The utility of [sup.99m]Tc depreotide compared with F-18 fluorodeoxyglucose positron emission tomography and surgical staging in patients with suspected non-small cell lung cancer – clinical investigations
Daniel Kahn
Study objectives: The findings from conventional imaging modalities, such as chest CT, are frequently unreliable in patients with lung cancer. This study was designed to compare the relative diagnostic accuracies and utility of the two most widely used functional imaging examinations, F-18-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) and [sup.99m]Tc depreotide scintigraphy, for the diagnosis and staging of lung cancer.
Design: Prospective, experimental investigation.
Setting: Academic medical center.
Patients: One hundred sixty-six subjects with suspected lung cancer were enrolled in the study.
Interventions: Whole-body and single-photon emission CT imaging of the chest was performed after IV administration of [sup.99m]Tc depreotide. Attenuation-corrected FDG PET imaging was performed after IV administration of FDG. Image findings were compared with the biopsy results or clinical follow-up.
Measurements and results: In 157 subjects with evaluable lung lesions, the sensitivities and specificities for detecting malignant disease (95% confidence intervals) of FDG PET are 96% (90 to 98%) and 71% (54 to 85%), and of [sup.99m]Tc depreotide are 94% (88 to 98%) and 51% (34 to 68%). In the 139 subjects with available complete staging data, FDG PET correctly staged 76 of 139 patients (55%), and [sup.99m]Tc depreotide correctly staged 63 of 139 patients (45%).
Conclusions: The sensitivity for detection of lung cancer in the primary lesion is equally high for FDG PET and [sup.99m]TC depreotide. The specificity is superior for FDG PET. The staging accuracy of FDG PET and [sup.99m]Tc depreotide is similar, but when read with the chest CT neither scintigraphic examination is sufficiently accurate to stage patients with non-small cell lung cancer.
Key words: lung cancer; positron emission tomography; scintigraphy: [sup.99m]Tc depreotide
Abbreviations: AJCC-ISS = American Joint Committee on Cancer/International Staging System; CI = confidence interval; FDG = F-18-2-fluoro-2-deoxyglucose; PET = positron emission tomography; SPECT = single-photon emission CT; SUV = standardized uptake value
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Conventional imaging methods, such as chest CT, continue to play important roles in the detection of lung cancer and in tumor staging, but they often fail to distinguish between malignant and nonmalignant tumors in the lung or metastasis to the mediastinum. (1-6) Definitive diagnosis and staging have traditionally depended on invasive techniques. However, even invasive procedures such as bronchoscopy and transbronchial or transthoracic biopsy have sensitivities of < 80% in certain settings, (7,8) and may be associated with significant complications. (9)
The development of functional imaging examinations represents a significant advance in the diagnostic assessment of patients with lung cancer. F-18-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) is one such examination that takes advantage of increased glucose utilization by tumor cells to differentiate malignant from nonmalignant lesions. (10,11) A recent summary (12) of several studies involving > 2,000 patients reports that the sensitivity and specificity of FDG PET in the primary lung lesion were 96% and 74%, and that the sensitivity and specificity for the detection of tumor-bearing thoracic lymph nodes were 83% and 89%, respectively.
More recently, other studies (13-17) have reported that somatostatin analog scintigraphy can accurately detect lung cancer. [sup.99m]Tc depreotide (NeoTect; Berlex Laboratories; Montville, NJ), one radiolabeled somatostatin analog, has been shown to accurately identify malignant solitary pulmonary lesions. (18) To date, there have been no trials reporting the capacity of [sup.99m]Tc depreotide to stage lung cancer, or whether this newer, more widely available agent can provide the same information as FDG PET. The purpose of the present study was to directly compare the diagnostic accuracies of FDG PET and Tc-99m depreotide for diagnosis and staging patients suspected of having lung cancer.
MATERIALS AND METHODS
Patients
After signing an informed consent statement approved by our Institutional Review Board for the study of human subjects, 166 subjects (48 women and 118 men; median age, 68 years; range, 40 to 87 years) who had abnormal chest CT scan results and were suspected of having operable and potentially curable lung cancer were prospectively enrolled into the study. All were scheduled to have a definitive diagnosis made and tumor staging performed by surgical intervention.
