Non-invasive MRS in new anticancer drug development.
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.
Workman
P
P
CRC Department of Medical Oncology, University of Glasgow, UK.
Maxwell
R J
RJ
Griffiths
J R
JR
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002699:Chlorambucil / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism
D000970:Antineoplastic Agents; C031843:fluoromisonidazole; C049002:3,3-difluorochlorambucil; D002699:Chlorambucil; D008920:Misonidazole