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(Chest. 2004;126:1337-1343.)
© 2004 American College of Chest Physicians

Depreotide Scanning in Sarcoidosis*

A Pilot Study

Andrew F. Shorr, MD, MPH, FCCP; Donald L. Helman, MD; Christopher J. Lettieri, MD; Jamie L. Montilla, MD and Robert S. Bridwell, MD

* From the Pulmonary and Critical Care Medicine Service (Drs. Shorr, Helman, and Lettieri), Department of Medicine, and the Nuclear Medicine Service (Drs. Montilla and Bridwell), Department of Radiology, Walter Reed Army Medical Center, Washington, DC.

Correspondence to: Andrew F. Shorr, MD, MPH, FCCP, Pulmonary and Critical Care Medicine Service, Walter Reed Army Medical Center, 6900 Georgia Ave, NW, Washington, DC 20307; e-mail: afshorr{at}dnamail.com


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To determine whether sarcoidosis results in uptake on 99mTc-labeled depreotide (DP) scintigraphy and to generate preliminary data to guide the development of future trials exploring this imaging modality in sarcoidosis patients.

Design: Prospective cohort trial among a convenience sample of patients with sarcoidosis.

Setting: Tertiary care medical center pulmonary clinic.

Patients: Subjects in whom sarcoidosis has been diagnosed based on a biopsy revealing nonnecrotizing granulomas.

Interventions: Two hours after IV administration of 99mTc-DP, all patients underwent whole-body anterior and posterior planar imaging, followed by thoracic single-photon emission CT scanning. Images were interpreted by two nuclear medicine physicians who were blinded to the patient’s clinical status.

Measurements and results: The study cohort included 22 subjects (mean [± SD] age, 41.3 ± 9.3 years; 40% female). Approximately half of the cohort had stage I disease determined by chest radiographs (CXRs). The results of 99mTc-DP scintigraphy were positive for sarcoidosis in 18 individuals (81.8%; 95% confidence interval, 59.7 to 94.8%). Of the four persons lacking 99mTc-DP uptake, all had normalized their CXRs since the time of presentation. In the entire sample, the intraclass correlation between radiographic stage determined by CXR vs that determined by 99mTc-DP scintigraphy was robust ({kappa} = 0.79; p = 0.0005). Among patients with positive 99mTc-DP scan findings, the correlation was stronger ({kappa} = 0.94; p < 0.0001). Flow rates and lung volumes were lower in patients with parenchymal activity on 99mTc-DP scintigraphy (mean FEV1, 68.6 ± 13.9% predicted vs 84.5 ± 10.7% predicted, respectively [p = 0.012]; mean FVC, 74.0 ± 16.0% predicted vs 88.4 ± 12.7% predicted [p = 0.041]). 99mTc-DP scintigraphy correctly identified all sites of known nonpulmonary visceral involvement with sarcoidosis.

Conclusions: The results of 99mTc-DP imaging are often positive in sarcoidosis patients, and correlate with disease stage determined by CXR and pulmonary function. 99mTc-DP scintigraphy does not preclude the need for biopsy if this is indicated to confirm the diagnosis of sarcoidosis or to exclude the possibility of malignancy. 99mTc-DP scintigraphy merits further study in the evaluation and management of sarcoidosis.

Key Words: depreotide • gallium • nuclear imaging • sarcoidosis • somatostatin • stage


   Introduction
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 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The substance 99mTc-labeled depreotide (DP) is a novel radiopharmaceutical that binds to somatostatin receptors.1 Somatostatin-based nuclear scintigraphy was initially utilized in the evaluation of neuroendocrine tumors. Somatostatin receptors, however, also are overexpressed in other malignant and inflammatory conditions. With nuclear imaging techniques, 99mTc-DP represents a tool for evaluating pulmonary nodules in order to gauge the probability that the lesion is malignant. Currently, 99mTc-DP scanning is formally approved for use in this setting and is reported to have a sensitivity of 95% and a specificity of 85%.23

Causes for false-positive 99mTc-DP include hamartomas, acute infection, and granulomatous diseases.234 Sarcoidosis, a disease characterized by the presence of non-necrotizing granulomas, has anecdotally been reported to result in positive 99mTc-DP scan findings.5 In fact, somatostatin receptors have been found on the epithelioid cells and giant cells that comprise the sarcoid granuloma.6 Few prior studies have evaluated somatostatin receptor scintigraphy in sarcoidosis. Lebtahi and colleagues7 performed 111In-penetreotide (P) scans in 18 subjects with sarcoidosis. They noted that the findings of these scans were often positive and that areas of activity identified on nuclear imaging correlated with those found on chest radiographs (CXRs). 111In-P, though, failed to identify 40% of the sites of extrapulmonary sarcoidosis.7

Traditionally, 67Ga has been utilized in scanning for the detection of sarcoidosis. However, 67Ga-based imaging modalities have significant limitations. First, patients must be injected with the radiolabeled material at least 48 to 72 h before image acquisition. Second, there is significant interobserver variability in the interpretation of 67Ga scans.89 Third, although certain patterns noted on 67Ga scans are considered to be unique to sarcoidosis (eg, the lambda-panda pattern), the overall sensitivity and specificity of 67Ga varies significantly.101112 Some researchers have reported that this tool is highly accurate, while others have failed to observe similar findings.101112 Thus, at present 67Ga scanning is generally considered to have a limited role in the evaluation and management of sarcoidosis.48

We hypothesized that, because of the presence of somatostatin receptors on sarcoid granulomas, 99mTc-DP findings would frequently be positive in patients with sarcoidosis. We also speculated that 99mTc-DP would identify sites of extrapulmonary sarcoidosis. Moreover, there are no systematic data to help determine whether management trials utilizing 99mTc-DP should be performed in sarcoidosis patients. Therefore, we conducted a prospective prevalence trial of 99mTc-DP scanning in sarcoidosis.


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Subjects
The study population comprised a convenience sample of patients with sarcoidosis who were seen at our institution between January and June 2002. The original diagnosis of sarcoidosis was based on the histologic demonstration of non-necrotizing granulomas with special stains that failed to reveal either fungal or mycobacterial organisms. Patients in whom sarcoidosis was diagnosed, based only on their clinical presentation (ie, without biopsy evidence of non-necrotizing granulomas), and those who were < 18 years of age were not eligible for this study. The prior or current use of corticosteroids (or other therapies for sarcoidosis) did not preclude enrollment. In order to limit potential confounding from other conditions, patients were excluded if they had been diagnosed with pneumonia in the preceding 3 months or if they had or were being evaluated for any malignant condition. All patients approached to join in this study agreed to participate, and subjects provided written, informed consent. This investigation was approved by our hospital’s institutional review board.

Evaluation
All subjects underwent a standard evaluation, which included a history and physical examination, a CXR, and pulmonary function tests (PFTs) with the measurement of the single-breath diffusing capacity of the lung for carbon monoxide (DLCO). Radiographic stage was defined by the CXR performed when the patient initially had received a diagnosis of sarcoidosis and followed the approach of Scadding,13 as follows: stage 0, normal CXR; stage I, bilateral hilar lymphadenopathy alone; stage II, bilateral hilar lymphadenopathy with interstitial infiltrates; and stage III, interstitial infiltrates alone. All patients also underwent a CXR prior to 99mTc-DP scanning. The PFT results and DLCO values were interpreted in accordance with the guidelines of the American Thoracic Society.14 Normal values were derived from Crapo et al,15 and corrections for race were made. The DLCO was further corrected for hemoglobin. Values for PFTs and DLCO were considered to be abnormal if they fell outside the 95% confidence interval (CI) for the predicted values. We measured the erythrocyte sedimentation rate and the angiotensin-converting enzyme (ACE) level.16 We recorded current and prior therapy for sarcoidosis and the presence of extrapulmonary sarcoidosis. Extrapulmonary sarcoidosis was defined based on the classifications used by A Case Control Epidemiology Study of Sarcoidosis study group.17

99mTc-DP Scanning
For 99mTc-DP scintigraphy, we utilized a commercially available radiolabeled pharmaceutical (NeoTect; Berlex; Raritan, NJ). This comes in kit form with vials of 50 µg DP peptide. The DP is reconstituted with approximately 50 mCi 99mTc pertechnetate. Within 3 h of kit preparation, the 99mTc-DP was injected IV into each patient. Approximately 1 h after injection, image acquisition was begun. Anterior and posterior planar whole-body images were obtained with a scan speed of 15 cm/min in a matrix of 128 x 128. Immediately after whole-body planar imaging, thoracic single-photon emission CT imaging was performed. Single-photon emission CT imaging employed a 64 x 64 matrix.

End Points
The primary study end point was the occurrence of a positive finding of the 99mTc-DP scan. Two nuclear medicine physicians interpreted all 99mTc-DP scans. These observers were blinded to the patient’s clinical status and the results of other testing. Disagreements as to interpretation were resolved through consensus. The relationship between the stage determined by CXR and the stage determined by 99mTc-DP scanning represented a secondary end point. Hence, the interpreters categorized the findings of the 99mTc-DP images as negative, positive in the hila alone, positive in the hila and the parenchyma, or positive only in the lung parenchyma, corresponding to the CXR staging system developed by Scadding.13 In instances in which the CXR had changed (eg, the disease had resolved) in the interval between diagnosis and the time when nuclear imaging was performed, we compared both CXRs to the 99m Tc-DP scan. We also compared the 99mTc-DP interpretations with the results of PFTs. The activity in extrapulmonary locations seen on 99mTc-DP scans was recorded in order to identify sites of nonpulmonary sarcoidosis.