FDG PET Imaging and Interpretation
Each patient underwent a FDG PET examination as part of their routine evaluation. After a 4-h fast, each patient received 10 to 15 mCi (370 to 555 megabecquerels) of FDG IV. All patients underwent imaging 60 min following FDG injection using a GE 4096 Plus PET (GE Medical Systems; Milwaukee, WI) scanning from the base of the brain to the level of the proximal thighs in multiple bed positions. This unit is a stand-alone PET unit (not a PET-CT device). Transmission scans using a [sup.68]Ge pin source were performed on all patients after the acquisition of the FDG, from which attenuation correction factors were calculated and used to correct the FDG emission data. The attenuation-corrected emission data were reconstructed with an iterative reconstruction algorithm using ordered subsets expectation maximization.
Images were evaluated separately and independently by two nuclear medicine specialists (each blinded to the [sup.99m]Tc depreotide results) in three orthogonal planes on the computer monitor and compared with the chest CT scan. Differences of opinion were resolved by a third reader. Interpretation of the primary lesion was based on inspection of the attenuation-corrected images according to standard practice and the methods published by Lowe and coworkers. (11,19) If the activity in the lesion was greater than the activity seen in the mediastinum, it was considered positive for malignancy. In the hilum and mediastinum, focal activity that was greater than surrounding “background” mediastinal activity was interpreted as malignant spread. Abnormalities were assigned (and then later correlated with the surgical and biopsy reports for comparison) to either the right or left superior (stations 1 and 2), inferior (stations 3, 4, 5, and 6) or subcarinal (stations 7 and 8) mediastinal region(s) and to the right or left hilar (stations 10 to 14) region(s). Focal increases in activity seen in locations not accounted for by the norlual sites of FDG biodistribution were interpreted as extrathoracic metastatic disease. The FDG PET findings were then used to assign a tumor stage based on the American Joint Committee on Cancer/ International Staging System (AJCC-ISS). (20,21)
[sup.99m]Tc Depreotide Imaging and Interpretation
[sup.99m]Tc depreotide examinations were performed within 3 weeks of the FDG PET examination. Vials of [sup.99m]Tc depreotide containing 50 [micro]g of the peptide were reconstituted according to package insert instructions. Twenty mCi (740 megabecquerels) of Tc-99m depreotide was injected IV, and whole-body anterior and posterior images were obtained 60 min later. Single-photon emission CT (SPECT) of the chest, including the upper abdomen with the adrenal glands, was then performed starting at 90 min after injection. Imaging was performed with a dual-detector gamma camera equipped with low-energy, high-resolution collimators (Prism 2000; Philips Medical Systems; Cleveland, OH). Two separate sets of images were generated from the data set of each examination, one optimized for the thorax, and the other for visualization of the adrenal glands.
All images of the thorax and upper abdomen were evaluated (blinded from the FDG PET examination) separately and independently by two nuclear medicine physicians on the computer monitor of the camera in three orthogonal planes. The chest CT scan was visually compared with the [sup.99m]Tc depreotide examination at the time of interpretation. Differences of opinion were resolved by a third reader. Focal areas of increased uptake compared with surrounding lung in the region of the CT scan abnormality were considered positive for malignancy; uptake less than or equal to adjacent or surrounding lung was interpreted as benign disease. In the hilum and mediastinum, focal activity that was greater than surrounding “background” mediastinal activity was interpreted as malignancy, with regional location determined in the same fashion as for the FDG PET examination. Focal increases in activity seen in locations unaccounted for by the normal biodistribution of the agent were interpreted as extrathoracic metastatic disease. As with the FDG PET interpretations, the [sup.99m]Tc depreotide findings were used to stage the patients according to the AJCC-ISS. (20,21)
Statistical Analysis
Sensitivity, specificity, and positive and negative predictive values with 95% confidence intervals (CIs) were computed in the standard fashion. The McNemar test of symmetry for nonindependent frequencies was used to test for significant differences between the sensitivities and specificities of the imaging methods. (22) A Student t test was used to assess significant differences between two methods of FDG PET interpretation in the primary lesions; p < 0.05 was considered significant.
