822 http://oncology.thelancet.com Vol 8 September 2007 Review Non-[¹⁸F]FDG PET in clinical oncology Ashley M Groves, Thida Win, Simona Ben Haim, Peter J Ell PET is an exquisitely sensitive molecular imaging technique using positron-emitting radioisotopes coupled to specific ligands. Many biological targets of great interest can be imaged with these radiolabelled ligands. This review describes the current status of non-18-fluorodeoxyglucose PET tracers that have a potential clinical effect in oncology. With the help of these tracers, knowledge is being acquired on the molecular characterisation of specific tumours, their biological signature, and postinterventional response. The potential role of these imaging probes for tumour detection and monitoring is progressively being recognised by clinical oncologists, biologists, and pharmacologists. Introduction PET is a highly sensitive (picomolar) method of molecular imaging that makes use of ligands labelled with positron-emitting isotopes. The most commonly used positron-emitting radionuclides include carbon-11 (¹¹C), oxygen-15 (¹⁵O), nitrogen-13 (¹³N), and fluorine-18 (¹⁸F). All these radionuclides are produced by a cyclotron but only one, ¹⁸F, can be transported from its production site, as a result of its longer half-life (2 h) compared with those of ¹¹C, ¹⁵O, and ¹³N (2–20 mins). Other positron- emitting radionuclides have longer half-lives (eg, iodine- 124 [¹²⁴I; 4 days] and copper-64 [⁶⁴Cu; 12 h]), which allow their remote distribution, or are available from the daily elution of generators on site (ie, gallium-68 [⁶⁸Ga] or rubidium-82 [⁸²Rb]). Once an appropriate target has been chosen for imaging, expertise is needed to identify a suitable radionuclide for labelling coupled to an appropriate homing ligand. 18-fluorodeoxyglucose ([¹⁸F]FDG) is the most widely used tracer in oncology. The clinical success attributed to the use of [¹⁸F]FDG-PET took time to establish. The production of [¹⁸F]FDG was reported by Ido in 1978, but the current method of synthesis used for this compound was published by Hamacher in 1986. 1 However, the US Food and Drug Administration did not approve the tracer as a radiopharmaceutical until 1997. Standard PET scanners have been developed and are now combined (hybridised) with sophisticated CT units to provide multimodality imaging via PET/CT. Although this imaging technique is now starting to be used in cardiology and neurology, the main indications for PET/CT remain in oncology. When [¹⁸F]FDG is injected into the body it is taken up into various tissues, where it becomes intracellularly trapped. Conventional wisdom informs that cancer cells over express glucose transporters, and, indeed, this glycolytic phenotype is present in most cancers. Increased glucose transport is associated with increased glycolysis of the cancer cell and an increase in hexokinase activity. Tissues that metabolise glucose faster will accumulate more [¹⁸F]FDG; therefore, the more metabolically active the cell, the more uptake of tracer. Hence, cancer cells can be differentiated from more benign tissues by their increased metabolism. This uptake can be semiquantified on PET by using the standardised uptake value (SUV), which takes into account the injected dose of tracer and is corrected for patient height and weight. Uniform distribution in the body would produce an SUV of 1 and the amount of uptake in a lesion can, in itself, be used to predict the likelihood of malignancy. These important biological and physical properties of [¹⁸F]FDG result in its continued use in oncology, despite the development of many other PET tracers. However, [¹⁸F]FDG is not a specific tracer and cannot differentiate between cells that have a high metabolic rate associated with neoplasia, and those where the increased metabolic rate is associated with other aetiologies—ie, infection, inflammation, or even normal physiological uptake such as in brown fat, granulomas, and organs. Moreover many malignancies do not exhibit high metabolic rates and, therefore, are poorly imaged by [¹⁸F]FDG—the prostate being a prime example. 2–4 Many biological targets can be imaged with radiolabelled ligands other than [¹⁸F]FDG. This review describes the current status of non-[¹⁸F]FDG PET tracers that have a potential clinical effect in oncology. Osteoblast metabolism 18-fluoride (figure 1) is taken up into hydoxyapatite crystals in bone to form the mineral fluoroapatite. Lancet Oncol 2007: 8: 822–30 Institute of Nuclear Medicine, University College London, London, UK (A M Groves FRCP, Prof S Ben Haim MD, Prof P J Ell FMedSci); Respiratory Medicine, Lister Hospital, Stevenage, UK (T Win MRCP) Correspondence to: Dr Ashley Groves, Institute of Nuclear Medicine, University College London, London NW1 2BU, UK drashleygroves@hotmail.com Figure 1: 18-fluoride-PET/CT examination of a female patient with breast cancer complaining of low back pain From left to right, coronal PET, sagittal CT, sagittal PET, and fused sagittal CT with PET images. Many areas of focal increased uptake of tracer can be seen, predominantly in the lumbar spine and pelvis, in keeping with metastatic disease. Sclerotic bone lesions are seen on the CT images in a similar distribution to those on the PET images.