Potential of PET in oncology and radiotherapy

Abstract

Positron emission tomography (PET) is a non-invasive imaging technique based on coincidence detection of two simultaneously emitted photons that occurs when a positron annihilates after combination with an electron. Positrons are emitted from proton-rich unstable isotopes. Such short-lived radioactive isotopes are made in a cyclotron and then chemically linked to a probe molecule (e.g. a drug, water or a metabolite) to form a labelled PET tracer that is injected intravenously into a patient. Single emitted positrons combine with an electron to form a positronium, the lifetime of which is very short, resulting in annihilation of the positron and electron (all the mass is converted into electromagnetic radiation). To conserve energy and linear momentum, the electromagnetic radiation appears in the form of two photons of equal energy (511 keV; equal to the rest mass energy of the electron and positron), which are emitted at 180 to each other. The emitted photons are detected by a technique known as coincidence detection. A PET scanner comprises a large number of scintillation detectors; when two scintillation detectors that are separated by 180 are both stimulated simultaneously, they will transmit a coincident signal. This enables localisation of a source without the need for physical (lead) collimation. This fundamental physics forms the basis of dynamic detection and threedimensional localisation of the positron emitter and confers advantages of greater efficiency and resolution for PET over other nuclear imaging methods. Since a number of commonly occurring elements such as carbon, oxygen, nitrogen and fluorine have positron-emitting radionuclides, the stable nuclides of these elements can potentially be replaced by their positron-emitting counterparts in a number of compounds and evaluated using PET (Table 1). Emission of positrons from the compound follows the presence of such compounds when used as tracers of tissue function within the body; hence, PET can provide unique functional imaging data not available with other modalities. Moreover, the ability to correct for attenuation of radiation by body tissue as well as the highly sensitive nature of PET technology makes it possible for accurate quantification of the radiolabelled compound to picogram amounts. These properties of PET can be utilised to provide functional in vivo imaging data and as a result, the utility of PET has increased considerably over the last few years. The wide usage and worldwide acceptability of the radioligand fluorine-18-radiolabelled fluorodeoxyglucose (F-FDG) as a diagnostic PET imaging tool has made FDG-PET synonymous with PET. FDG follows the same route as glucose into cells, where it is phosphorylated by hexokinase to FDG-6-phosphate. Unlike glucose, little further metabolism occurs and FDG-6-phosphate remains essentially trapped within cells, with the rate of accumulation proportional to the rate of glucose utilisation. FDG-6-phosphate has low membrane permeability and although dephosphorylation does occur, it is very slow in brain, heart and tumour, which have very low levels of glucose-6-phosphatase. FDG uptake in tumours probably reflects a combination of factors, including phosphorylating activity of mitochondria, degree of hypoxia and levels of glucose transporters [1–3]. The role of FDG-PET for imaging and staging of malignant tumours is well established in oncology and is used in a routine clinical environment in many countries for diagnostic purposes. In addition to its diagnostic utility, other salient features of PET, notably its capability to image functional changes, make it a potential tool for further research in oncology. Therefore, a number of other PET probes in addition to FDG have been imaged and are being developed. The potential role of PET as a research tool in oncology can be broadly divided into five main areas: