Analysis of Temporally Varying Data. Chapter 6

Pharmacokinetics is a general term describing the uptake, metabolism and excretion of substances administered to a living organism. A complete description of the pharmacokinetics of a drug may include a vast number of physical, chemical and biological processes and can be very complex in its nature. In contrast to most pharmaceutical therapies, radiopharmaceutical therapy (RPT) often offers the opportunity to follow the pattern of changes in the pharmaceutical distribution over time in a patient's body due to radioactive emissions of the RPT agents and the relatively long physical half‑lives of the radionuclides used. By imaging these emissions, information about the pharmacokinetics of the RPT agent, critically important for personalized dosimetry calculations, can be obtained. Therapeutic radiopharmaceuticals are often administered intravenously, although oral, intra‑cavity, and intra‑arterial administrations are also employed. Upon entrance to the bloodstream and circulation, the radiopharmaceutical is transported across microvascular endothelia mainly driven by passive processes such as convection and diffusion. The rate of transport varies between tissues and depends on the capillary permeability and other factors such as the hydrostatic and colloid‑osmotic pressure [6.1]. The uptake of the radiopharmaceutical in tumour cells is often associated with active processes, mediated by membrane proteins such as symporters, receptors or antigens present on the cell surface [6.2]. Several studies have demonstrated that the uptake and effective half‑lives of radiopharmaceutical washout [6.3–6.7] in normal organs and tumours exhibit a large inter‑patient variation [6.8]. Additionally, large intra‑patient variations in tumour uptake have been observed [6.8]. These observations provide a strong argument for personalized dosimetry, clearly indicating that RTP pharmacokinetics needs to be determined for each individual patient and each organ and region of interest (ROI) (Chapter 1, Figs 1.3 and 1.4). The rate constants may also be of interest in themselves as they carry information about the turnover of the radiopharmaceutical in tissues.