Application of positron emission tomography in drug development

Positron Emission Tomography (PET) is a clinically established noninvasive imaging modality [1]. In PET, targeting ligands, or drug molecules labeled with a positron-emitting isotope, typically known as PET-radiopharmaceuticals, are introduced in to the body at a very low concentration (nanomolar or picomolar range), and are not intended to have any pharmacological effect. As the radioisotope decays, it emits a positron that interacts with an electron. This encounter produces a pair of high-energy (511 keV) gamma photons that move in nearly opposite directions. A circular array of detectors captures these photons and determines their source along a straight line of coincidence. These coincidences are forwarded to the image processing unit to generate PET images via mathematical reconstruction procedures (Figure 1). Commonly used PET radioisotopes (18F, 11C, 13N, 15O etc.) in clinical and developmental research are very short-lived and cyclotron-produced. The drug development process is very complex, time-consuming, and costly. The process for bringing a new molecular entity from preclinical discovery to market may take up to 15 years with a cost that may exceed $800 million [2]. Considering the current high failure rat