RESULTS
Primary Lung Lesion
Nine of the 166 subjects (5%) were excluded from analysis of the primary lesion because metastatic disease was proven before the biopsy of this lesion (n = 3), surgery was medically contraindicated (n = 2), or the patient refused any procedures to evaluate the lung lesion (n = 4). In the 157 subjects with complete data available, there were 122 malignant and 35 benign primary lesions. The median lesion size (average of the two longest dimensions on the chest CT) was 2.2 cm (range, 0.5 to 10.5 cm). Histopathology was used to determine the status in all 122 malignant lesions and in 23 of the benign lesions. Tissue for diagnosis was obtained by bronchoscopy (n = 48), fine-needle aspiration (n = 11), or open biopsy (n = 86). The benign nature of the lesion was confirmed with clinical follow-up in 12 subjects. In six subjects, the lesions were smaller or showed no change in size following repeat chest CT or chest radiograph obtained for at least 12 months (range, 12 to 17 months). The lesions resolved entirely in six other subjects.
The sensitivity, specificity, and positive and negative predictive values with 95% CIs of FDG PET and [sup.99m]Tc depreotide for the diagnosis of the primary lung lesion in the 157 subjects are shown in Table 1. The sensitivities of the two examinations are not statistically different, but the specificity of FDG PET was greater than that of [sup.99m]Tc depreotide (McNemar test, p < 0.02). There were five false-negative FDG PET scan findings (lesion sizes, 0.5, 0.75, 1.5, 2, and 3 cm) and seven false-negative [sup.99m]Tc depreotide scan findings (lesion sizes, 0.5, 0.75, 1.2, 1.5, 1.5, 1.5, and 4 cm). The results of both studies were false-negative in only two patients (lesion sizes, 0.5 cm and 0.75 cm, respectively). There were six cases of bronchoalveolar carcinoma in our series, three of which were undetected by FDG PET and two undetected by [sup.99m]Tc depreotide. There were no subjects with carcinoid tumors in our series. In the 13 subjects with surgically proven granulomatous disease, results of both FDG PET and [sup.99m]Tc depreotide were false-positive in 5 subjects (in 4 of these 5, both test results were false-positive). Examples of true-positive lesions with [sup.99m]Tc and FDG are shown in Figures 1, 2.
[FIGURES 1-2 OMITTED]
For comparison, standardized uptake values (SUVs) were available in 121 malignant lesions and the same 35 benign lesions. In the malignant lesions, the mean SUV [+ or -] SD was 9.31 [+ or -] 6.14; in the benign lesions, it was 1.67 [+ or -] 1.55. These values are significantly different (Student t test, p < 0.0001). Using a threshold SUV of 2.5 (< 2.5 is benign, [greater than or equal to] 2.5 is malignant), the sensitivity and specificity of FDG PET for malignancy in the primary lesion were 90% and 80%, respectively.
Combining the results of both tests and interpreting a lesion as malignant when either scan result is positive yields a sensitivity and specificity of 98% (95% CI, 96 to 100%) and 49% (95% CI, 32 to 66%), respectively. The combined test sensitivity is not significantly different from FDG PET alone (McNemar test, p = 0.08), but is significantly greater than [sup.99m]Tc depreotide (McNemar test, p = 0.02). The specificity of combining the examinations is significantly lower compared with FDG PET (McNemar test, p = 0.005) but not different from [sup.99m]Tc depreotide (McNemar test, p = 0.32).
Hilar and Mediastinal Lymph Nodes
Complete results of mediastinal and hilar lymph node stations were available in 128 of the 166 patients (77%). Results were obtained by systematic sampling of the paratracheal and hilar nodal stations in 108 of these subjects (mediastinoscopy/intraoperative sampling during thoracotomy), including 14 patients in whom the primal lesion later proved to be benign. The remaining 20 patients with benign primary, lesions were not surgically staged but were classified as negative (NO). The hilum and mediastinum results in 38 patients with cancer were eliminated because they refused surgery or it was medically contraindicated (n = 12), had inoperable disease including stage IV (n = 19), had metastatic tumor to the lung from another organ (n = 4), or had inadequate tissue sampling performed (n = 3). In the 128 subjects, the node stage was as follows: NO (n = 97), N1 (n = 6), N2 (n = 19), and N3 (n = 6).
The sensitivity, specificity, and predictive values in the hilum and mediastinum of the two examinations compared to histopathologic results are shown in Table 1. No statistically significant difference was detected between the taro examinations (McNemar test, p = 0.10 sensitivities, p = 0.16 specificities).
