© 2004 Foundation for Promotion of Cancer Research
The Use of Dual Phase 201Tl SPECT for Differentiating Pulmonary Malignancies from Benign Lesions
1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, 2 Division of Thoracic Surgery, Department of Surgery, 3 Department of Pathology and 4 Department of Nuclear Medicine, China Medical University Hospital, Taichung, Taiwan
For reprints and all correspondence: Wu-Huei Hsu, Division of Pulmonary and Critical Care Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan. E-mail: hsuwh{at}www.cmuh.org.tw
Received March 2, 2004; accepted June 1, 2004
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Abstract |
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 TOP Abstract INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: This study examines the usefulness of thallium-201 single photon emission computed tomography (201Tl SPECT) in differentiating pulmonary malignancies from benign lesions by using dual phase 201Tl scintigraphy.
Methods: One hundred and six patients with thoracic lesions and confirmed diagnoses were assessed by 201Tl chest SPECT examinations; of these 106 enrolled thoracic lesions, 59 were malignancies and 47 were benign lesions. Dual phase 201Tl SPECT was performed with an early image acquired at 10–20 min and a delayed image at 2–3 h after intravenous injection of 2–3 mCi of 201Tl. The results of 201Tl SPECT images were classified as either malignant or benign lesions by visual interpretation: the lesion was interpreted as positive for malignancy if the uptake of 201Tl in the lung lesion in the delayed phase was increased or persistent as compared with that in the early phase image; otherwise, it was considered as a benign lesion. Simultaneously, the traditional method of retention index (RI) was also calculated to help in the differential diagnosis of pulmonary lesions. Then, both methods of dual phase 201Tl SPECT, visual reading and traditional RI, were compared to differentiate pulmonary malignancies from benign lesions.
Results: Analyzing the image results, we found that dual phase 201Tl SPECT could differentiate pulmonary malignancies from benign lesions with a sensitivity of 83%, a specificity of 91% and an accuracy of 87%. Moreover, by using the traditional RI method of 201Tl SPECT, it could differentiate pulmonary malignancy from benign lesions with a sensitivity of 79.3%, a specificity of 80.8% and an accuracy of 80%.
Conclusions: We conclude that using dual phase 201Tl SPECT with visual interpretation is a simpler and potentially more effective method for differentiating pulmonary malignancies from benign lesions, with results compatible with the traditional RI method of 201Tl SPECT.
Key Words: thallium-201 • SPECT • lung cancer • pulmonary lesions • retention index
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INTRODUCTION |
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TOPAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The differential diagnosis of lung cancer from a benign lesion is critically important in the management of an abnormal pulmonary lesion found on a chest X-ray. The process of diagnosing lung cancer mostly begins when a chest X-ray arouses suspicion of a possible lesion. However, it is often unreliable to diagnose lung cancer by chest X-ray image alone, particularly when a time series of chest X-ray films is not available, a common clinical situation that physicians frequently encounter.
Computed tomography (CT) can assess thoracic lesions with more information in detail than a chest X-ray, but it is still an imaging modality and may be limited in mass-like pulmonary lesions (1–4). Several procedures will then be needed to confirm the diagnosis, such as sputum cytology, transbronchial lung biopsy and image (fluoroscopy, ultrasound or CT)-guided percutaneous needle biopsy. However, the sputum cytology is often negative; transbronchial lung biopsy and image-guided transthoracic needle biopsy are somewhat invasive and depend on the operator's skill and the cytopathologist's experience. Among the imaging modalities used in chest medicine, 201Tl lung scan is a non-invasive imaging modality and, as reported in the literature (5), provides another piece of useful information in the differential diagnosis of pulmonary lesions.
Accumulation of 201Tl in cancer cells has already been reported (6). The application of 201Tl lung scan with the retention index (RI) method has been used to diagnose various types of cancer, to establish its relationship with the proliferation of cancer cells and potentially to predict the response to chemotherapy (5–16). However, its practical application has not yet been determined. Here, we report our results and experience using dual phase 201Tl chest SPECT images in an attempt to differentiate thoracic malignancies from benign lesions.
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SUBJECTS AND METHODS |
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TOPAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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PATIENTS
From February 1, 2002 to February 1, 2003, 106 patients with pulmonary lesions on their chest X-ray were prospectively studied by 201Tl SPECT. The enrolled patients comprised 82 men and 24 women, with the mean age of men 62.20 years (range 22–89) and that of women 60.43 years (range 34–88). The final diagnoses were 59 cancers and 47 benign lesions.
