Anatomic, functional imaging collaborate in cancer detection

February 4, 2005

Several oncologic imaging modalities have evolved significantly since CT was developed in 1973. Although CT provides a noninvasive method for evaluating cancer patients, first-generation scanners were limited in their speed of data acquisition and spatial resolution. Current multislice CT scanners can evaluate a patient completely, with exquisite anatomic detail, in as little as 15 to 30 seconds.

Several oncologic imaging modalities have evolved significantly since CT was developed in 1973. Although CT provides a noninvasive method for evaluating cancer patients, first-generation scanners were limited in their speed of data acquisition and spatial resolution. Current multislice CT scanners can evaluate a patient completely, with exquisite anatomic detail, in as little as 15 to 30 seconds.

When MR imaging became available in 1983, it made further characterization of suspected malignant lesions possible, often adding complementary information to that found on CT.

Ultrasound, too, offers additional information for evaluation and characterization of several potential malignant lesions. Ultrasound, CT, and MR remain major imaging modalities in clinical oncology, but they generally offer little information regarding the metabolic derangements of tumors. With the use of 2-fluoro-deoxyglucose (FDG) PET imaging, a radioactive glucose analog is injected into patients, and a sensitive coincidence detector system maps the radioactivity.

It has been known since Warburg's observations in the 1930s that many tumors are hypermetabolic compared with surrounding normal tissue, and, therefore, visualization of many tumor types became possible with FDG-PET.1 However, PET imaging provides only limited anatomic detail, and some tumors do not readily take up FDG, making them relatively or absolutely undetectable by FDG-PET (Table 1).

The underlying aberration of cancer is abnormal cellular division and proliferation, which indirectly causes increased metabolic rates for most malignancies. The anatomic findings identified on CT and/or MR in general tend to be later manifestations relative to the functional changes in tumors. FDG-PET can potentially demonstrate metabolic abnormalities earlier in the disease process and enable further characterization of many malignant lesions.

It makes sense, then, that combining an anatomic scanner (CT or MR) with a functional scanner (PET) might be the optimal imaging modality for evaluating oncologic patients. In 1998, the first prototype combined PET/CT scanner was developed at the University of Pittsburgh, and clinical PET/CT scanners became commercially available in 2001.

Although FDG-PET imaging has been in existence since 1976, it wasn't until 1998, when the Centers for Medicare and Medicaid Services announced reimbursement for FDG-PET for several indications (Table 2), that the modality began to be used more frequently. Several valuable clinical applications for FDG- PET can extend to many of the covered indications (Table 3).

- Screening. A few large studies have examined the utility of FDG-PET as a potential oncologic screening tool in asymptomatic patients, with a 2% to 3% detection rate of unsuspected malignancies in the general population.2 The current cost of the procedure outweighs the potential benefits, however, and prohibits its widespread use as a cancer screening modality. False-positive studies are an additional undesirable consequence of screening that also outweighs the potential benefits, due to excessive costs of further evaluation and morbidity from biopsies and other unnecessary invasive diagnostic procedures.

- Carcinoma of unknown primary. Medicare and most third-party payers do not reimburse for FDG-PET imaging of carcinoma of unknown primary (CUP), although up to 5% of all cancer patients receive this diagnosis. FDG-PET has been used to detect and localize primary malignancies, with a detection rate ranging from 43% to 48%.3,4 PET has been shown to influence management in up to 69% of patients for whom it is used to evaluate CUP. Although FDG-PET can be helpful in diagnostically challenging CUP patients, one study reported two-false negative PET exams, reinforcing the fact that absence of an abnormality on FDG-PET does not exclude the presence of disease.

