FDG is a glucose analog and thus follows the similar fate as glucose in living tissues. Glucose enters the cell through glucose transporters, gets phosphorylated to glucose-6 phosphate by hexokinase, and further metabolism occurs (1). FDG, however, does not get metabolized further once it is phosphorylated to glucose-6 phosphate and is trapped inside the cell. FDG uptake inside the cells is dependent on glucose transporters, which indirectly get affected by serum glucose level, insulin level, and cellular demand (1).

The quantitative measurement of ¹⁸F-FDG accumulation in tissues has not yet been standardized (2). The commonly used parameter for quantitative measurement is the maximum standardized uptake value (SUVmax). Related quantitative parameters include, among others, the SUVpeak, SUVmean, total lesion glycolysis (TLG), and metabolic tumor volume (MTV) (2).

¹⁸F-FDG PET/CT plays a pivotal role in imaging malignant processes, and has been used to detect and evaluate both solid and haematological maligancies (3). FDG, as a glucose analog, adds a benefit of depicting functional information—hence metabolic abnormalities before anatomic changes occur (4). This is based on increased glucose uptake and increased glycolytic activity in malignant cells (3).

¹⁸F-FDG PET/CT is a very useful tool in the diagnosis and follow-up of malignant processes, due to the sensitivity of the tracer and imaging modality. It aids in upstaging and downstaging of the disease extent, which leads to a change in disease management (5). ¹⁸F-FDG PET/CT is useful in the detection of malignant disease with high sensitivity; it does, however, have the limitation of low specificity—in that a highly metabolically active lesion may be indicative of malignant, reactive, or reparative changes, and infective or inflammatory changes (1). To increase its specificity, it may be of importance to review the patient's clinical history, particularly oncologic history, such as treatment and procedures. This is in addition to other imaging modalities, together with laboratory changes (3). This clinical information may be in a prepared questionnaire or obtained in person. Despite these measures, there will be lesions with indeterminate uptake of tracer on ¹⁸F-FDG PET/CT (3).

The physiological biodistribution of FDG is the brain (gray matter), vocal cords, tonsils, thymus, skeletal muscle, brown fat, left ventricular myocardium, bowel, liver, spleen, kidneys, ureter, urinary bladder, and bone marrow (6). Physiological uptake in the gingival, genioglossus, and pterygoid muscles has also been described (7).

Various (musculoskeletal, infective, and inflammatory) processes that may be mistakenly interpreted as malignant changes will be discussed by way of a pictorial review below.

Cervical carcinoma is an AIDS-defining illness (9, 10). Immunocompromised women living with HIV with concomitant human papillomavirus infection have a higher chance of developing pre-invasive lesions, which lead to cervical carcinoma (8). ¹⁸F-FDG PET is of use in the diagnosis, staging, and detection of metastasis and in post-treatment monitoring of several AIDS-defining malignancies (11). However, caution should be taken, as immunosuppressed patients are also prone to infection. Sites of infection may mimic metastatic disease as in the case of the 38-year-old woman with a stage IIIB cervical carcinoma in aforementioned Figure 5. This is a clinical situation of an immunocompromised individual with retroviral disease on antiretroviral treatment. The psoas collection has radiological features of a cold abscess. Osseous infection may also mimick metastatic disease, as in this case of a 54 year old man with renal cell carcinoma. His combined FDG PET/CT images (Figure 6) showed an intense lesion in the left side of the mandible, which was due to osteomyelitis.

The major source of energy for skeletal muscles during the resting state is fatty acid oxidation (1). This results in homogeneous uptake of FDG in skeletal muscle. Plasma insulin, however, can increase glucose uptake in skeletal muscle by inducing the translocation of GLUT-4 from the intracellular vesicles to the plasma membrane and can thus result in increased skeletal glucose uptake in postprandial state (1). Voluntary and involuntary muscular activity can result in increased FDG uptake, which may result in a wide variety of seemingly pathological uptake.

Diffuse whole-body muscle uptake may be seen in patients with recent insulin injection, strenuous exercise involving strenuous muscle groups, and recent meal consumption (1).

Activities such as talking can cause increased uptake in bilateral vocal cords. Muscular uptake involving the upper extremities could result from activities that require the use of skeletal muscle such as turning pages of a book (1).

In individuals who experience muscle exertion, uptake may be seen in different parts of the body (Figure 7). In the same vein, in individuals with chronic obstructive pulmonary disease, due to difficult breathing and/or excessive coughing, intercostal muscular and diaphragmatic uptake may be seen.

Active inflammatory arthropathies because of psoriasis, rheumatoid arthritis, gout, and ankylosing spondylitis may mimic disease. The uptake of tracer in these conditions is dependent on the presence of synovitis (7). Figure 8 shows an ¹⁸F-FDG PET/CT study done on a 69-year-old woman with left breast carcinoma, which showed intense uptake in the gleno-humeral joints, with subchondral cystic osteodegenerative changes on CT.

A number of images (Figures 9–12) that represent multiple sites of intense FDG activity in the skeleton are displayed below. All changes were due to osteodegenerative changes.

In a study evaluating cervical, thoracic, and lumbar spine uptake in 150 patients who underwent ¹⁸F-FDG PET/CT scan, Costelloe et al. found abnormal uptake corresponding to osteodegenerative change in 22% of patients (7). They, however, found a weak correlation between severe osteodegenerative changes and the degree of uptake (7).

Metallic objects such as orthopedic hardware, dental implants, pacemakers, and injection ports attenuate photons, and the degree of attenuation is higher at CT X-ray energy than at PET energy (12). This therefore leads to an overestimation of attenuation, which results in artifactually increased FDG activity in CT attenuation-corrected PET images (12) (Figure 13). If an artifact is suspected, then confirmation is made by evaluating the non–attenuation-corrected images. This is to prevent erroneous misinterpretation of increased uptake as disease.