Fluorodeoxyglucose F 18 positron emission tomography scanning in thoracic disease.

Positron emission tomography (PET) is based on the observation that tumor cells exhibit high glucose utilization. (1) Though not unique to malignant cells, this feature prompted the development of a radiolabeled tagged glucose tracer that can assess tissue metabolism. Fluorodeoxyglucose F 18 (FDG) is the tracer most widely used in clinical practice. Positrons emitted from the tracer release two high-energy photons when they collide with electrons. Detectors record the dual photon emission, and computer software accurately maps their origin. Data can be displayed in individual planes or as a three-dimensional image. Scans are interpreted visually or quantitatively, using what is known as the standardized uptake value (SUV). A value greater than 2.5 is usually considered to indicate malignancy.

In the thorax, FDG PET is used to (a) evaluate solitary pulmonary nodules and other suspicious opacities, (b) stage lung cancer, (c) assess response to treatment of malignancy, (d) detect recurrence of malignancy, (e) evaluate soft tissue neoplasms, and (f) identify malignant pleural disease.

In the United States, a solitary pulmonary nodule (SPN) is identified in more than 150,000 patients annually. (2) Distinguishing benign from malignant lesions is difficult. (3) Computed tomography (CT) scanning is often inaccurate. Biopsy may not be definitive and has associated morbidity. Even when thoracoscopic lung biopsy is used to evaluate indeterminate SPNs, more than 50% of lesions are benign.

The ability of FDG PET to noninvasively distinguish benign from malignant lesions makes it an ideal tool for evaluating SPNs. More than 14 studies demonstrate that FDG PET has an overall average sensitivity of 95% (range, 86% to 100%), specificity of 88% (range, 58% to 100%), and accuracy of 90% (range, 81% to 100%), and FDG PET has also been shown to be more accurate than CT. (4) PET can significantly influence the treatment strategy; patients with positive scans may proceed to surgery, whereas patients with negative scans may be followed, usually by CT, to evaluate for growth over time. This may result in significant cost savings. (5)

Lung lesions with active inflammation such as pneumonia, lung abscess, or granulomas, can result in a false-positive scan. (6) In contrast, carcinoid tumors, bronchoalveolar cell carcinoma, and malignant lesions smaller than 1 cm may result in false-negative scans. PET is warranted as part of the initial evaluation of SPNs in the following situations: (1) lesions greater than 1 cm but less than 3 cm in diameter that are noncalcified (lesions >3 cm are frequently malignant); (2) patients who are high surgical risks, as surgical intervention would only be warranted if the PET scan was positive; and (3) in patients with a high probability of malignancy, based on clinical data, for whom proceeding directly to surgery is the most expeditious approach. PET should not be performed if the results will not affect treatment or if the patient is not considering surgery.

PET has proven valuable for staging non-small cell lung cancer. (7,8) In a meta-analysis of PET and CT studies used for staging purposes, the mean sensitivity and specificity for PET was 79% and 91%, respectively, in contrast to 60% and 77%, respectively, for CT. (9) A recent prospective trial of non-small cell lung cancer demonstrated that PET was superior to standard imaging approaches and biopsies for diagnosing both mediastinal and distant metastases. Preoperative staging was altered in 60% of cases. Estimates suggest that adding PET scanning to the preoperative workup of patients with negative mediastinal CT scans would prevent one unwarranted thoracotomy for every 10 PET scans performed. (10)

PET has been applied to the evaluation of suspected malignant pleural disease and soft tissue neoplasms. Bury et al (11) reported that PET had a sensitivity and specificity of 100% and 78%, respectively, in distinguishing benign from malignant pleural disease. PET can also differentiate malignant from benign effusions in patients with known lung cancer. (12,13)

In suspected cases of malignant mesothelioma, PET has proven useful. CT findings are frequently nonspecific, and thoracentesis and CT-guided biopsies can be insensitive. (14) Thoracoscopy has a higher yield, but nonlethal complications occur in approximately 10% of cases. (15) In contrast, malignant mesothelioma demonstrates significantly higher uptake values (SUV), compared with benign lesions, on PET. One study reported a sensitivity and specificity of 91% and 100%, respectively. (16)

In cases of benign fibrous mesothelioma or intrapulmonary localized fibrous tumor, PET data are limited. (17) In one report of three cases, all had negative PET scans (SUV <2.5). (18) However, the role of PET in this condition is still being evaluated.