- Differentiating benign from malignant lesions. The most common indication for a PET scan is to evaluate a radiographically indeterminate solitary pulmonary nodule. FDG-PET has been shown in several studies to be more accurate in differentiating benign from malignant nodules larger than 1 cm.5-9 The sensitivity and specificity for all lung nodules is approximately 97% and 78%, respectively, as reported in a meta-analysis evaluating 40 studies and 1474 lung nodules examined with FDG-PET.9

Although FDG-PET can be used to evaluate hepatic, pancreatic, splenic, and other masses or nodules in patients without a pathologic diagnosis of malignancy, a negative PET study in this patient population is often denied by third-party payers. They argue that the test was performed for the evaluation of an unknown primary tumor, currently a nonreimbursable CMS indication.

- Staging following initial diagnosis. FDG-PET has been shown to have a higher sensitivity and at times a higher specificity than CT and/or MR imaging for evaluation of many FDG-avid malignancies, including lung, colorectal, esophageal, and head and neck cancer, as well as lymphoma and melanoma.10-22 The evidence is compelling enough in the staging of these malignancies that the addition of PET imaging has been recommended as the standard of care rather than optional evaluation (Figure 1).23

- Restaging. Several studies have also shown the utility of FDG-PET for many restaging applications in patients with various malignancies. These applications include differentiation of scar from recurrent tumor, evaluation of patients with elevated tumor markers, and surveillance of asymptomatic patients following therapy.24-30 Further, therapy monitoring (Figures 2 and 3) and tracking overall response to therapy are important restaging applications in which evaluation of early metabolic changes following chemotherapy has been shown to be more useful than using traditional anatomic imaging modalities.31-40

LIMITATIONS

The main limitations of PET imaging are the lack of anatomic detail and the inability to evaluate for the presence of microscopic disease and smaller non-FDG-avid tumors. The absolute level of spatial resolution is approximately 5 to 6 mm using current technology.

The remaining limitations of PET imaging are primarily those of FDG, the only FDA-approved oncologic radiotracer. Although many tumor types take up FDG, due to their inherent metabolic upregulation, several malignancies have much less or no FDG uptake. Among these are hepatocellular carcinoma, neuroendocrine tumors, and even some lung cancers, such as bronchoalveolar cell carcinoma among others. (Figure 4).

Several other radiotracers in development focus on examining other cellular processes. One promising radiotracer is 3' deoxy-3'-[F-18] fluorothymidine (FLT), a thymidine analog that reflects cellular proliferation rather than metabolism, although data supporting its routine use are limited.41-46 FLT is also taken up intensely by the liver and bone marrow physiologically, making it an unlikely candidate for single radiotracer evaluation.

CT AND MR

CT is the imaging modality most commonly used to evaluate patients with cancer. It is ubiquitous in the medical imaging community and offers superb visualization of internal structures. Current 16 to 64-slice CT scanners provide the ability to obtain true isotropic data sets that permit manipulation of data and visualization of anatomy in axial, coronal, or sagittal planes without loss of anatomic resolution. Volumetric analysis of pulmonary nodules and continued development of CT colonography and other potential screening applications, which have helped reduce the number of more invasive procedures, will undoubtedly play an increasing role.

Using different protocols with intravenous and oral contrast and obtaining data during different phases of contrast enhancement, CT can accurately evaluate many tumors.

MRI is used much less frequently than CT and PET for oncologic applications, with the exception of primary and metastatic brain tumors, for which it is the diagnostic imaging modality of choice. However, MR offers complementary information in many oncologic applications, including liver, renal, and pancreatic mass evaluation. In the case of indeterminate adrenal nodules and masses, MR imaging can help differentiate adrenal adenoma from other, more potentially malignant diagnoses.

LIMITATIONS

The primary limitation of CT is its inability to evaluate the metabolic derangements of tumors. The anatomic detail is much better than can be obtained with PET, but post-treatment changes due to surgery and/or radiation therapy may appear identical to recurrent malignancy on CT. On PET imaging, however, scarring should have no FDG uptake and can easily be differentiated from FDG-avid tumor. In addition, most small malignant lymph nodes, prior to becoming enlarged, appear identical to normal lymph nodes on CT and often on MR. The criteria for differentiating a benign from malignant lymph node, including necrosis, enhancement, and mass effect, are all late manifestations of malignant involvement.

