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(Radiographics. 2000;20:1182-1185.)
© RSNA, 2000

PLENARY SESSION

1999 Plenary Session: Friday Imaging Symposium 1

Evaluation of Focal Pulmonary Abnormalities with FDG PET

Edward F. Patz, Jr, MD

1 From the Department of Radiology, Duke University Medical Center, Erwin Rd, Durham, NC 27710. From the Plenary Session, Friday Imaging Symposium: Algorithmic Controversies, at the 1999 RSNA scientific assembly. Received February 16, 2000; revision requested February 23 and received March 7; accepted March 8. Address correspondence to the author (e-mail: patz0002@mc.duke.edu).

Index Terms: Lung, diseases, 60.281, 60.31, 60.321 • Lung, nodule, 60.281, 60.31, 60.321 • Lung, PET, 60.12163 • Lung neoplasms, diagnosis, 60.12163 • Lung neoplasms, PET, 60.12163

Learning Objective

Describe FDG PET techniques and discuss the current applications of this modality in the evaluation of focal pulmonary abnormalities.

Introduction

Focal pulmonary abnormalities, which include the solitary pulmonary nodule, present a common, ongoing radiologic challenge. Some entities have characteristic imaging findings, whereas others remain indeterminate after conventional evaluation. More recently, positron emission tomography (PET) with 2-deoxy-2[fluorine-18]fluoro-D-glucose (FDG), a d-glucose analog labeled with positron-emitting F-18, has been used to evaluate focal pulmonary abnormalities and, in particular, to help differentiate benign from malignant lesions. In this article, the current applications of FDG PET in the evaluation of focal pulmonary abnormalities are discussed and illustrated.

Fundamentals of PET

The rationale for tumor imaging with FDG is based on a fundamental property of tumors, namely, increased glucose metabolism. This process begins when tumor cells take up and shuttle FDG into glycolysis. However, after the first phosphorylation step, FDG-6-phosphate becomes trapped and cannot proceed along the normal pathway. Increased amounts of FDG begin to accumulate within the malignant cells, and this abnormal concentration produces a detectable signal. Although the positron travels only a few millimeters before it collides with an electron, this annihilatory interaction produces two 511-keV photons, which travel through the patient in directions ~180° opposite to each other. The two photons are then captured simultaneously by the detectors, and the information is used to reconstruct the PET images (1–3).

PET Imaging Techniques

Prior to undergoing PET, patients are required to fast for several hours because elevated serum glucose levels can decrease cellular FDG uptake (4,5). In diabetic patients, the insulin dose should be adjusted so that the fasting blood glucose level is below the preferred level of 130 mg/dL (7.1263 mmol/L) prior to imaging. FDG is injected intravenously, and transmission scans are obtained to identify the area of interest. Multiple emission images are then obtained approximately 30–60 minutes after FDG injection (6). The data are recorded and can be reviewed in axial, sagittal, and coronal projections.

Abnormal FDG activity can be determined at visual inspection or with semiquantitative analysis by calculating a standardized uptake ratio. This is a ratio between the amount of activity within the lesion and the total injected dose and is normalized to the patient's weight. A standardized uptake ratio of less than 2.5 is generally thought to indicate a benign lesion (7,8).

FDG PET of Focal Pulmonary Abnormalities

Many focal pulmonary abnormalities remain indeterminate after conventional radiologic evaluation. Treatment depends on clinical history and likelihood of malignancy and traditionally consists of observation, transthoracic or transbronchial needle aspiration biopsy, or resection of the lesion. Unfortunately, these options are not always optimal in making the diagnosis. Nondiagnostic transthoracic or transbronchial needle aspiration biopsy is not uncommon in benign lesions (9), and up to 50% of resected indeterminate nodules prove to be benign (10,11). Thus, improvements in noninvasive imaging techniques that could help more accurately differentiate benign from malignant pulmonary lesions would have a tremendous impact on patient treatment.

FDG PET offers a new method of evaluating patients with pulmonary abnormalities, particularly if there is concern for malignancy. Although the sensitivity and specificity of PET are not optimal, this modality can often serve as a complement to conventional imaging. The need for PET depends on radiologic findings and the clinical situation, including potential treatment options. Not all patients with focal lesions must undergo FDG PET.

Once an abnormality has been detected, PET is very useful in differentiating benign from malignant lesions as small as 10 mm. The overall sensitivity, specificity, and accuracy of PET in identifying malignant lesions are 96%, 88%, and 94%, respectively (Fig 1) (1,7,12–15). Patients with positive findings at PET typically have a high probability of malignancy, although this depends on the patient population. In most cases, pulmonary lesions with increased FDG uptake should be considered malignant until proved otherwise. PET can also help in tumor staging (Fig 2) (16–18). However, false-positive results (ie, PET findings are abnormal but the lesion proves to be benign) can occur and have been reported in infectious and inflammatory processes such as active tuberculosis, histoplasmosis, and rheumatoid nodules (7,19–22).



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  		Figure 1a.   Non-small cell lung cancer in an asymptomatic 71-year-old woman. A prior anteroposterior chest radiograph (not shown) had demonstrated a small, 10-mm nodule in the left upper lobe. (a) Thoracic CT scan shows an indeterminate nodule 10 mm in diameter in the left upper lobe (arrow), thereby helping confirm the earlier radiographic finding. No other abnormalities were seen. (b) Axial PET scan demonstrates increased FDG uptake in the nodule (arrow), a finding that is suggestive of malignancy. No other areas of increased FDG uptake were identified. The lesion was resected and proved to be non-small cell lung cancer.

