Diagnosis and Treatment
F-18 FDG Positron Emission Tomography in Lung Cancer
By Omer L. Burnett, Jr., MD
| Prognosis of lung cancer depends on the histologic type of the tumor, and on the clinical stage of the tumor at time of presentation. |
Lung cancer may be suspected on the basis of clinical signs and symptoms and may be detected and evaluated by chest X-rays, computed tomography (CT), and magnetic resonance imaging (MRI). Chest X-rays and CT are, at present, the most widely used imaging modalities for evaluation of chest nodules and masses. The solitary pulmonary nodule (SPN) is probably the most common radiographic presentation of lung cancer, with some 130,000 new SPN cases per year in the U.S., of which it is estimated that 50-60% will prove to be benign.2 Certain radiographic and CT characteristics (benign pattern of calcifications, e.g., "popcorn"; stability of size and appearance over two or more years; smooth tumor margins) of pulmonary nodules indicate that a lesion is probably benign. Others (large size, thick or nodular wall of a cavitary lesion, absence of calcifications, increasing size on follow-up, irregular margins) indicate malignancy.3,4 Radiographic and CT characteristics, although helpful, are not highly specific for malignancy. In the general population, only 20% or so of SPNs are malignant, with an even lower incidence of malignancy in geographic areas of endemic granulomatous disease.5
Of the large number of SPNs biopsied each year, with resulting morbidity and mortality, 20-40% prove to be benign.6 Significant cost and morbidity are, thus, borne by the larger subset of patients having benign SPNs, in the process of separating them from the smaller subset having SPNs which are lung cancers.
Prognosis of lung cancer depends: a) on the histologic type of the tumor, and b) on the clinical stage of the tumor at time of presentation. Optimal management of lung cancer depends on accurate staging of the disease. By currently accepted clinical and anatomic imaging (X-ray, CT, MRI) criteria, some 20-30% of lung masses encountered are classed as "operable" or "resectable." Of these, 5-7% are found at surgery to have more extensive cancers than expected and to have unresectable disease, and of those thought to have had curative surgery, 14% die within one year .7 The limitations of anatomic imaging techniques in staging lung cancer are widely recognized with respect to determining presence or absence of metastatic spread to the mediastinum, identifying metastatic sites in lymph nodes, demonstrating metastases distant from the primary tumor, and identifying sites of occult tumor. A recent, large, multi-institutional trial of staging of non-small-cell lung cancers (NSCLC) indicated an overall sensitivity for CT of 52% and specificity of 69%; for MRI, sensitivity was 48% and specificity, 64%.7
Positron Emission Tomography (PET), using the radiolabeled glucose analog radiopharmaceutical F-18 FDG (2-[18F]fluoro-2-deoxy-d-glucose) has been in use for a number of years in some academic medical centers and has now become more widely available due to the availability of commercially built PET imaging systems and the entry into the medical marketplace of commercial operators of cyclotron sites capable of delivering unit doses of F-18 FDG within many locations in the U.S. and worldwide. A considerable body of experience has been built up over recent years, in application of F-18 FDG PET to the evaluation of solitary pulmonary nodules10, 11, 12, 13 and preoperative staging of lung cancers,14,15,16,17 as well as to demonstration of recurrences of lung cancer after surgery/therapy,18, 19, 20 and investigation of malignant pleural disease.21 Various studies, including those referenced above, have indicated that the average sensitivity of F-18 FDG PET in detecting malignancy in SPNs is about 95%, with specificity of about 88%; for detection of primary lung cancer, sensitivity is about 96%, and specificity about 88%; and for detecting metastatic involvement in lung cancer, sensitivity is about 88%, and specificity around 91%. However, although the ability of F-18 FDG PET to demonstrate sites of malignancy and to distinguish between benign and malignant lesions is high, it is by no means perfect.
F-18-FDG PET may, for example, demonstrate only mildly increased uptake or even negative results in bronchioloalveolar carcinomas. False-positive results may occur in some infectious and inflammatory processes, including sarcoidosis, histoplasmosis, atypical mycobacterial infections, and active tuberculosis.
With that caveat in mind, F-18 FDG PET, especially when used in conjunction with CT, can contribute greatly to the accuracy of lung cancer patients' evaluation.
It can reduce the number of non-beneficial surgical procedures, may demonstrate that patients felt to be inoperable on the basis of anatomic criteria may in fact be eligible for curative surgery, can direct earlier and more beneficial institution of chemotherapy and/or radiation therapy in some patients, and may reduce the overall financial costs of lung cancer management.