Whole-Body Final Stage
A final pathologic stage was assigned according to the AJCC-ISS (20-21) in 139 subjects. In 134 of 139 patients, biopsy results determined the final stage, in five patients, surgery was not indicated as metastatic lung cancer was confirmed using MRI (n = 3), CT (n = 1), or bone scintigraphy (n = 1). Final staging data were unavailable in 27 of the 166 subjects (16%), as patients refused surgery (n = 21), were unavailable for follow-up (n = 2), or were proven to have metastatic disease to the lung (n = 4) from another organ (uterine, bladder, colon, and kidney). For the imaging stage, when FDG PET or [sup.99m]Tc depreotide results were positive in the primary, lesion, the chest CT scan was used to determine the tumor (T1-4) stage. N1, N2, and N3 disease as well as distant lesions (M1) were determined directly and only from the respective nuclear medicine scan.
The relationships between FDG PET, [sup.99m]Tc depreotide, and final stage are depicted in Tables 2, 3. FDG PET correctly staged 76 of 139 cases (55%), and [sup.99m]Tc depreotide correctly staged 6:3 of 1:39 cases (45%). When either FDG PET or [sup.99m]Tc depreotide misstaged cases, the other scan usually did not correctly stage the tumor (Tables 4, 5).
Surgical (Final Stage Less Than IIIB) vs Nonsurgical (Final Stage IIIB or IV) Disease
We also evaluated the ability of each scan to separate surgical (n = 112) from nonsurgical (n = 27) disease. To detect nonsurgical disease, FDG PET had a sensitivity of 63% (95% CI, 42 to 80%) and a specificity of 84% (95% CI, 76 to 90%), whereas [sup.99m]Tc depreotide had a sensitivity of 52% (95% CI, 32 to 71%) and a specificity of 86% (95% CI, 78 to 91%). Neither the sensitivities (McNemar test, p = 0.32) or specificities (p = 0.55) of these two modalities differed significantly. To detect nonsurgical disease, chest CT alone had a sensitivity of 92%, (95% CI, 85 to 96%) and a specificity of 33% (95% CI, 17 to 54%).
Distant Sites of Abnormal [sup.99m]Tc Depreotide or FDG PET Uptake
There were 22 patients with distant sites of abnormal uptake seen (imaging stage IV) with either FDG PET alone (n = 10), [sup.99m]Tc depreotide alone (n = 5), or both scans (n = 7). In 8 of these 22 patients, stage IV disease was confirmed before thoracotomy. In three of the eight patients, the sites of distant disease had already been detected with CT or bone scans prior to FDG PET or [sup.99m]Tc depreotide imaging. In the remaining 14 of 22 stage IV patients, thoracotomy with curative intent was performed because the positive FDG PET or [sup.99m]Tc depreotide findings could not be confirmed before surgery. Clinical follow-up was performed in this group. After clinical follow-up, disease was confirmed in 2 of 14 patients by bone scan and CT scans 1 month and 5 months after surgery, respectively. False-positive findings were seen in 9 of the 14 patients based on biopsy results in 2 patients and clinical follow-up (range, 6 to 31 months) in 7 patients. In 3 of the 14 patients, the scan findings could not be confirmed as the patients were unavailable for follow-up. Therefore, 5 patients before thoracotomy and 2 patients after thoracotomy (total of 7 patients [5%]) of 139 patients had otherwise unsuspected disease first detected with [sup.99m]Tc depreotide alone (n = 1), FDG PET alone (n = 2), or both (n = 4). Nine of 139 patients (6%) with abnormal distant sites detected only by [sup.99m]Tc depreotide (n = 4), FDG PET (n = 4), or both (n = 1) had false-positive findings.
DISCUSSION
Noninvasive testing results from patients with suspected lung cancer are frequently unreliable. Conventional imaging techniques have a limited diagnostic accuracy since interpretation relies principally on lesion size and other nonspecific findings.) (3) For this reason, newer imaging methods that do not rely solely on lesion size have been evaluated in patients with lung cancer.