MR imaging has logistical limitations, including the relative inability to scan claustrophobic patients and those with contraindications such as implanted pacemakers and other metallic devices. Otherwise, MR's limitations are similar to those of CT, including the relative inability to determine involvement of normal-sized malignant lymph nodes and to distinguish post-treatment changes from recurrent tumor. Although more functional MR studies and protocols are being developed and performed, MR generally provides limited metabolic/functional information in comparison with PET imaging.

COMBINED PET/CT

Given the increasing utilization and acceptance of PET imaging in oncology, but also its severe limitations without anatomic correlation, combining PET and CT into a single examination is obviously beneficial. But there are many unexpected synergistic benefits, as well. Performing combined PET/CT rather than PET and CT separately not only consolidates the patient's imaging procedures but also expedites scan times and patient throughput because it avoids a separate PET transmission scan.

The most notable clinical benefit of combined PET/CT is improved lesion localization. Several authors report significant changes and improvement in lesion localization when comparing the PET portion of a PET/CT with fused PET/CT images.47-51

One of the most frustrating aspects of FDG-PET imaging alone is the lack of anatomic landmarks and the inherent uncertainty in localizing areas of FDG accumulation. It is often difficult or impossible to differentiate specific areas of FDG uptake as physiologic or pathologic, given the variable physiologic uptake of FDG in bowel, skeletal muscle, glands, and the genitourinary system.52 By fusing accurately coregistered PET and CT data sets, PET/CT significantly reduces the magnitude of mislocalization of FDG uptake and improves the confidence level of the interpreting physician in precisely localizing lesions.53 Published case reports and series also document how visualizing the fused images helped to resolve potential misinterpretation of benign processes as malignant.54-63

Several reports in the last three years have demonstrated the improved performance and the incremental value of PET/CT over PET, CT, or PET and CT performed separately for staging patients with Hodgkin's and non-Hodgkin's lymphoma and lung and colorectal cancer.64-70

PET/CT has been reported to affect patient management, particularly in radiation therapy evaluation and planning.47,68,71-74 PET/CT scanners were designed to accommodate flat radiation therapy planning pallets. As long as patient movement is minimized between the two scans, accurate coregistration of the two data sets is possible using fusion software, which most radiation therapy planning systems offer. With accurate coregistration, it is possible to view any blended combination of data.

Therapy planning for patients undergoing radiation has traditionally been based solely on anatomic information from a CT scan performed with an approved radiation therapy immobilization pallets. With PET/CT performed with a flat pallets, both the CT and PET data sets can be exported from the acquisition workstation and imported into radiation planning software systems. The patient's radiation therapy plan can then be designed with consideration of not only anatomic information but also metabolic data. This is particularly important for lesions that do not demonstrate a definite anatomic abnormality. When a lesion or the extent of a lesion cannot be adequately identified on the CT portion of the exam, radiation oncologists can integrate the metabolic information from PET for their contouring.

One of the most beneficial applications of combined PET/CT is in restaging patients who have undergone extensive surgery or radiation therapy, both of which tend to distort normal anatomy and cause inflammatory tissue changes. The importance and utility of PET/CT in the restaging of several malignancies, including head and neck, colorectal, thyroid, ovarian cancer, and lymphoma, have also has been reported.64,67,75-77

References

1. Warburg O. The metabolism of tumors. Science 1931:129-169.

2. Yasuda S, Ide M, Fujii H, et al. Application of positron emission tomography imaging to cancer screening. Br J Cancer 2000;83(12):1607-1611.

3. Mantaka P, Baum RP, Hertel A, et al. PET with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with cancer of unknown primary (CUP): influence on patients' diagnostic and therapeutic management. Cancer Biother Radiopharm 2003;18(1):47-58.