Statistical Analysis
We compared the correlation between stage as determined by CXR and that determined by 99mTc-DP scanning with the {kappa} statistic. A {kappa} statistic of > 0.8 is considered to represent strong agreement. Continuous data are reported as the mean ± SD. We utilized the Student t test to analyze continuous variables. The {chi}2 test was employed to compare categoric variables except in cases in which the expected values were small. In these instances, we relied on the Fisher exact test. All tests were two-tailed, and a p value of < 0.05 was assumed to represent statistical significance. Ninety-five percent CIs are reported where appropriate. Analyses were done using a statistical software package (SPSS, version 10.0; SPSS; Chicago, IL).

To determine our sample size for this pilot study, we assumed that the findings of 99mTc-DP scans would be positive in 70% of patients. Setting the CI around that estimate of the prevalence to be ± 20%, we calculated that we would require 20 subjects.


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The study cohort included 22 subjects. As shown in Table 1 , the mean age was 41.3 ± 9.3 years, and approximately 40% of the patients were female. The population was evenly divided between African Americans and whites. The mean duration of sarcoidosis prior to enrollment was 4.2 ± 3.1 years. Six subjects were receiving treatment for sarcoidosis when the 99mTc-DP scans were obtained. The therapeutic agents utilized included corticosteroids (three patients), methotrexate (two patients), and infliximab (three patients), with several individuals having been treated with combination regimens. Radiographically, the most common CXR stage was stage I and was seen in 54.5% of cases.


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  		Table 1.. Subject Characteristics (n = 22)*

 
99mTc-DP scans showed uptake in the chest in 81.8% of patients (95% CI, 59.7 to 94.8%). Among the four patients without evidence of activity on 99mTc-DP images, the CXR findings of all had normalized since they had received the initial diagnosis of sarcoidosis. In other words, all patients with abnormal CXRs had evidence of uptake by 99mTc-DP scanning. Patterns of 99mTc-DP activity noted on 99mTc-DP images generally conformed to the accepted staging system for sarcoidosis (Fig 1, 2 ). We failed to note patterns of DP uptake that mimicked either the lambda or panda patterns described with 67Ga scintigraphy.



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  		Figure 1.. Coronal images of the chest demonstrate intense, focal, bilateral hilar 99mTc-DP uptake.

 


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  		Figure 2.. Axial and coronal images of the chest demonstrate bilateral, diffuse, increased parenchymal lung uptake.

 
There was a strong correlation between the stage determined by CXR and that determined by 99mTc-DP scan. Based on the stage determined by the CXR obtained when the subject initially received a diagnosis, the interstudy agreement was high ({kappa} = 0.79; p = 0.0005). There was perfect concordance in 17 subjects (77.3%) as to the stage determined by both CXR and 99mTc-DP scan. When restricted to patients who had abnormal CXR findings at the time of 99mTc-DP image acquisition, the interstudy agreement was stronger ({kappa} = 0.94; p = 0.0001). In this instance, 99mTc-DP scanning "mis-staged" only one subject and revealed activity in the lung parenchyma when the lung fields were seen as being clear on the CXR. Comparing the CXRs that had been performed contemporaneously with the nuclear scans (as opposed to ones performed at the time of the initial diagnosis) to the 99mTc-DP scan results revealed an overall agreement in 95.5% of subjects.

As shown in Table 2 , evidence of parenchymal activity on 99mTc-DP scans (11 patients) was associated with worse pulmonary function. Patients with positive parenchymal 99mTc-DP scan findings had a mean FVC of 68.6 ± 13.9% compared to 84.5 ± 10.7% in patients who lacking parenchymal activity (p = 0.012). Those with parenchymal uptake were 20.3 times (95% CI, 2.3 to 176.8) more likely to have an abnormal FVC (eg, below the predicted 95% CI). Similar results were seen in terms of the FEV1 with a mean FEV1 of 74.0 ± 16.0% in persons with positive parenchymal scans as opposed to 88.4 ± 12.7% among those with no 99mTc-DP activity in the lung tissue. Neither the DLCO nor the DLCO corrected for alveolar volume differed based on the status of the parenchyma as determined by 99mTc-DP imaging. However, measured as a categoric variable, all persons with evidence of 99mTc-DP activity in the parenchyma had abnormally low DLCO values compared to only 54.5% of individuals with normal parenchyma seen on 99mTc-DP scintigraphy (p = 0.035). The serum markers of inflammation were normal in nearly all patients and also did not differ based on the findings of 99mTc-DP scintigraphy. Specifically, the ACE level was elevated in seven subjects. The mean ACE level was 45.9 ± 27.0 U/L in those without activity on 99mTc-DP scans, while it was 41.0 ± 34.7 U/L in those with normal scintigraphy findings (difference was not significant).


