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Positron Emission Tomography/Computed Tomography (PET/CT) is a noninvasive diagnostic imaging procedure that has been increasingly utilized in many oncologic applications. Patients undergoing PET/CT are injected with a radiotracer, which accumulates in certain normal and abnormal structures. Currently, the glucose analogue [18F] Fluoro-2-deoxy-2-D-glucose or [18F-FDG] is the preferred radioactive tracer for PET/CT examinations to diagnose, stage, and restage cancer. After the process of phosphorylation of the glucose analogue, FDG-6-phosphate is tapped in body cells, thus allowing imaging of different organs and tissues. Unfortunately, not only do malignant tumors show a higher uptake of FDG on PET/CT scans but so do some non-neoplastic and normal physiologic conditions; this may obscure or mimic the appearance of malignant neoplasms, thus increasing the number of false positive or negative findings on FDG PET/CT images (Long & Smith, 2011).
One of the physiologic conditions that might lead to a false positive or negative result is the normal uptake of FDG within brown fat and working muscles. According to Long and Smith (2011), brown fat uptake has been clearly recognized in several studies as one of the potential causes of false positive findings. It was reported that approximately 3 or 4 out of 100 FDG PET/CT scans would show brown fat uptake; in the mediastinum region, this can be mistakenly diagnosed as nodular metastatic lesions detected around several structures—including the trachea, esophagus, and pericardium—resulting in false positive results. Brown fat uptake is more common in females and children than it is in males or adults. The effect of brown fat uptake increases in cold weather and in people with low BMI. Thus, it is recommended that during the uptake time, the patient body temperature be maintained with warm blankets and warm room temperature (Long & Smith, 2011).
In addition, Jadvar and Parker (2005) stated that another potential source of false findings commonly seen in FDG studies is the high uptake of FDG in working skeletal muscles. The increased activity in working muscles can limit lesion detection, thus increasing the incidence of false negative results. For example, a high uptake in the mastication muscles (Musculi masticatorii) from chewing or eating can hide lesions in the head or neck regions. Therefore, patients are advised not to eat and to relax after FDG injection. According to Long and Smith (2011) the high uptake of FDG in inflammatory and infected cells as a result of chemotherapy can be a potential cause of false positive PET/CT studies for cancer. It has been shown that an increased uptake in neutrophil granulocytes and activated macrophages may mimic the appearance of malignant tumors. Change et al. (2006) stated that non-neoplastic tissue is attributed to 40% of FDG uptake after therapy. Unfortunately, many cancer patients become vulnerable to infections after undergoing chemotherapy (Long & Smith, 2011). Jadvar and Parker (2005) stated that “active infections such as pneumonia, tuberculosis, histoplasmosis, toxoplasmosis, cryptococcoma, and coccidioidomycosis may demonstrate very high FDG uptake, therapy diminishing the specificity of PET in characterizing lesions” (p. 259).
Another potential cause of false positive finding is normal FDG uptake in the gastrointestinal tract. This type of pattern in GI uptake has been shown in several studies. It is believed that smooth muscle movement and swallowed secretions are the causes of FDG uptake in the GI tract. Jadvar and Parker (2005) have explained that normal uptake in the bowel increases the difficulty for detection of tumors in the abdomen and pelvic regions, contributing to false negative and positive results in FDG PET/CT. For example, the stomach may show a normal high uptake of FDG that might falsely diagnose as neoplasms. In addition, moderate non-homogeneous uptake is a typical appearance of FDG in the small intestine. However, underdistention or overlapping of bowel loops causes the appearance of high uptake that could either mimic or conceal lesions (Long & Smith, 2011). Cook, Wegner, and Forgelman (2004) stated that eliminating the effect of normal bowel uptake can be achieved by one of several methods, such as the use of glucagon, anticholinergics, or laxatives prior to the procedure, thus reducing the number of false positive and negative findings and improving diagnostic accuracy in the detection of lesions in the bowel. Additionally, non-hypermetabolic lesions and tumors with low-grade histologies are potential sources for false negative findings on PET/CT images. According to Jadvar and Parker (2005), several types of neoplasm are not hypermetabolic lesions and potentially would not be captured on [18F-FDG] scans. For example, bronchioloalveolar carcinoma shows low standardized uptake values (SUVs) compared to other lung cancers (Chang, 2006). Other examples of low metabolic tumors are renal cell carcinoma, hepatocellular carcinoma, and carcinoid lesions. Moreover, several low-grade neoplasms, such as lymphomas and gliomas, show up with low to mild activity that sometime result in misdiagnosis of these lesions. However, misinterpretation of PET/CT studies can be avoided by careful examination of the CT results (Long & Smith, 2011).
In conclusion, 18F-FDG PET/CT metabolic imaging is becoming a significantly important tool in the evaluation of oncologic conditions. Despite its accuracy in the detection of many malignancies, many factors and conditions—such as normal uptake in the GI tract, non-neoplastic diseases, infection, inflammation, and low-grade tumors—might lead to false positive or negative FDG PET/CT results.
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