4. Rades D, Kuhnel G, Wildfang I, et al. Localised disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management. Ann Oncol 2001;12(11):1605-1609.

5. Herder GJ, Golding RP, Hoekstra OS, et al. The performance of (18)F-fluorodeoxyglucose positron emission tomography in small solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 2004;31(9):1231-1236.

6. Belohlavek O, Kosatova K, Melinova L, et al. Metabolic characterisation of solitary pulmonary nodules by positron emission tomography with FDG-preliminary report. Nucl Med Rev Cent East Eur 2001;4(2):97-100.

7. Bury T, Dowlati A, Paulus P, et al. Evaluation of the solitary pulmonary nodule by positron emission tomography imaging. Eur Respir J 1996;9(3):410-414.

8. Gambhir SS, Shepherd JE, Shah BD, et al. Analytical decision model for the cost-effective management of solitary pulmonary nodules. J Clin Oncol 1998;16(6):2113-2125.

9. Gould MK, Maclean CC, Kuschner WG, et al. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285(7):914-924.

10. Wahl RL, Quint LE, Greenough RL, et al. Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation. Radiology 1994;191(2):371-377.

11. Laubenbacher C, Saumweber D, Wagner-Manslau C, et al. Comparison of fluorine-18-fluorodeoxyglucose PET, MRI and endoscopy for staging head and neck squamous-cell carcinomas. J Nucl Med 1995;36(10):1747-1757.

12. Steinert HC, Hauser M, Allemann F, et al. Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling. Radiology 1997;202(2):441-446.

13. Adams S, Baum RP, Stuckensen T, et al. Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med 1998;25(9):1255-1260.

14. Schrevens L, Lorent N, Dooms C, Vansteenkiste J. The role of PET scan in diagnosis, staging, and management of non-small cell lung cancer. Oncologist 2004;9(6):633-643.

15. Halter G, Buck AK, Schirrmeister H, et al. Lymph node staging in lung cancer using [18F]FDG-PET. Thorac Cardiovasc Surg 2004;52(2):96-101.

16. Kantorova I, Lipska L, Belohlavek O, et al. Routine (18)F-FDG PET preoperative staging of colorectal cancer: comparison with conventional staging and its impact on treatment decision making. J Nucl Med 2003;44(11):1784-88.

17. Wahl RL. Current status of PET in breast cancer imaging, staging, and therapy. Semin Roentgenol 2001;36(3):250-260.

18. Richter JA, Garcia-Velloso MJ, Perez-Equiza C, et al. PET-FDG versus CT in the staging and detection of relapse in patients with Hodgkin's disease or non-Hodgkin lymphoma. Two years experience. Clin Positron Imaging 1998;1(4):248.

19. Vansteenkiste JF, Stroobants SG, De Leyn PR, et al. Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients. J Clin Oncol 1998;16(6):2142-2149.

20. Coleman RE. PET in lung cancer staging. Q J Nucl Med 2001;45(3):231-234.

21. Jerusalem G, Beguin Y, Najjar F, et al. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL). Ann Oncol 2001;12(6):825-830.

22. Brink I, Schumacher T, Mix M, et al. Impact of [(18)F]FDG-PET on the primary staging of small-cell lung cancer. Eur J Nucl Med Mol Imaging 2004;31(12):1614-1620.

23. Bourguet P, Blanc-Vincent MP, Boneu A, et al. Summary of the standards, options and recommendations for the use of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET scanning) in oncology (2002). Br J Cancer 2003;89 suppl 1:S84-S91.

24. Wiering B, Ruers TJ, Oyen WJ. Role of FDG-PET in the diagnosis and treatment of colorectal liver metastases. Expert Rev Anticancer Ther 2004;4(4):607-613.

25. Yen TC, See LC, Chang TC, et al. Defining the priority of using 18F-FDG PET for recurrent cervical cancer. J Nucl Med 2004;45(10):1632-1639.

