Drug Distribution

Knowledge of the drug distribution in the body is important for assessment of possible desired or undesired interactions in various tissues. This type of information is not readily attained in humans, and except for PET studies, has to be derived indirectly from mathematical models with input from plasma pharmacoki-netics and extrapolation from animal data. These extrapolations are mostly uncertain because factors like distribution, plasma protein binding, metabolism in different organs and binding to receptors and enzymes are often markedly different between species as well as between different individuals of the same species. Significant changes in all modulating factors on drug distribution may occur in the disease or after pharmacological treatment with drugs. PET gives opportunities to measure tissue radioactivity and correlate it with drug concentration, allowing the observation of temporal changes with high accuracy and precision.

Studies of the deposition of inhaled compounds in humans have so far mainly been made with singlephoton scintigraphy. A strength of this method is that the majority of the respiratory system can be monitored simultaneously due to the large field of view of the gamma camera. There are a number of limitations in this method which makes PET a strong alternative. (see also chapter 22) PET, using the labeled active component, allows its deposition and disposition to be monitored [36]. Some compounds experience a rapid disposition, for example, from the oral cavity to the stomach or from lung parenchyma to blood. These studies are performed with the administration of very low amounts of radioactivity, 5-20 MBq, thereby reducing the radiation dose.

The use of 11C-labeled compounds in this context is advantageous since several PET studies can be performed on the same subject on the same day; for example, before and after a drug challenge.

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