Due to the low cellular density of lung parenchyma, overall glucose metabolism in the lungs is low. In combination with CT, tracer uptake due to inflammatory changes can be differentiated from malignant lung lesions in most cases.

In 0.15 % of all PET/CT examinations, intense focal tracer uptake in the lung can be observed that is not related to a pulmonary mass but rather a pulmonary vessel. As these findings are not detectable on follow-up scans, most authors believe that these lesions represent pulmonal microembolism: During radioactive tracer injection via an intravenous line, a small thrombus at the intravenous end of the intravenous line is loaded with a high concentration of ¹⁸F-FDG during tracer injection, dissoluted and finally stopped in the pulmonary capillaries (Hany et al. 2003; Chondrogiannis et al. 2015). Even if this finding does not demand any further investigation, the CT and the PET datasets have to be checked for misregistration to exclude malignancy.

The thymus is located in the upper ventral mediastinum and harbors an important role in lymphocyte development. While it can be clearly visualized in pediatric patients, the volume of the organ reduces over time and is rarely visible in the adult population. In accordance with organ volume, the ¹⁸F-FDG uptake decreases over time (Brink et al. 2001; Nakahara et al. 2001). In patients after chemotherapy or radioactive iodine ablation, however, an enlargement of the thymus and an increased tracer uptake, the so-called thymus rebound, can be sometimes observed and should not be mistaken for metastases or lymphoma (Cohen et al. 1980; Jeon et al. 2014, see Fig. 4).

In the regular, nonfasting state, the heart mainly metabolizes carbohydrates, while fasting leads to an increased consumption of fatty acids. As the myocardial layer of the left ventricle is thicker than in the other cavities of the heart, the strongest metabolic activity can be observed here in nonfasting patients. Therefore, the preparation of the patient is highly dependent on the clinical indication. To improve the detection of small tracer avid lesions in oncological patients, it is mandatory that patients fast for at least 4 h prior to ¹⁸F-FDG injection. Longer fasting times might be necessary when a lesion is closely related to the myocardium due to the high variability of cardiac glucose consumption (Boellaard et al. 2015).

This high variability can lead to multiple appearances of the heart in ¹⁸F-FDG PET, ranging from absent to a diffusely increased ¹⁸F-FDG uptake pattern. Furthermore, focal tracer uptake in the papillary muscles as well as regional tracer uptake, most notably in the lateroposterior and in the anterobasal region, is frequent. In patients with coronary artery disease, however, this regional uptake can be altered due to increased glucose consumption of hibernating myocardium (Mäki et al. 1996; Maurer et al. 2011).

In patients with atrial fibrillation, an increased uptake in the atrial wall can be observed that can be mistaken for mediastinal lymph nodes without careful analysis of the fused PET/CT images (Dong et al. 2014, see Fig. 5).

Rare cases of diffuse tracer uptake are inflammatory diseases such as pericarditis, myocarditis, and epicarditis as well as sarcoidosis, but its relevance in oncological PET imaging has to be evaluated further (James et al. 2011).

Albeit extraordinarily rare, benign as well as malignant cardiac masses can lead to an increased focal tracer accumulation, although a high SUVmax is a strong predictor of malignancy (Nensa et al. 2015). A far more frequent explanation for focal tracer accumulation than a malignant process is lipomatous hypertrophy of the interatrial septum, which is found in up to 2.2 % in CT imaging (Heyer et al. 2003). Albeit not a focal tumor, the increased fatty deposition in the intraatrial septum can show a markedly increase glucose uptake in ¹⁸F-FDG PET (Fan et al. 2005; Kuester et al. 2005, see Fig. 6).

Tracer uptake in the esophagus can be frequently observed, most notably in the gastroesophageal junction. Apart from increased smooth muscle activity, the prevalence of esophagitis seems to be the most common cause (Wu et al. 2014). Due to its focal appearance, it can be easily mistaken for a carcinoma of the esophageal junction. Without a morphological correlate, increased tracer uptake at this location is not a predictor of malignancy (see Fig. 7). The combination of a high SUVmax with a soft tissue mass or focal esophageal wall thickening, however, has to be considered a strong predictor of malignancy (Heusner et al. 2009; Stagg et al. 2014).