26. Goerres GW, Mosna-Firlejczyk K, Steurer J, et al. Assessment of clinical utility of 18F-FDG PET in patients with head and neck cancer: a probability analysis. Eur J Nucl Med Mol Imaging 2003;30(4):562-571.

27. Becherer A, Jaeger U, Szabo M, Kletter K. Prognostic value of FDG-PET in malignant lymphoma. Q J Nucl Med 2003;47(1):14-21.

28. Ryu JS, Choi NC, Fischman AJ, et al. FDG-PET in staging and restaging non-small cell lung cancer after neoadjuvant chemoradiotherapy: correlation with histopathology. Lung Cancer 2002;35(2):179-187.

29. Goerres GW, Stoeckli SJ, von Schulthess GK, Steinert HC. FDG PET for mucosal malignant melanoma of the head and neck. Laryngoscope 2002;112(2):381-385.

30. Spaepen K, Stroobants S, Dupont P, et al. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol 2001;19(2):414-419.

31. Jerusalem G, Beguin Y, Fassotte MF, et al. Persistent tumor 18F-FDG uptake after a few cycles of polychemotherapy is predictive of treatment failure in non-Hodgkin's lymphoma. Haematologica 2000;85(6):613-618.

32. Weber WA, Schwaiger M, Avril N. Quantitative assessment of tumor metabolism using FDG-PET imaging. Nucl Med Biol 2000;27(7):683-687.

33. Mikhaeel NG, Timothy AR, O'Doherty MJ, et al. 18-FDG-PET as a prognostic indicator in the treatment of aggressive non-Hodgkin's lymphoma-comparison with CT. Leuk Lymphoma 2000;39(5-6):543-553.

34. Spaepen K, Mortelmans L. Evaluation of treatment response in patients with lymphoma using [18F]FDG-PET: differences between non-Hodgkin's lymphoma and Hodgkin's disease. Q J Nucl Med 2001;45(3):269-273.

35. Kostakoglu L, Goldsmith SJ. 18F-FDG PET evaluation of the response to therapy for lymphoma and for breast, lung, and colorectal carcinoma. J Nucl Med 2003;44(2):224-239.

36. Spaepen K, Stroobants S, Dupont P, et al. [(18)F]FDG PET monitoring of tumour response to chemotherapy: does [(18)F]FDG uptake correlate with the viable tumour cell fraction? Eur J Nucl Med Mol Imaging 2003;30(5):682-688.

37. Spaepen K, Stroobants S, Verhoef G, Mortelmans L. Positron emission tomography with [(18)F]FDG for therapy response monitoring in lymphoma patients. Eur J Nucl Med Mol Imaging 2003;30 suppl 1:S97-S105.

38. Torizuka T, Nakamura F, Kanno T, et al. Early therapy monitoring with FDG-PET in aggressive non-Hodgkin's lymphoma and Hodgkin's lymphoma. Eur J Nucl Med Mol Imaging 2004;31(1):22-28.

39. Grigsby PW, Siegel BA, Dehdashti F, Mutch DG. Posttherapy surveillance monitoring of cervical cancer by FDG-PET. Int J Radiat Oncol Biol Phys 2003;55(4):907-913.

40. Dimitrakopoulou-Strauss A, Strauss LG, Rudi J. PET-FDG as predictor of therapy response in patients with colorectal carcinoma. Q J Nucl Med 2003;47(1):8-13.

41. Shields AF, Grierson JR, Dohmen BM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 1998;4(11):1334-1336.

42. Rasey JS, Grierson JR, Wiens LW, et al. Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med 2002;43(9):1210-1217.

43. Buck AK, Halter G, Schirrmeister H, et al. Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med 2003;44(9):1426-1431.

44. Dittmann H, Dohmen BM, Paulsen F, et al. [18F]FLT PET for diagnosis and staging of thoracic tumours. Eur J Nucl Med Mol Imaging 2003;30(10):1407-1412.

