An excellent review of the role of MR in drug development was published this year in NMR in Biomedicine, and elegantly expounded upon at the recent 7th Conference of the ISMRM, Philadelphia. 1 The review discussed and presented detailed evidence of the current and potential contribution of NMR to the various steps of the drug development process. However, the description was limited almost exclusively to the MRI of pharmacodynamics, claiming that pharmacokinetics was "beyond the scope of MRS due to lack of sensitivity". For those not familiar with these terms, they may be defined simply as follows. Pharmacodynamics is what the drug does to the body, and pharmacokinetics, or PK, is what the body does to the drug. Thus, PK describes drug distribution, including uptake and/or activation of the drug in the target tissue, whether that be brain, heart, muscle or, for oncology, the tumour.
Measurement of the concentration of drugs and/or metabolites is important in at least two aspects of drug development. First, identification and validation of new targets demand measurement of drug concentrations in the target tissue. Conventionally, this can be achieved by whole tissue extraction (providing one time point per animal) or in the clinic via a biopsy, which in the case of oncology may yield non-representative data due to the well-known heterogeneity of solid tumours. MRS in vivo, however, can provide repeat real-time measurements providing important PK parameters such as rates of drug uptake and elimination, C max , and area-under-the-concentration-time-curve (AUC) and, where relevant, rates of conversion to anabolites and catabolites of the administered drug.
A second important aspect of drug development and indeed one where many drugs fail to progress, is in clinical evaluation during phases I-II, in which the optimum dose in an individual patient needs to be determined. These parameters are based upon the plasma AUCs of the drug as a surrogate for drug concentrations in the target tissue, and for the same dose can vary by at least three-fold due to wide inter-patient variation in drug absorption, distribution and elimination. 2 Thus noninvasive measurement in the target tissue would improve individualization of the dose schedule and aid pharmacokinetically guided dose escalation.