We have found that FDG PET and [sup.99m]Tc depreotide scans are equally sensitive for the detection of lung cancer at the primary lesion site, but the specificity is lower for [sup.99m]Tc depreotide compared with FDG PET. Further, we confirm the finding of Lowe and coworkers (11) that there is no diagnostic advantage to using SUVs over visual inspection when assessing the primary lung lesion. The negative predictive values of the tests are reasonably high given the high prevalence of patients with cancer (78%) referred from our thoracic surgery clinics. Had the prevalence of disease been lower (eg, 45%) as might be the case if patients were referred from our pulmonary medicine clinics, the negative predictive values increase to 96% for FDG PET and 91% for [sup.99m]Tc depreotide. Thus, when considering our reported predictive values, it is important to be aware that values will vary in other centers depending on the prevalence of cancer in the referral population. If both examinations are performed and results are required to be negative to interpret a lesion as benign, despite the high prevalence of cancer in our series, only two malignant primaries in 122 of our patients (1.6%) with lung cancer would have been missed. This indicates that if the FDG PET and [sup.99m]Tc depreotide imaging findings in the region of the primary are negative, the patient is very unlikely to have lung cancer. As has been reported in other trials, (11,23) inflammatory diseases (particularly granulomatous disease) or misinterpreted areas of normal radiotracer accumulation were responsible for the false-positive findings in our series of patients. Our results with FDG PET are similar to the results of several studies (12,24) that have demonstrated high sensitivity with more modest specificity in the primary lesion. Though few published data are avail[sup.99m]Tc able regarding [sup.99m]Tc depreotide scanning, the sensitivity determined from our trial is similar but the specificity is lower than reported in other trials. Blum and coworkers reported a sensitivity and specificity of 93% and 88%, respectively, for the diagnosis of malignancy (25) and later reported values of 97% and specificity 73% from a larger multicenter trial. (18)
Our findings suggest that FDG PET may be marginally more accurate than [sup.99m]Tc depreotide in the hilar and mediastinal regions, though the difference between them was not statistically different. Several investigators have reported that FDG PET is a relatively accurate method for assessing the status of the mediastinal lymph node regions. A large meta-analysis (26) reported that the average sensitivity and specificity for malignancy were approximately 80% and 90%, respectively. The sensitivity is similar but the specificity is lower in our series compared with the meta-analysis, though similar to the specificity values reported by other groups of investigators. (27-29) We suspect that the somewhat reduced specificity seen in our group of patients is related to conditions such as bacterial pulmonary infection, granulomatous disease, and other active inflammatory conditions of the chest that are important known causes of false-positive scan findings. To our knowledge, this is the first reported study that examines lymph node staging in a large series of patients undergoing [sup.99m]Tc depreotide scintigraphy. In this direct comparison between FDG PET and [sup.99m]Tc depreotide, we found that these tests performed similarly in the hilum and mediastinum.
A combined PET-CT unit was not available for use in this trial. Likewise, a combined SPECT-CT unit was not available to scan patients after receiving [sup.99m]Tc depreotide. It is certainly possible that tumor staging would have been improved had PET-CT (or SPECT-CT) been utilized, particularly with regard to questions of chest wall invasion by the primary, properly interpreting midline nodal findings as N2 vs N3, and the potential to reduce false-positive distant findings by more precise localization. Preliminary evidence in a very small study (30) suggests that the accuracy of PET-CT in this patient group is superior to that of FDG-PET alone. If this finding is confirmed, undoubtedly FDG PET-CT will become an even more important tool for staging patients, especially in the assessment of distant metastatic disease.
However, until the results from future trials with adequate subject numbers are available, it is unclear if these newer and more expensive technologies will offer a significant advantage to patients with newly diagnosed non-small cell lung cancer.
However, because node stage alone does not alone determine appropriateness of definitive surgery, we have presented data based on overall or final stage. Our data indicate that neither FDG PET nor [sup.99m]Tc depreotide, when interpreted in combination with the chest CT scan, can be reliably used alone to accurately stage patients with non-small cell lung cancer. Only approximately one half of the patients with suspected lung cancer were correctly staged using either of the nuclear medicine examinations. Since there was no predictable pattern of false-negative or false-positive scan findings for either scan when evaluating sites distant from the primary lesion, we are unable to recommend that both examinations be performed in order to enhance staging accuracy. Of major importance, neither test appears to reliably separate surgical candidates from nonsurgical (stage IIIB and IV) candidates.
FDG PET reportedly will detect unsuspected distant metastatic disease in approximately 10 to 15% of patients. (23,31-32) While greatly impacting patient management, the likelihood of detecting unsuspected disease in our series is approximately the same with either examination (5%). Unexpected scan findings distant from the primary tumor should generally lead to further diagnostic investigation. Given the false-positive rate of unsuspected findings in 6% of our subjects, we believe that special care must be taken to confirm the findings of either examination with other imaging modalities or biopsy.