45. Shields AF. PET imaging with 18F-FLT and thymidine analogs: promise and pitfalls. J Nucl Med 2003;44(9):1432-1434.

46. Cobben DC, van der Laan BF, Maas B, et al. 18F-FLT PET for visualization of laryngeal cancer: comparison with 18F-FDG PET. J Nucl Med 2004;45(2):226-231.

47. Bar-Shalom R, Yefremov N, Guralnik L, et al. Clinical performance of PET/CT in evaluation of cancer: additional value for diagnostic imaging and patient management. J Nucl Med 2003;44(8):1200-1209.

48. Hany TF, Steinert HC, Goerres GW, et al. PET diagnostic accuracy: improvement with in-line PET-CT system: initial results. Radiology 2002;225(2):575-581.

49. Osman MM, Cohade C, Nakamoto Y, et al. Clinically significant inaccurate localization of lesions with PET/CT: frequency in 300 patients. J Nucl Med 2003;44(2):240-243.

50. Israel O, Mor M, Gaitini D, et al. Combined functional and structural evaluation of cancer patients with a hybrid camera-based PET/CT system using (18)F-FDG. J Nucl Med 2002;43(9):1129-1136.

51. Pelosi E, Messa C, Sironi S, et al. Value of integrated PET/CT for lesion localisation in cancer patients: a comparative study. Eur J Nucl Med Mol Imaging 2004;31(7):932-939.

52. Blodgett T, Fukui M, et al. Combined PET/CT in the head and neck part I: physiologic, altered physiologic and artifactual FDG uptake. Radiographics 2005: In press.

53. Branstetter BF, Blodgett TB, et al. Depiction of head and neck malignancy: is PET/CT more accurate than PET or CT alone? Radiology 2005: In press.

54. Yeretsian RA, Blodgett TM, Branstetter BF, et al. Teflon-induced granuloma: a false-positive finding with PET resolved with combined PET and CT. AJNR 2003;24(6):1164-1166.

55. Bar-Shalom R, Gaitini D, Keidar Z, Israel O. Non-malignant FDG uptake in infradiaphragmatic adipose tissue: a new site of physiological tracer biodistribution characterised by PET/CT. Eur J Nucl Med Mol Imaging 2004;31(8):1105-113.

56. Chander S, Meltzer CC, McCook BM. Physiologic uterine uptake of FDG during menstruation demonstrated with serial combined positron emission tomography and computed tomography. Clin Nucl Med 2002;27(1):22-24.

57. Kamel EM, Goerres GW, Burger C, et al. Recurrent laryngeal nerve palsy in patients with lung cancer: detection with PET-CT image fusion-report of six cases. Radiology 2002;224(1):153-156.

58. Keidar Z, Engel A, Nitecki S, et al. PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose for the evaluation of suspected infected vascular graft. Mol Imaging Biol 2003;5(1):23-25.

59. Tatsumi M, Cohade C, Nakamoto Y, Wahl RL. Fluorodeoxyglucose uptake in the aortic wall at PET/CT: possible finding for active atherosclerosis. Radiology 2003;229(3):831-837.

60. Heller MT, Meltzer CC, Fukui MB, et al. Superphysiologic FDG uptake in the non-paralyzed vocal cord. Resolution of a false-positive PET result with combined PET-CT imaging. Clin Positron Imaging 2000;3(5):207-211.

61. Goerres GW, Von Schulthess GK, Hany TF. Positron emission tomography and PET CT of the head and neck: FDG uptake in normal anatomy, in benign lesions, and in changes resulting from treatment. AJR 2002;179(5):1337-1343.

62. Cohade C, Osman M, Pannu HK, Wahl RL. Uptake in supraclavicular area fat ("USA-Fat"): description on 18F-FDG PET/CT. J Nucl Med 2003;44(2):170-176.

63. Weiss N, Solomon SB. Talc pleurodesis mimics pleural metastases: differentiation with positron emission tomography/computed tomography. Clin Nucl Med 2003;28(10):811-814.