The 59 cancers consisted of 56 primary lung cancers and 3 metastatic lung cancers. The primary 56 lung cancers comprised squamous cell carcinoma (n = 21), adenocarcinoma (n = 29), small cell lung cancer (SCLC, n = 2), poorly differentiated carcinoma with non-small cell lung cancer type (NSCLC, n = 1), leiomyoscarcoma of the lung (n = 1) and primary lung cancers confirmed by chest CT with compatible clinical condition for follow-up of 6 months, and with brain metastasis eventually (n = 2). The three metastatic lung cancers comprised transitional cell carcinoma of the kidney (n = 1), cervical squamous cell carcinoma (n = 1) and olfactory neuroblastoma (n = 1). The 47 benign pulmonary lesions consisted of tuberculosis (n = 22), pneumonia (n = 13), empyema (n = 2), lung abscess (n = 3), organizing pneumonia (n = 2), sclerosing hemangioma (n = 1), Wegener's granulomatosis (n = 1), pneumoconiosis (n = 1), angiomyolipoma (n = 1) and infective cyst (n = 1). The clinical diagnosis, diagnostic methods and tumor sizes of 106 pulmonary lesions are listed in Table 1 in detail (16).
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All patients enrolled were arranged to receive dual phase 201Tl chest SPECT after informed consent was obtained.
DUAL PHASE 201TL CHEST SPECT
The patient was positioned supine on the imaging table with the chest strapped in order to prevent movement. Dual phase 201Tl chest SPECT was performed with a Vertex dual-head gamma camera (ADAC, Milphas, CA) equipped with low-energy, high-resolution collimators 10–20 min and 2–3 h after 2–3 mCi (74–111 MBq) of 201Tl were injected intravenously. Data were collected from 64 projections over 360° (180° for each head) in 64 x 64 matrices, with an acquisition time of 20 s per projection under a photon peak window of 70 Kev ± 10% (5,9). Reconstruction of the image was performed with attenuation correction using a Butterworth filter (17), and with a cut-off frequency of 0.35 per cm and an order of 5. Then, images of one pixel thickness were obtained in the sagittal, coronal and transverse planes for visual interpretation.
VISUAL INTERPRETATION OF DUAL PHASE 201TL CHEST SPECT
The dual phase images were simultaneously examined in series order under synchronization by landmark of heart, liver or thyroid. When the lesion was defined under the synchronized dual phase comparable area, we then compared the accumulation of 201Tl in the lesion with that in the surrounding lung tissue. If the uptake of 201Tl in the lesion in the delayed phase was increased or persistent as compared with that in the early phase image, the 201Tl SPECT for the lesion was defined as positive for malignancy; otherwise, it was defined as a benign lesion.
THE TRADITIONAL RI METHOD OF 201TL SPECT
As in the procedure above, when the lesion was arranged synchronously, the region of interest (ROI) was carefully selected based on dual phase comparable area; meanwhile, the counterpart ROI in the symmetrically contralateral normal lung field (i.e. background) was assigned. The mean voxel counts of the ROI, i.e. mean value of lesion (Vle) and mean value of background (Vbg), for the lesion and background were recorded; then the lesion value divided by the background value obtained the uptake ratio of the lesion in early and delay phase, i.e. early uptake ratio (EUR) and delay uptake ratio (DUR). Finally, we calculated the uptake ratios of the dual phase to obtain the RI (i.e. RI = [(DUR – EUR)/EUR] x 100%).
STATISTICAL ANALYSIS
After collecting all the data from the 201Tl SPECT examination for the 106 patients enrolled, we then analyzed the results and calculated the sensitivity, specificity and accuracy of the 201Tl chest SPECT to differentiate the pulmonary malignancies from the benign lesions (18). Both the methods of visual interpretation and RI of dual phase 201Tl SPECT for differentiating the pulmonary malignancies from benign lesions were used and compared. Moreover, pulmonary tuberculoses, often mimicking lung cancers with delayed diagnosis clinically, were also analyzed further.
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RESULTS |
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DEMOGRAPHIC DATA
The basic data of the 106 patients enrolled and confirmed diagnoses with compatible clinical conditions of 106 thoracic lesions are summarized in Table 1. In the 59 malignant lesions, 49 cancers showed increased or persistent uptake in the delayed phase of 201Tl chest SPECT (Fig. 1). Nevertheless, there were still 10 patients with primary lung cancers revealing decreased or even no uptake in the delayed phase of 201Tl SPECT. Interestingly, we found that four cases among the 10 false-negative results had prominent central necrosis with decreased or no uptake in the delayed phase of 201Tl SPECT (Fig. 2).
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In the 47 benign lesions, 43 showed decreased or no uptake in the delayed phase of 201Tl chest SPECT (Fig. 3). However, there were also still four lesions revealing persistent uptake in the delayed phase of 201Tl SPECT scans, including two pneumonia, one organizing pneumonia and one tuberculosis. The four lesions may be due to an acute and active inflammatory process.
