Pitfalls in Oncologic Diagnosis with FDG PET Imaging: Physiologic and Benign Variants

A rapidly emerging clinical application of positron emission tomography (PET) is the detection and staging of cancer with the glucose analogue tracer 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG). Proper interpretation of FDG PET images requires knowledge of the normal physiologic distribution of the tracer, frequently encountered physiologic variants, and benign pathologic causes of FDG uptake that can be confused with a malignant neoplasm. One hour after intravenous administration, high FDG activity is present in the brain, the myocardium, and—due to the excretory route—the urinary tract. Elsewhere, tracer activity is typically low, a fact that allows sensitive demonstration of tracer accumulation in many malignant neoplasms. Interpretive pitfalls commonly encountered on FDG PET images of the body obtained 1 hour after tracer administration can be mistaken for cancer. Such pitfalls include variable physiologic FDG uptake in the digestive tract, thyroid gland, skeletal muscle, myocardium, bone marrow, and genitourinary tract and benign pathologic FDG uptake in healing bone, lymph nodes, joints, sites of infection, and cases of regional response to infection and aseptic inflammatory response. In many instances, these physiologic variants and benign pathologic causes of FDG uptake can be specifically recognized and properly categorized; in other instances, such as the lymph node response to inflammation or infection, focal FDG uptake is nonspecific.