64. Schaefer NG, Hany TF, Taverna C, et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging-do we need contrast-enhanced CT? Radiology 2004;232(3):823-829.

65. Ollenberger GP. Staging of lung cancer with integrated PET-CT. N Engl J Med 2004;350(1):86-87; author reply 86-87.

66. Lardinois D, Weder W, Hany TF, et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. NEJM 2003;348(25):2500-2507.

67. Cohade C, Osman M, Leal J, Wahl RL. Direct comparison of (18)F-FDG PET and PET/CT in patients with colorectal carcinoma. J Nucl Med 2003;44(11):1797-1803.

68. Antoch G, Stattaus J, Nemat AT, et al. Non-small cell lung cancer: dual-modality PET/CT in preoperative staging. Radiology 2003;229(2):526-533.

69. Martinelli M, Townsend D, Meltzer C, Villemagne VV. Survey of results of whole body imaging using the PET/CT at the University of Pittsburgh Medical Center PET facility. Clin Positron Imaging 2000;3(4):161.

70. Kluetz P, Villemagne VV, Meltzer C, et al. Prospective feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET and CT imaging. J Nucl Med 2004;45(4):543-552.

71. Bradley JD, Perez CA, Dehdashti F, Siegel BA. Implementing biologic target volumes in radiation treatment planning for non-small cell lung cancer. J Nucl Med 2004;45 suppl 1:96S-101S.

72. Bradley J, Thorstad WL, Mutic S, et al. Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004;59(1):78-86.

73. Ciernik IF, Dizendorf E, Baumert BG, et al. Radiation treatment planning with an integrated positron emission and computer tomography (PET/CT): a feasibility study. Int J Radiat Oncol Biol Phys 2003;57(3):853-863.

74. Bristow RE, del Carmen MG, Pannu HK, et al. Clinically occult recurrent ovarian cancer: patient selection for secondary cytoreductive surgery using combined PET/CT. Gynecol Oncol 2003;90(3):519-528.

75. Sironi S, Messa, C, et al. Integrated FDG PET/CT in patients with persistent ovarian cancer: correlation with histologic findings. Radiology 2004;233(2):433.

76. Pannu HK, Bristow RE, Cohade C, et al. PET-CT in recurrent ovarian cancer: initial observations. Radiographics 2004;24(1):209-223.

77. Pannu HK, Cohade C, Bristow RE, et al. PET-CT detection of abdominal recurrence of ovarian cancer: radiologic-surgical correlation. Abdom Imaging 2004;29(3):398-403.

Dr. Blodgett is a third-year diagnostic radiology resident, and Dr. Meltzer and Dr. Federle are professors of radiology, all at the University of Pittsburgh Medical Center.

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TABLE 1. VARIABLE AND NON-FDG-AVID TUMORS*

Bronchoalveolar cell carcinoma

Neuroendocrine tumors

Thyroid carcinoma

Hepatocellular carcinoma

Well-differentiated adenocarcinoma

Soft-tissue sarcoma

Prostate carcinoma

Cholangiocarcinoma

Pancreatic carcinoma

Esophageal carcinoma (well-differentiated adenocarcinomas)

*Partial list

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TABLE 2. CMS-COVERED INDICATIONS FOR FDG-PET

Solitary pulmonary nodules

Non-small cell lung carcinoma

Colorectal cancer

Lymphoma

Melanoma

Esophageal cancer

Head and neck cancers (excluding central nervous system cancers)

Thyroid cancer (excluding metastatic thyroid cancer)

Breast cancer

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TABLE 3. GENERAL CLINICAL APPLICATIONS

Differentiating benign vs. malignant lesions

Establishing grade of tumors

Biopsy localization information

Treatment planning

Establishing local extent of tumor

Detecting locoregional spread

Identifying distant metastases

Therapy monitoring

Detecting suspected recurrence

Restaging following relapse

Identifying primary disease