CONCLUSION
Our findings demonstrate that FDG PET and [sup.99m]Tc depreotide have equally high sensitivities for the detection of lung cancer in the primary lesion. Therefore, since the likelihood of non-small cell lung cancer is low (particularly when the prevalence of cancer in the population is not > 50%) when either test result is negative, test selection should be based on other variables such as availability and convenience ([sup.99m]Tc depreotide, unlike FDG PET, uses standard nuclear medicine gamma cameras and an easily compounded radiopharmaceutical), and cost. The two imaging examinations are comparable but distinctly less accurate when evaluating for evidence of metastatic spread of cancer. For this reason FDG PET or [sup.99m]Tc depreotide must be used with caution for this purpose.
Table 1–Sensitivity, Specificity, and Negative and Positive
Predictive Values for FDG PET and [sup.99m]Tc Depreotide Compared
With the Final Stage *
FDG PET
Positive Negative
Predictive Predictive
Lesion Location Sensitivity Specificity Value Value
Primary 96 (90-98) 71 (54-85) 92 (86-96) 83 (65-94)
Hilar/mediastinal 81 (62-92) 77 (68-85) 53 (38-68) 93 (84-97)
lymph nodes
[sup.99m]Tc Depreotide
Positive Negative
Predictive Predictive
Lesion Location Sensitivity Specificity Value Valne
Primary 94 (88-98) 51 (34-68) 87 (80-92) 72 (50-87)
Hilar/mediastinal 68 (48-83) 70 (60-79) 42 (29-57) 87 (77-93)
lymph nodes
* Data are presented as % (95% CI).
Table 2–Comparison of FDG PET Stage With Final Stage in 139 Subjects
Final Stage, No.
FDG PET
Stage No Cancer Stage I Stage II Stage IIIA
No cancer 24 5 0 0
Stage I 5 30 6 3
Stage II 2 3 3 1
Stage IIIA 2 6 0 4
Stage IIIB 1 4 3 2
Stage IV 0 2 2 4
Final Stage, No.
FDG PET
Stage Stage IIIB Stage IV
No cancer 1 0
Stage I 1 2
Stage II 3 0
Stage IIIA 2 1
Stage IIIB 7 1
Stage IV 1 8
Table 3–Comparison of [sup.99m]Tc Depreotide Stage With
Final Stage in 139 Subjects
Final Stage
[99m.sup]TcDepreotide No Stage Stage Stage Stage Stage
Stage Cancer I II IIIA IIIB IV
No cancer 17 4 0 1 2 0
Stage I 10 26 5 4 1 4
Stage II 2 8 3 3 2 0
Stage IIIA 3 3 1 6 3 1
Stage IIIB 2 5 3 0 6 2
Stage IV 0 4 2 0 1 5
Table 4–[sup.99m]Tc Depreotide Results in Misstaged FDG
PET Cases
FDG PET
[sup.99m]Tc Understaged Overstaged
Depreotide (n = 26) (n = 37)
Correctly staged 5 13
Understaged 1 2
Overstaged 20 22
Table 5–FDG Results in Misstaged
[sup.99m]Tc Depreotide Causes[sup.99m]Tc Depreotide
Understaged Overstaged
FDG PET (n = 32) (n = 44)
Correctly staged 11 22
Understaged 19 0
Overstaged 2 22
ACKNOWLEDGMENT: The authors thank Mitchell Thomas, CNMT; Jenifer Swearingen, RN; Amy Nibaur, RN; Dennis Sass, RN; Craig Larson, PA-C; John Richmond, CNMT; and Nicholas Rossi, MD, for assisting with this project.
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* From the Nuclear Medicine Section (Drs. Kahn and Bushnell, and Ms. Miller), Iowa City VA Medical Center; and Departments of Radiology (Drs. Berbaum and Menda) and Surgery (Dr. Kernstine and Ms. McLaughlin), University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA.
This work was performed at the Iowa city VA Medical Center and the University of Iowa, Roy J. and Lucille A. Carver College of Medicine.
Research support was provided in part by Berlex Laboratories, Inc. Manuscript received May 27, 2003; revision accepted September 5, 2003.
Correspondence to: Daniel Kahn, MD, Nuclear Medicine Section, 11.5, Iowa City VAMC, Iowa City, IA 52246; e-mail: danielkahn@uiowa.edu
COPYRIGHT 2004 American College of Chest Physicians
COPYRIGHT 2004 Gale Group
