Premium
Non‐invasive MRS in new anticancer drug development
Author(s) -
Workman Paul,
Maxwell Ross J.,
Griffiths John R.
Publication year - 1992
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1940050513
Subject(s) - misonidazole , chlorambucil , drug , pharmacology , pharmacokinetics , drug development , pharmacodynamics , anticancer drug , chemistry , medicine , chemotherapy , in vitro , biochemistry , cyclophosphamide
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 β,β‐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 β,β‐difluorochlorambucil; but fluoromisonidazole was shown to accumulate in tumours and shows promise as a chemical probe for tumour hypoxia, detectable by 19 F MRS.