Phenotype analysis, with for example, debrisoquine or sparteine should be avoided during on-going drug treatment as many drugs, especially psychotropics may inhibit CYP2D6 activity, leading to increased MRs. Genotyping may of course be performed independent of ongoing drug treatment. As pointed out above, interethnic differences must be considered when choosing which alleles are to be identified and when interpreting the genotype-phenotype relationship. With the development of new, less expensive and more rapid genotyping methods, the use of such techniques in drug development, academic research and clinical practice is expected to increase in the future. Today, genotyping methods are available for the identification of PM as well as of UM with CYP2D6 gene duplication/amplification. However, only about 40% of subjects with debrisoquine MRs of 0.1 or lower carry duplicated/multiduplicated genes, leaving about 60% of very rapid metabolizers unidentified by genotyping [23]. Efforts to find other molecular genetic explanations to ultrarapid metabolism in these subjects have so far been unsuccessful. The clinical usefulness of genotyping would be greatly increased if it would allow more accurate prediction of the catalytic activity (MR) within the EM phenotype.
A thorough assessment of the uPAR targeting agents reveals crucial differences in modalities, biodistributions, imaging windows, epitopes targeted, and production methods. Therefore, a one-size-fits-all solution to target all types of diseases where uPAR is involved is probably not feasible, like for most, if not all, molecular targets [5]. For instance, peptides may find their utility in more acute situations such as atherosclerosis imaging. Antibodies seem more ideal for abdominal imaging where the high non-specific background of kidneys can be a hindrance or in more elective settings where a large imaging window is desired. Not only will selecting an optimal agent be challenging, also designing and selecting preclinical animal models that take the species specificity of the imaging agents into account, since most tracers designed for clinical applications have high affinities for human uPAR but no or reduced affinities for mouse uPAR [201, 218, 226, 227].
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