286 chapter 3 [18F]FDG PET/CT PET/CT is a 3D functional imaging technique that in vivo localises and quantifies positron-emitting isotopes such as fluorine-18. PET imaging with the non-metabolisable glucose analogue [18F]FDG reflects glucose metabolism [314]. After intravenous injection, [18F]FDG is, like D-glucose, taken up in eucaryotic cells by the membrane-bound sodium-dependent glucose transporters’ (GLUT) family. In the cytosol it is phosphorylated to [18F]FDG-6-phosphate by members of the hexokinase family. As phosphoglucose isomerase, the enzyme responsible for the second step in the glycolytic pathway, does not interact with deoxyglucose, [18F]FDG cannot be degraded further. Moreover, as most mammalian cells lack the enzyme to dephosphorylate [18F]FDG-6-phosphate, it accumulates in the cells, the rate dependent on perfusion, GLUT-capacity and hexokinase activity. Many pathological conditions cause regional alterations in glucose metabolism in tissues, through which [18F]FDG PET/ CT is an important tool in detection and staging of cancer and active inflammations. [18F]PET/CT is an imaging technique using ionising radiation with high sensitivity, but limited specificity due to other causes of [18F]FDG-uptake: coincidental findings may lead to further invasive diagnostics. [18F]FDG PET/CT is an important source of thyroid incidentalomas (i.e., unexpected incidental findings during an [18F]FDG PET/CT for other indications), with a pooled incidence of around 2.5% [450] and a rate of malignancy of around 30% [451]. These incidentalomas require additional workup by FNAC when their diameter exceeds 1 cm [452]. [18F]FDG PET/CT has a limited role in the management of thyroid cancer. Only when radioiodine refractory disease is suspected, [18F]FDG PET/CT plays an important role in disease monitoring [17]. In radioiodine refractory disease, differentiated thyroid carcinomas lost the capacity to concentrate radioiodine, but still have measurable thyroglobulin serum values as sign of vital residual disease. [18F]FDG PET/CT is also utilised for the initial staging of poorly differentiated or invasive Hürthle cell carcinoma. Similarly, [18F]FDG PET/CT plays an important role in staging of undifferentiated forms of thyroid cancer such as anaplastic thyroid cancer. [18F]FDG PET/CT is mentioned but not routinely advised in the current ATA guidelines for the management of thyroid nodules with indeterminate cytology, despite a growing body of evidence. The first prospective study by Kresnik et al. dates from 2003 and evaluated the usefulness of [18F]FDG PET/CT in the preoperative assessment of 43 suspicious thyroid nodules with suggestive cytologic results (pre-Bethesda) [453]. They found that thyroid carcinomas, in contrast to most benign thyroid nodules, demonstrate significantly increased glucose metabolism; at a cut-off value of the SUV of 2 g/mL, a 100% sensitivity, 63% specificity, and 100% negative predictive value was reached. However, the study Kresnik et al. did not represent the general population, because the study was performed in an area of endemic goiter and patients with papillary carcinoma were selected as positive control group. Subsequently, De Geus-Oei et al. investigated [18F]FDG PET/CT in 44 patients
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