Understanding the uptake of a drug by diseased tissue, and the drug's subsequent spatiotemporal distribution, are central factors in the development of effective targeted therapies. However, the interaction between the pathophysiology of diseased tissue and individual therapeutic agents can be complex, and can vary across tissue types and across subjects. Here, we show that the combination of mathematical modelling, of high-resolution optical imaging of intact and optically cleared tumour tissue from animal models, and of in vivo imaging of vascular perfusion predicts the heterogeneous uptake, by large tissue samples, of specific therapeutic agents, as well as their spatiotemporal distribution. In particular, by using murine models of colorectal cancer and glioma, we report and validate predictions of steady-state blood flow and intravascular and interstitial fluid pressure in tumours, of the spatially heterogeneous uptake of chelated gadolinium by tumours, and of the effect of a vascular disrupting agent on tumour vasculature.

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We have examined the anatomy of the pelvic (inferior hypogastric) plexus in six male cadavers, paying particular attention to gross anatomical landmarks that might aid in locating it and have used immunohistochemistry to study the small branches of the plexus that supply the prostate gland. The pelvic plexus was found two finger breadths lateral to the third anterior sacral foramina, lying deep to a line drawn from third sacral vertebra, the conventional level of the recto-sigmoid junction, and the palpable posterior superior surface of the pubic symphysis. Immunohistochemical staining showed small nerve branches from the pelvic plexus entering the prostate gland and the presence of ganglia within the prostate gland that contained both tyrosine hydroxylase positive and negative neuronal cell bodies. This information may be useful in nerve-sparing surgical procedures and in discussions of the functional implications of perturbations of prostate innervation.