Workman P, Maxwell R J, Griffiths J R
CRC Department of Medical Oncology, University of Glasgow, UK.
NMR Biomed. 1992 Sep-Oct;5(5):270-2. doi: 10.1002/nbm.1940050513.
In the rational development of anticancer drugs it is important to employ all the available pharmacological information. Early clinical trials provide an opportunity for hypothesis testing. MRS techniques have the potential to provide valuable data on the preclinical and clinical pharmacokinetics and pharmacodynamics of drugs non-invasively. Here we illustrate advantages and pitfalls of MRS using studies of two fluorine-containing cancer drugs: a beta,beta-difluoro analogue of the alkylating agent chlorambucil and a fluorinated derivative of the nitroimidazole misonidazole, Ro 07-0741. Limitations include signal quenching via protein binding and inadequate sensitivity for more potent drugs like beta,beta-difluorochlorambucil; but fluoromisonidazole was shown to accumulate in tumours and shows promise as a chemical probe for tumour hypoxia, detectable by 19F MRS.
在抗癌药物的合理研发中，利用所有可用的药理学信息非常重要。早期临床试验为假设检验提供了机会。磁共振波谱（MRS）技术有潜力以非侵入性方式提供有关药物临床前和临床药代动力学及药效学的有价值数据。在此，我们通过对两种含氟抗癌药物的研究来说明MRS的优点和缺陷：一种是烷基化剂苯丁酸氮芥的β,β-二氟类似物，以及硝基咪唑甲硝唑的氟化衍生物Ro 07-0741。局限性包括通过蛋白质结合导致的信号淬灭，以及对像β,β-二氟苯丁酸氮芥这样更强效药物的灵敏度不足；但氟代甲硝唑被证明可在肿瘤中蓄积，并有望作为一种用于检测肿瘤缺氧的化学探针，可通过19F MRS检测到。