Malignant neoplastic cells, including those of most lung cancers, tend to use glucose as a major metabolic substrate and to exhibit higher metabolic rates (and higher rates of glucose utilization) than do most normal cells. F-18 FDG is a glucose analog, in which a radioactive fluorine atom (F-18) is substituted for an oxygen atom at one position on the glucose molecule. F-18 FDG is taken into cells by the same active transport processes within the cell membrane as glucose. Malignant cells tend to exhibit an increased density and number of cellular membrane surface transport proteins, which facilitate active transport of glucose into the cells. Once inside the cell, F-18 FDG, like glucose, undergoes phosphorylation by hexokinase. However, the phosphorylated form of FDG does not undergo further metabolism, and remains in the cell, only slowly diffusing out of it.
Fluorine-18, to which the glucose moiety is attached, undergoes radioactive decay, with a half-life of 109 minutes. Decay of F-18 results in emission of a positron, which interacts with an electron, resulting in two, 511 keV annihilation photons, which are emitted at 1800 from each other and which may be detected by positron emission tomography imaging systems (i.e., PET cameras). F-18 FDG positron emission tomography is thus able to provide a regional and local "map" of sites of glucose utilization throughout the body, in which areas of high rates of glucose metabolism (such as many malignant neoplasms) appear more intense than areas within which rates of glucose utilization are lower.
 Figure 1 Coronal whole-body F-18 FDG image, mapping normal physiologic metabolic activity in visualized parts of the brain, myocardium, liver, spleen, kidneys, bladder, and (less intensely) GI tract and skeletal muscle. |
Normal F-18 FDG images (See Figure 1) demonstrate intense uptake
of FDG in the brain; variably intense or very little uptake in the
myocardium (depending on whether the myocardium is utilizing glucose or fatty acids
as its energy substrate at the time of the study); liver; spleen; kidneys; bladder;
and, often to a variable degree, skeletal muscle; GI tract; and, possibly, thyroid.
The radiation dose received by the patient during an F-18 FDG study is, partly because of the very short half-life of F-18, quite modest and is less than that resulting from many common radiologic procedures. For the usual 10-15 mCi diagnostic dose of F-18 FDG, the whole body absorbed radiation dose is on the order of 0.5 rad, which compares favorably to the approximately 1.5 rad whole body absorbed radiation dose for an X-ray lumbar spine series, and to the approximately 1.9 rad dose for an abdominal CT study.8, 9 Small cell carcinoma of the lung is an aggressive neoplasm, which typically has spread beyond the primary tumor site by the time of diagnosis. Figures 2a and 2b on this page depict a previously essentially asymptomatic patient who developed cough, with a right upper lung zone mass seen on chest X-ray and CT of the chest. F-18 FDG PET study gave evidence of widespread disease in both hemithoraces, as well as the abdomen. Transbronchial biopsy of the large right upper lung zone mass yielded the histologic diagnosis of small cell carcinoma. Biopsy of the large mass in the upper pole of the
left kidney resulted in diagnosis of metastatic small
cell carcinoma. The patient received radiation and
chemotherapy, but did not undergo surgery. |
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Figure 2a and 2b (left) Axial CT sections for a patient through the chest (A, shown at left) and upper abdomen (B) |
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Figure 2a, showing axial CT sections through the chest (A) and upper abdomen (B) for this patient, show a large mass (noted by arrows) in the upper right lung. The lower image (B) shows a sizable mass (noted by arrows) in the upper pole of the left kidney.
Figure 2b shows coronal images from F-18 FDG PET study of the same patient as in Figure 2a.
In the scan below (Figure 2c), large, intensely hypermetabolic masses in the right upper lung and upper pole of left kidney (both areas noted by arrows) correspond to the masses seen on CT.
The mass in the left kidney proved to be metastatic small cell
carcinoma. In the two lower images (Figures 2c and
2d), small hypermetabolic foci (small arrows) area consistent
with contralateral pulmonary metastases.
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Figure 2c and 2d (left) Coronal
images from F-18 FDG PET study of the |
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Patient presented with a 3 cm. RML mass on chest
X-ray (arrows, A). Right lung mass is seen on CT study
of the thorax (arrows, B), with no evidence of
mediastinal invasion.
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Figure 3a and 3b (above) Chest X-ray and CT thorax study. Figure 3c (left) Whole-body image An F-18 FDG PET, coronal whole-body image is seen here in Figure 3c. A single, intensely hypermetabolic abnormality is demonstrated in the right lung, with physiologic FDG localization in other areas. The patient underwent surgery, and the pathology showed non-small carcinoma of the right middle lobe. Mediastinal nodes were negative for metastasis. |
