In PET (Positron Emission Tomography), radioligands and radiotracers contain isotopes which emit positrons upon nuclear decay. These positrons then annihilate in tissue to produce two nearly coincident high energy photons, which can be detected by a ring of detectors around the object (the PET scanner). Because both photons from an event are detected, PET uses electronic collimation and is thus more sensitive than SPECT (see below).

In microPET, the instrumentation is optimized for small animal studies and is thus usually of higher resolution.

Due to the low spatial resolution of PET images, PET is nowadays usually coupled to CT, or MRI, which afford higher resolution images for coregistration to provide spatial localization. 

The most common PET tracer is [18F]-FDG, an analog of glucose that is taken up into cells and phosphorylated in the same way as glucose, but cannot undergo any of the subsequent steps of glycolysis. As such, it accumulates in tissues proportionally to the rate of glycolysis and is mainly used in clinics for the detection of cancer throughout the body due to the Warburg effect; it can also be used in clinical trials to detect early effects of cancer therapy. [18F]-FDG is also used to measure glycolysis in the brain, and is a biomarker of several neurodegenerative diseases.

Preclinically [18F]-FDG is also used in rodents for measuring brain and tumour glycolysis in disease models and in response to therapy.

In addition to [18F]-FDG, a wide range of other molecules have been radiolabelled to create radiotracers or radioligands using other radionuclides  (e.g. Ga-68, C-11, O-18): these differ in radioactive half-life as well as the energy of the emitted positron. Typically small therapeutic molecules are labelled with C-11 and F-18 whilst larger biomolecules are labelled with Ga-68, Cu-64 and Zr-89.  O-18 is used to radiolabel water for perfusion assessment.

Major PET applications revolve around the determination of receptor densities or metabolic reaction rates for a wide number of receptors and biological processes as detailed in the radiotracers table (T. Jones & P. Price, “Development and experimental medicine applications of PET in oncology: a historical perspective”, https://doi.org/10.1016/s1470-2045(11)70183-8; T. Jones, E.A. Rabiner, “The development, past achievements, and future directions of brain PET”, https://doi.org/10.1038/jcbfm.2012.20 ). 

Importantly, radioligands can be used to assess the drug occupancy of therapeutics that bind to the same target as the PET tracer, which provides unique PK/PD information, especially in the brain (P.R. Matthews et al., “Positron emission tomography molecular imaging for drug development”, https://doi.org/10.1111/j.1365-2125.2011.04085.x).

In addition, longer-lived isotopes can be used to radiolabel a wide range of biotherapeutic compounds to allow the determination of biodistribution and tumour targeting in preclinical systems or in man (W. Wei et al., “ImmunoPET: Concept, Design, and Applications”, https://doi.org/10.1021/acs.chemrev.9b00738).

Finally, several PET tracers have been developed that are trapped by exogenously introduced genes, providing a reporter gene / theranostic imaging system that can be translated to man (C. Kitzberger et al., “The sodium iodide symporter (NIS) as theranostic gene: its emerging role in new imaging modalities and non-viral gene therapy”, https://doi.org/10.1186/s13550-022-00888-w).

Although PET is mostly widely used clinically and pre-clinically, it is also a powerful imaging tool for plant biologists. In fact, while current laboratory methods for the measurement of metabolic and transport processes in plants are destructive and allow monitoring only a very limited number of plants or sections of plants, PET allows to visualize non-invasively the metabolic and transport processes in the plant vascular systems and organs (S. Komarov & Y.C. Tai, “Positron Emission Tomography (PET) for Molecular Plant Imaging”, https://doi.org/10.1007/978-1-0716-2537-8_11).

PET/CT

Due to the relatively low resolution of PET, it is usually combined with a CT scanner, with PET-CT images acquired sequentially (in the same session) and co-registered to allow the PET signal to be localized. The CT data is also used to correct the PET image for attenuation.

PET radioisotopes, tracers and related example applications from the Nodes

To view the PET radioisotopes available, click here. Please contact info@eurobioimaging.eu if you cannot find what you are looking for on our website.