Gastrointestinal uptake in the stomach and the bowel is frequently observed in a multitude of different shapes and can be caused by many different reasons. Patchy, segmental, or diffuse tracer enhancement without a morphological correlate originates from ¹⁸F-FDG uptake of smooth muscle cells or the mucosa as well as intestinal microorganisms. Especially lymphoid tissue in the cecum can also exhibit a markedly increased tracer uptake (Rosenbaum et al. 2006). Furthermore, inflammatory lesions, for example, in patients with inflammatory bowel disease or patients with gastritis, can show a markedly increased tracer uptake. Special caution is necessary in patients with type 2 diabetes that are treated with metformin, an oral biguanide. Metformin increases glucose consumption in the gastrointestinal tract and leads to a markedly increased, segmental and continuous tracer uptake in the colon and, to a lesser extent, in the small intestine (Bailey 1995; Gontier et al. 2007, see Fig. 8). Although this effect can be reduced by stopping metformin intake 2–3 days prior ¹⁸F-FDG PET examinations, no definite recommendations are available concerning ¹⁸F-FDG administration and metformin intake (Özülker et al. 2010; Oh et al. 2010; Boellaard et al. 2015).

Focal tracer uptake in the colon, however, is observed in 1–3 % and associated with a high risk of a malignant or premalignant lesion and demands further colonoscopic evaluation (Kamel et al. 2004; Israel et al. 2005). Still, it has to be kept in mind that although focal tracer uptake in PET/CT has a specificity of 80.2 % for the detection of a colonic pathology, the sensitivity is only 14.8 %. Therefore, the presence of colonic pathologies does not have to coincide with focal tracer uptake (Shim et al. 2012; Keyzer et al. 2015).

In the kidneys, a strong tracer uptake of ¹⁸F-FDG can be regularly observed as sugars are excreted due to glomerular filtration. In contrast to glucose, however, the radioactive-labeled tracer is not reabsorbed in the tubuli, leading to a markedly increased tracer accumulation in the urinary tract (Rosenbaum et al. 2006). Sometimes, the radioactive urine causes nodal enhancement along the ureter imitating tracer avid lymph nodes on the PET images. In combination with the morphological CT images, the tracer accumulation can be normally clearly attributed to the ureter. Still, the intense tracer accumulation in the bladder caused by the radioactive urine might obscure adjacent lymph nodes.

In premenopausal female patients, physiological uptake in the uterus and the ovaries is highly dependent on the menstrual cycle. Especially in the ovulatory phase, a markedly increased ¹⁸F-FDG uptake can be observed in the ovaries and the endometrium. Additionally, a strong tracer uptake can be observed in the endometrium during early menstrual flow (see Fig. 9), while no increased tracer uptake is noted in the ovaries at this time. Therefore, it might be advisable to perform ¹⁸F-FDG a week before or shortly after menses to exclude physiological tracer uptake if a gynecological malignancy is suspected (Lerman et al. 2004; Nishizawa et al. 2004).

In patients with cervical cancer, an increased endometrial tracer uptake can be observed. However, this is not an indicator of endometrial invasion but is rather induced by local cytokines excreted by the tumor or increased uterine fluid collections caused by a consecutive cervical stenosis. Therefore, PET does not seem to improve the detection of endometrial invasion (Lerman et al. 2004).

In postmenopausal women, physiological tracer uptake in the uterus and the ovaries is rarely observed. In contrast to the glandular tissue in the breast, hormone replacement therapy does not seem to lead to an increased tracer uptake in the ovaries or in the endometrium. Hence, especially increased tracer uptake in the ovaries in postmenopausal women can indicate a malignant process and deserves further investigation (Lerman et al. 2004; Rosenbaum et al. 2006). Despite the high overall sensitivity of ¹⁸F-FDG PET for ovarian cancer, only a moderate tracer uptake can be frequently observed in premalignant lesions or early stage cancers. Still, a moderate tracer uptake in the ovaries can also be caused by benign lesions such as endometriomas (Fenchel et al. 2002). Therefore, a close comparison with the morphological images is warranted here.