  • 1 Rigo P, Paulus P, Kaschten BJ, et al. Oncologic applications of positron emission tomography with fluorine-18 fluorodeoxyglucose. Eur J Nucl Med 1996; 23:1641-1674. Crossref, MedlineGoogle Scholar
  • 2 Hamberg LM, Hunter GJ, Alpert NM, Choi NC, Babich JW, Fischman AJ. The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification? J Nucl Med 1994; 35:1308-1312. MedlineGoogle Scholar
  • 3 Jones SC, Alavi A, Christman D, Montanez I, Wolf AP, Reivich M. The radiation dosimetry of 2-[F-18] fluoro-2-deoxy-d-glucose in man. J Nucl Med 1982; 23:613-617. MedlineGoogle Scholar
  • 4 Lindholm P, Minn H, Leskinen-Kallio S, Bergman J, Ruotsalainen U, Joensuu H. Influence of the blood glucose concentration on FDG uptake in cancer: a PET study. J Nucl Med 1993; 34:1-6. MedlineGoogle Scholar
  • 5 Minn H, Leskinen-Kallio S, Lindholm P, et al. [18F] fluorodeoxyglucose uptake in tumors: kinetic vs. steady-state methods with reference to plasma insulin. J Comput Assist Tomogr 1993; 17:115-123. Google Scholar
  • 6 Torizuka T, Fisher SJ, Wahl RL. Insulin-induced hypoglycemia decreases uptake of 2-[F-18]fluoro-2-deoxy-d-glucose into experimental mammary carcinoma. Radiology 1997; 203:169-172. LinkGoogle Scholar
  • 7 Dahlbom M, Hoffman EJ, Hoh CK, et al. Whole-body positron emission tomography: methods and performance characteristics. J Nucl Med 1992; 33:1191-1199. MedlineGoogle Scholar
  • 8 Zasadny KR, Kison PV, Quint LE, Wahl RL. Untreated lung cancer: quantification of systematic distortion of tumor size and shape on non–attenuation-corrected 2-[fluorine-18]fluoro-2-deoxy-d-glucose PET scans. Radiology 1996; 201:873-876. LinkGoogle Scholar
  • 9 Bailey DL. Transmission scanning in emission tomography. Eur J Nucl Med 1998; 25:774-787. Crossref, MedlineGoogle Scholar
  • 10 Bengel FM, Ziegler SI, Avril N, Weber W, Laubenbacher C, Schwaiger M. Whole-body positron emission tomography in clinical oncology: comparison between attenuation-corrected and uncorrected images. Eur J Nucl Med 1997; 24:1091-1098. Crossref, MedlineGoogle Scholar
  • 11 Imran MB, Kubota K, Yamada S, et al. Lesion-to-background ratio in non–attenuation-corrected whole-body FDG PET images. J Nucl Med 1998; 39:1219-1223. MedlineGoogle Scholar
  • 12 Vesselle HJ, Miraldi FD. FDG PET of the retroperitoneum: normal anatomy, variants, pathologic conditions, and strategies to avoid diagnostic pitfalls. RadioGraphics 1998; 18:805-823. LinkGoogle Scholar
  • 13 Bedigian MP, Benard F, Smith RJ, Karp JS, Alavi A. Whole-body positron emission tomography for oncology imaging using singles transmission scanning with segmentation and ordered subsets–expectation maximization (OS-EM) reconstruction. Eur J Nucl Med 1998; 25:659-661. Crossref, MedlineGoogle Scholar
  • 14 Hamberg LM, Hunter GJ, Alpert NM, Choi NC, Babich JW, Fischman AJ. The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification? J Nucl Med 1994; 35:1308-1312. MedlineGoogle Scholar
  • 15 Torizuka T, Zasadny KR, Recker B, Wahl RL. Untreated primary lung and breast cancers: correlation between F-18 FDG kinetic rate constants and findings of in vitro studies. Radiology 1998; 207:767-774. LinkGoogle Scholar
  • 16 Zasadny KR, Wahl RL. Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose: variations with body weight and a method for correction. Radiology 1993; 189:847-850. LinkGoogle Scholar
  • 17 Keyes JW, Jr. SUV: standard uptake or silly useless value? J Nucl Med 1995; 36:1836-1839. MedlineGoogle Scholar
  • 18 Stollfuss JC, Glatting G, Friess H, Kocher F, Beger HG, Reske SN. 2-(fluorine-18)-fluoro-2-deoxy-d-glucose PET in detection of pancreatic cancer: value of quantitative image interpretation. Radiology 1995; 195:339-344. LinkGoogle Scholar
  • 19 Lowe VJ, Fletcher JW, Gobar L. Prospective investigation of positron emission tomography in lung nodules. J Clin Oncol 1998; 16:1075-1084. Crossref, MedlineGoogle Scholar
  • 20 Brigid GA, Flanagan FL, Dehdashti F. Whole-body positron emission tomography: normal variations, pitfalls, and technical considerations. AJR 1997; 169:1675-1680. Crossref, MedlineGoogle Scholar
  • 21 Meyer MA. Diffusely increased colonic F-18 FDG uptake in acute enterocolitis. Clin Nucl Med 1995; 20:434-435. Crossref, MedlineGoogle Scholar
  • 22 Miraldi F, Vesselle H, Faulhaber PF, Adler LP, Leisure GP. Elimination of artifactual accumulation of FDG in PET imaging of colorectal cancer. Clin Nucl Med 1998; 23:3-7. Crossref, MedlineGoogle Scholar
  • 23 Conti PS, Durski JM, Singer PA, Austin T. Incidence of thyroid gland uptake of F-18 FDG in cancer patients (abstr). Radiology 1997; 205(P):220. Google Scholar
  • 24 Jabour BA, Choi Y, Hoh CK, et al. Extracranial head and neck: PET imaging with 2-[F-18]fluoro-2-deoxy-d-glucose and MR imaging correlation. Radiology 1993; 186:27-35. LinkGoogle Scholar
  • 25 Barrington SF, Maisey MN. Skeletal muscle uptake of fluorine-18-FDG: effect on oral diazepam. J Nucl Med 1996; 37:1127-1129. MedlineGoogle Scholar
  • 26 Kostakoglu L, Wong JCH, Barrington SF, Cronin BF, Dynes AM, Maisey MN. Speech-related visualization of laryngeal muscles with fluorine-18-FDG. J Nucl Med 1996; 37:1771-1773. MedlineGoogle Scholar
  • 27 Mossberg KA, Mommessin JI, Taegtmeyer H. Skeletal muscle glucose uptake during short-term contractile activity in vivo: effect of prior contractions. Metabolism 1993; 42:1609-1616. Crossref, MedlineGoogle Scholar
  • 28 Cook GJR, Fogelman I, Maisey MN. Normal physiological and benign pathological variants of 18-fluoro-2-deoxyglucose positron-emission tomography scanning: potential for error in interpretation. Semin Nucl Med 1996; 26:308-314. Crossref, MedlineGoogle Scholar
  • 29 Engel H, Steinert H, Buck A, Berthold T, Huch Boni RA, von Schulthess GK. Whole-body PET: physiological and artifactual fluorodeoxyglucose accumulations. J Nucl Med 1996; 37:441-446. MedlineGoogle Scholar
  • 30 Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and the energy balance of heat muscle. Annu Rev Physiol 1974; 36:413-459. Crossref, MedlineGoogle Scholar
  • 31 Sugawara Y, Fisher SJ, Zasadny KR, Kison PV, Baker LH, Wahl RL. Pre-clinical and clinical studies of bone marrow uptake of fluorine-18-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy. J Clin Oncol 1998; 16:173-180. Crossref, MedlineGoogle Scholar
  • 32 Kosuda S, Fisher S, Kison PV, Wahl RL, Grossman HB. Uptake of 2-deoxy-2-[18F]fluoro-d-glucose in the normal testis: retrospective PET study and animal experiment. Ann Nucl Med 1997; 11:195-199. Crossref, MedlineGoogle Scholar
  • 33 Meyer M, Gast T, Raja S, Hubner K. Increased F-18 FDG accumulation in an acute fracture. Clin Nucl Med 1994; 19:13-14. Crossref, MedlineGoogle Scholar
  • 34 Lewis PJ, Salama A. Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis. J Nucl Med 1994; 35:1647-1649. MedlineGoogle Scholar
  • 35 Strauss LG. Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients. Eur J Nucl Med 1996; 23:1409-1415. Crossref, MedlineGoogle Scholar
  • 36 Tahara T, Ichiya Y, Kuwabara U, et al. High [18F]-fluorodeoxyglucose uptake in abdominal abscesses: a PET study. J Comput Assist Tomogr 1989; 13:829-831. Crossref, MedlineGoogle Scholar
  • 37 Yasuda S, Shohtsu A, Ide M, Takagi S, Kijima H, Horiuchi M. Elevated F-18 FDG uptake in plasmacyte-rich chronic maxillary sinusitis. Clin Nucl Med 1998; 23:176-178. Crossref, MedlineGoogle Scholar
  • 38 Shreve PD. Focal flourine-18 fluorodeoxyglucose accumulation in inflammatory pancreatic disease. Eur J Nucl Med 1998; 25:259-264. Crossref, MedlineGoogle Scholar
  • 39 Friess H, Langhans J, Ebert M, et al. Diagnosis of pancreatic cancer by 2[18F]-fluoro-2-deoxy-d-glucose positron emission tomography. Gut 1995; 36:771-777. Crossref, MedlineGoogle Scholar

Article History

Accepted: Oct 13 1998
Received: Mar 04 1998
Revision received: May 01 1998
Revision received: Sept 29 1998
Published in print: Jan 1999