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RESULTS OF THE DUAL PHASE 201TL SPECT
Analyzing the results of the 201Tl chest SPECT in 106 patients, we found that the dual phase 201Tl chest SPECT is useful in differentiating the pulmonary malignancies from the benign lesions (as shown in the results in Table 2 in detail). The dual phase 201Tl chest SPECT with simple visual interpretation method could differentiate pulmonary malignancies from benign lesions with a sensitivity of 83%, a specificity of 91% and an accuracy of 87%. Even the 22 cases of pulmonary tuberculosis, often a misdiagnosis of lung cancer clinically, were excluded; the results were still promising with a sensitivity of 83%, a specificity of 88% and an accuracy of 84%.
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RESULTS OF THE CONVENTIONAL RI 201TL SPECT
Simultaneously, we also used the traditional RI method to assess the ability of 201Tl SPECT to differentiate the pulmonary malignancies from benign lesions. As the cut-off value 20% of RI was set based on the best point from receiver operating characteristic curves, we found the RI method had a sensitivity, specificity and accuracy of 79.3%, 80.8%, and 80%, respectively, to differentiate malignancies from benign lesions (as shown in Table 2). When tuberculoses were excluded, the traditional RI method had sensitivity 79%, specificity 84% and accuracy 81%.
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DISCUSSION |
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TOPAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Thallium-201 has been used to detect defects in myocardial perfusion for more than 30 years. The physical and biomedical properties of thallium are comparable to those of potassium ion, both of which are actively transported into the cell by Na-K-ATPase (19–21). The accumulation of 201Tl in pulmonary neoplasms was a coincidental finding by Cox et al. (22) when a patient with neoplasm of the lung received thallium scans for myocardial infarction. Thereafter, several studies were undertaken to test the usefulness of 201Tl chest SPECT to differentiate lung cancers from benign lesions, but the results still remain controversial (5,9).
Reviewing the published literature, we know 201Tl chest SPECT may have a diagnostic value to differentiate lung cancers from benign lesions by using the imaging 201Tl uptake ratio, often retention ratio [((delayed uptake – early uptake) ÷ early uptake) x 100%] used and reported with an accuracy around 70–90% (5,23–25). In our present study and results, we just simplified the interpretation method by using the simple dual phase visual interpretation and obtained the same promising results of sensitivity and specificity as reported in the literature. Moreover, pulmonary tuberculoses were often interpreted as malignancies in previous reports and limited the value of 201Tl SPECT in its clinical application (6,24). In our series, however, we found the simple dual phase visual interpretation method of 201Tl chest SPECT also to be promising in the differentiation of pulmonary malignancies from benign lesions, including the differentiation between pulmonary malignancies and tuberculosis. Of course further larger studies are required to confirm our results. From our experience, we found that in 201Tl chest SPECT images tuberculosis often appeared less compact than malignancies, although both tuberculosis and malignancy can present with persistent uptake in delayed phase, which may in part explain why the result of visual interpretation is somewhat better than that of the RI in our study.
In our study, we used a simple visual interpretation of 201Tl chest SPECT to screen pulmonary lesions and obtained a good result. Analyzing the false-negative imaging results in 10 patients with primary lung cancers, four patients showed weak or no 201Tl uptake in SPECT scans (Fig. 2C), which could be due to massive tumor necrosis as shown in thoracic CT images (Fig. 2A), and two patients with prominent central necrosis were definitely confirmed by surgical lung resection. Among the remaining six patients with false-negative 201Tl SPECT scans, three had a smaller tumor size ranging from 18 to 24 mm in diameter. Therefore, a small pulmonary nodule may be somewhat limited in using 201Tl chest SPECT to differentiate the pulmonary malignancies from benign lesions. Regarding the four benign lesions misinterpreted as lung cancers, the strong uptake of 201Tl chest SPECT could be due to active inflammation or infection as shown in the clinical condition and a series of chest X-ray findings.
Two factors have an impact on the accumulation of 201Tl in tissues: regional blood flow and cell viability. To assess the effect of cell viability on the uptake of 201Tl, immunohistochemical studies and monoclonal antibodies may be needed to confirm cell viability, which could only be performed by resected specimens (11,12). Regarding the assessment of regional blood flow, our cases showed massive tumor necrosis and weak 201Tl uptake (Fig. 2), which had not been clearly demonstrated in previous reports. However, our results confirmed regional blood flow as the significant factor to assess the 201Tl uptake in viable cells in pulmonary lesions.
In conclusion, the visual interpretation of dual phase 201Tl chest SPECT is a simple and useful method in differentiating pulmonary malignancies from benign lesions, and from our experience the results are promising. The method of dual phase 201Tl chest SPECT also shows compatible results with the traditional RI method of 201Tl SPECT. It is worthy of wide clinical application in the differential diagnosis of pulmonary malignancies and benign lesions. However, interpretation should certainly still be left to experienced experts. As imaging modalities and computer technologies progress rapidly, the fusion images of axial CT on SPECT may further improve the accuracy of 201Tl chest SPECT in pulmonary malignancies.
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