 


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  		Figure 1b.   Non-small cell lung cancer in an asymptomatic 71-year-old woman. A prior anteroposterior chest radiograph (not shown) had demonstrated a small, 10-mm nodule in the left upper lobe. (a) Thoracic CT scan shows an indeterminate nodule 10 mm in diameter in the left upper lobe (arrow), thereby helping confirm the earlier radiographic finding. No other abnormalities were seen. (b) Axial PET scan demonstrates increased FDG uptake in the nodule (arrow), a finding that is suggestive of malignancy. No other areas of increased FDG uptake were identified. The lesion was resected and proved to be non-small cell lung cancer.

 


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  		Figure 2a.   Non-small cell lung cancer in a 65-year-old man who presented with a cough. (a) Axial CT scan demonstrates a 2.5-cm mass in the right lower lobe. No other abnormalities were identified. (b) Coronal PET scan demonstrates increased FDG uptake in the right lower lobe mass (solid arrow). Two other unsuspected areas of increased uptake were found in the right humerus (arrowhead) and right first rib (open arrow). These findings proved to be stage IV non-small cell lung cancer.

 


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  		Figure 2b.   Non-small cell lung cancer in a 65-year-old man who presented with a cough. (a) Axial CT scan demonstrates a 2.5-cm mass in the right lower lobe. No other abnormalities were identified. (b) Coronal PET scan demonstrates increased FDG uptake in the right lower lobe mass (solid arrow). Two other unsuspected areas of increased uptake were found in the right humerus (arrowhead) and right first rib (open arrow). These findings proved to be stage IV non-small cell lung cancer.

 
When PET findings are negative, the probability of malignancy is very low (<5%) (14,23). False-negative results (ie, PET findings are normal but the lesion proves to be malignant) can occur with small (<1-cm) tumors and, rarely, with low-grade malignancies (Fig 3) (22,24,25). Patients with focal pulmonary abnormalities and no significant FDG uptake can be followed up radiologically at 3-month intervals. If the lesion grows, it is recommended that a tissue diagnosis be obtained (22,24,26). It is thought that the delay in diagnosis will not affect the patient's long-term outcome (27).



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  		Figure 3a.   Adenocarcinoma in an asymptomatic 72-year-old woman who presented for follow-up chest radiography for a lung nodule that had been discovered earlier. (a) Posteroanterior chest radiograph obtained in 1988 demonstrates a poorly defined, 8-mm nodule in the right upper lobe (arrow). (b) Follow-up chest radiograph obtained 10 years later demonstrates the right upper lobe nodule (arrow), which now measures approximately 18 mm. (c) Axial CT scan also demonstrates the nodule. (d) Axial PET scan demonstrates minimal uptake in the nodule (arrow). The nodule was resected and proved to be adenocarcinoma.

 


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  		Figure 3b.   Adenocarcinoma in an asymptomatic 72-year-old woman who presented for follow-up chest radiography for a lung nodule that had been discovered earlier. (a) Posteroanterior chest radiograph obtained in 1988 demonstrates a poorly defined, 8-mm nodule in the right upper lobe (arrow). (b) Follow-up chest radiograph obtained 10 years later demonstrates the right upper lobe nodule (arrow), which now measures approximately 18 mm. (c) Axial CT scan also demonstrates the nodule. (d) Axial PET scan demonstrates minimal uptake in the nodule (arrow). The nodule was resected and proved to be adenocarcinoma.

 


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  		Figure 3c.   Adenocarcinoma in an asymptomatic 72-year-old woman who presented for follow-up chest radiography for a lung nodule that had been discovered earlier. (a) Posteroanterior chest radiograph obtained in 1988 demonstrates a poorly defined, 8-mm nodule in the right upper lobe (arrow). (b) Follow-up chest radiograph obtained 10 years later demonstrates the right upper lobe nodule (arrow), which now measures approximately 18 mm. (c) Axial CT scan also demonstrates the nodule. (d) Axial PET scan demonstrates minimal uptake in the nodule (arrow). The nodule was resected and proved to be adenocarcinoma.

 


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  		Figure 3d.   Adenocarcinoma in an asymptomatic 72-year-old woman who presented for follow-up chest radiography for a lung nodule that had been discovered earlier. (a) Posteroanterior chest radiograph obtained in 1988 demonstrates a poorly defined, 8-mm nodule in the right upper lobe (arrow). (b) Follow-up chest radiograph obtained 10 years later demonstrates the right upper lobe nodule (arrow), which now measures approximately 18 mm. (c) Axial CT scan also demonstrates the nodule. (d) Axial PET scan demonstrates minimal uptake in the nodule (arrow). The nodule was resected and proved to be adenocarcinoma.

 
Although PET is more expensive than other imaging modalities, judicious use of this noninvasive procedure appears to be cost-effective in the evaluation of focal pulmonary lesions (28, 29). Decision analysis models have suggested that the use of computed tomography (CT) and PET in patients with suspected malignancy seems to be the most cost-effective and clinically useful strategy in treatment planning. It has been estimated that use of CT and PET together will save approximately $1,192 per patient compared with use of CT alone (28). However, observation appears to be the most cost-effective strategy in patients with a low pretest probability for malignancy (28).

Conclusions

PET has become an invaluable tool in the evaluation and treatment of patients with focal pulmonary abnormalities. It is more accurate than conventional imaging in characterizing indeterminate pulmonary lesions and distinguishing benign from malignant lesions. PET appears to be cost-effective and poses no significant risk to the patient if used in the appropriate clinical setting.

Footnotes

Abbreviations: FDG = 2-deoxy-2[fluorine-18]fluoro-D-glucose, PET = positron emission tomography

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