Incidental tracer uptake in the prostate is detected in about 2 % of all PET/CT studies and is caused by prostate cancer in 17 %. Lesion localization in the peripheral zone and increased patient age seem to be predictors of malignancy, while an association with increased SUVmax is questionable (Bertagna et al. 2015). Still, the positive predictive value for incidental prostate uptake is low as tracer uptake in benign prostatic disease such as prostatitis or benign prostate hyperplasia is common. As the mortality of prostate cancer is low, discretion should be advised when applying invasive techniques to investigate incidental prostatic uptake, especially in oncological patients with a limited life expectancy (Reesink et al. 2015, see Fig. 10).

¹⁸F-FDG accumulation of the testes is age dependent. While a positive correlation between tracer uptake and patient age can be observed in pediatric patients, glucose metabolism decreases in aging male patients (Kitajima et al. 2007; Goethals et al. 2009). Asymmetrical tracer uptake, however, demands further evaluation as solitary metastases to the testes, or extranodal involvement in lymphoma patients have been reported (Weng and Schöder 2004; Sidhu et al. 2014).

Incidental increased tracer uptake in the skin is most frequently caused by inflammation. Especially focal inflammation, e.g., in infected atheroma or acne, can show an increased tracer uptake due to the increased presence of lymphatic cells. Apart from bacterial infections, viral infections such as an active herpes zoster infection can lead to an increased cutaneous tracer uptake that might even involve the associated lymph nodes (Wadih et al. 2015).

A rare inflammatory disease is hidradenitis suppurativa involving the hair follicles that can be predominantly found in the inguinal, perianal, and axillary region (see Fig. 14). Here, an intense tracer accumulation can be discovered involving the cutaneous tissue and the subcutaneous fat and can lead to fistulas and even osteomyelitis as well as malignant transformation (Simpson et al. 2011; Poh and Wong 2014). In most of the cases, diagnostic security can be increased by mere inspection which should therefore not be omitted.

Apart from the predominant white adipose tissue, brown adipose tissue can be found especially in young female patients and children. In contrast to white adipose tissue, which its primary ability is fat deposition, brown adipose tissue can generate warmth by the metabolization of triglycerides and sugars, especially in cold environments. If these patients are not kept warm during the uptake phase and the PET scan, symmetrical tracer uptake can be observed most frequently in the head and neck area but also in the mediastinum and the perivertebral fatty tissue. Although brown adipose tissue can be correctly identified on fused PET/CT images by the pattern of distribution and identification of fat as morphological correlate of focal tracer uptake, small tracer avid lesions that are also situated in the fatty tissue, such as lymph node metastases, can be obscured. Therefore, it can be advisory to prepare patients with known high activity of brown adipose tissue by keeping the patients warm after ¹⁸F-FDG injection (Boellaard et al. 2015). Furthermore, pharmacological means to decrease the glucose uptake in brown adipose tissue have been explored, for example, by administering propanolol or diazepam prior to tracer injection (Söderlund et al. 2007; Rakheja et al. 2011, see Fig. 15).

A rare variant is hibernoma, a benign tumor consisting of brown adipose tissue (Furlong et al. 2001, see Fig. 16). While the tumor mimics a lipoma in morphological imaging, it exhibits an extraordinary high tracer uptake in PET imaging. Although hibernomas neither do show signs of tumor invasion of the surrounding tissues nor solid components, it still cannot be differentiated from highly differentiated liposarcoma in morphological imaging. A possible tool of differentiation is a repeated PET imaging as strong SUV fluctuations of hibernomas have been observed in small cohorts (Smith et al. 2008). Still, histopathological correlation is necessary for a definite diagnosis.

Tracer uptake in the breast is observed in the glandular mammary tissue and can therefore be mainly observed in premenopausal women and postmenopausal women undergoing hormone replacement therapy. Intense tracer uptake of both breasts is frequently found in lactating women (see Fig. 17) but can also be asymmetrical if the child is predominantly fed from one side (Abhyankar et al. 2012). Therefore, especially small lesions can be obscured by the increased glandular uptake and can be difficult to detect in the PET dataset. Focal ¹⁸F-FDG uptake in the breast, however, is a strong predictor of malignancy and demands further investigation (Bertagna et al. 2015).