In conclusion, FDG PET has become a valuable and cost-effective tool for distinguishing between benign and malignant thoracic disease and for improving staging of malignant thoracic neoplasms.

You cannot teach people anything. You can only help them discover it
within themselves.
--Galileo

Accepted October 23, 2003.

Please see "Diagnosis of Benign Solitary Fibrous Tumors by Positron Emission Tomography" on page 1264 of this issue.

References

1. Warburg O. The Metabolism of Tumors. London, Constable, 1931, 129-169.

2. Leef JL III, Klein JS. The solitary pulmonary nodule. Radiol Clin North Am 2002;40:123-143.

3. Tan BB, Flaherty KR, Kazerooni EA, et al. The solitary pulmonary nodule. Chest 2003;123(1 Suppl):89S-96S.

4. 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;285:914-924.

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

6. Goo JM, Im JG, Do KH, et al. Pulmonary tuberculoma evaluated by means of FDG PET: findings in 10 cases. Radiology 2000;216:117-121.

7. Chin R. Jr, Ward R, Keyes JW, et al.: Mediastinal staging of non-small-cell lung cancer with positron emission tomography. Am J Respir Crit Care Med. 1995;152:2090-2096.

8. Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000;27:254-261.

9. Dwamena BA, Sonnad SS, Angobaldo JO, et al. Metastases from non-small cell lung cancer: mediastinal staging in the 1990s: meta-analytic comparison of PET and CT. Radiology 1999;213:530-536.

10. Laking G, Price P. 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) and the staging of early lung cancer. Thorax 2001; 56(Suppl 2):ii-38-ii-44.

11. Bury T, Paulus P, Dowlati A, et al. Evaluation of pleural diseases with FDG-PET imaging: preliminary report. Thorax 1997;52:187-189.

12. Erasmus JJ, McAdams HP, Rossi SE, et al. FDG PET of pleural effusions in patients with non-small cell lung cancer. AJR Am J Roentgenol 2000;175:245-249.

13. Gupta NC, Rogers JS, Graeber GM, et al. Clinical role of F-18 fluorodeoxyglucose positron emission tomography imaging in patients with lung cancer and suspected malignant pleural effusion. Chest 2002;122:1918-1924.

14. Metintas M, Ozdemir N, Isiksoy S, et al. CT-guided pleural needle biopsy in the diagnosis of malignant mesothelioma. J Comput Assist Tomogr 1995;19:370-374.

15. Kaiser LR, Bavaria JE. Complications of thoracoscopy. Ann Thorac Surg 1993;56:796-798.

16. Benard F, Sterman D, Smith RJ, et al. Prognostic value of FDG PET imaging in malignant pleural mesothelioma. J Nucl Med 1999;40:1241-1245.

17. Rosado-De-Christenson ML, Abbott GF, McAdams HP, et al. From the Archives of the AFIP: localized fibrous tumors of the pleura. Radiographics 2003;23:759-783.

18. Cortes J, Rodriguez J, Garcia-Velloso MJ, et al. [(18)F]-FDG PET and localized fibrous mesothelioma [review]. Lung 2003;181:49-54.

Ruairi J. Fahy, MD, and Mark King, MD

From the Division of Pulmonary and Critical Care Medicine, Davis Heart and Lung Research Institute, and the Department of Radiology, The Ohio State University Medical Center, Columbus, OH.

Reprint requests to Dr. Ruairi J. Fahy, Division of Pulmonary and Critical Care Medicine, 201 Davis HLRI, The Ohio State University, 473 West 12th Avenue, Columbus, OH 43210-1252. Email: [e-mail]