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  		Table 2.. PFTs and Parenchymal Activity*

 
Four subjects had known extrapulmonary sarcoidosis (cardiac, two subjects; neurologic, one subject; skin, one subject). An example of cardiac involvement is shown in Figure 3 . In the three noncutaneous cases, 99mTc-DP scanning revealed intense uptake in the involved organs. There was no evidence of extrapulmonary activity in the remaining patients, all of whom lacked clinical evidence of extrapulmonary sarcoidosis.



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  		Figure 3.. Top: axial images of the chest demonstrate diffuse, left ventricular increased 99mTc-DP uptake (arrow). Bottom: coronal images of the chest demonstrate diffuse left ventricular increased 99mTc-DP uptake (arrowheads).

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This prospective pilot study demonstrates that 99mTc-DP scans are frequently positive in patients with sarcoidosis. Sites of 99mTc-DP uptake correlate closely with the results of both CXRs and PFTs. 99mTc-DP scans also appear to identify sites of extrapulmonary involvement in patients with sarcoidosis.

Traditionally, among nuclear medicine modalities, 67Ga-based imaging has been utilized in sarcoidosis. However, the role for 67Ga scanning remains controversial. For example, in a multicenter study18 of 67Ga scintigraphy involving > 600 subjects, nearly one in four patients with evident involvement seen by CXR had no 67Ga uptake in the thorax. Similarly, although some investigators have reported a correlation between activity seen on 67Ga imaging in the parenchyma and evidence of alveolitis determined by BAL, others have not been able to corroborate these observations.1920 For the diagnosis of sarcoidosis, 67Ga has a sensitivity that ranges from 60 to 90%.8101112 On the other hand, 67Ga has a poor specificity. The lambda-panda pattern, considered by some to be classic for sarcoidosis, also may be seen in patients infected with HIV, rheumatoid arthritis, and Sjogren syndrome.8 In a study to assess the role for 67Ga in predicting prognosis, moreover, Mana et al21 reported that 67Ga imaging did not add to other readily available tools such as the CXR and serial PFTs. Because of these limitations, the role for 67Ga is limited. Currently, some authors recommend 67Ga scanning (1) as an alternative to biopsy in patients with CXRs exhibiting classic stage I disease, (2) as a diagnostic aid in patients who present with signs and symptoms of sarcoidosis but normal CXR findings (ie, stage 0 disease), and (3) as a means for identifying alternative sites to biopsy.58

Somatostatin analogs represent a novel alternative to 67Ga. In an early report22 focusing on 111In-P, this technique detected new sites of granulomatous activity in 9 of 13 patients. In a larger series of 46 individuals with sarcoidosis, Kwekkeboom and colleagues23 noted that 111In-P detected known adenopathy and parenchymal involvement in 97% of cases. 111In-P identified new sites of sarcoidosis activity in 50% of subjects. On repeat scanning, 111In-P activity diminished in each of these trials among the patients treated with corticosteroids. 111In-P imaging also appears to be more accurate than 67Ga imaging.2223 Lebtahi et al7 compared 67Ga imaging to 111In-P imaging in 18 persons with sarcoidosis. Although 67Ga imaging localized to two thirds of the clinically involved sites, 111In-P imaging detected 83% of areas of clinical sarcoid activity. One concern with 111In-P imaging is its limited ability to locate extrapulmonary sarcoidosis. For example, in the trial conducted by Lebtahi et al,7 111In-P imaging failed to reveal several known cases of neurosarcoidosis and, overall, missed approximately 40% of all extrathoracic lesions. Technical factors also limit the utility of 111In-P scintigraphy in that patients must return for repeat image acquisition 24 h after initial injection.

No other systematic trial has examined 99mTc-DP imaging in sarcoidosis. Anecdotal reports45 initially indicated that 99mTc-DP imaging might lead to false-positive results in the evaluation of suspected pulmonary malignancies. Our preliminary observations underscore the potential role that 99mTc-DP imaging may have in sarcoidosis. 99mTc-DP imaging correlated well with CXR findings, which are perhaps the strongest predictor of outcome in sarcoidosis patients. 99mTc-DP imaging, unlike the performance of 67Ga in other studies, correctly staged almost all subjects with sarcoidosis. Furthermore, the relationship between lung tissue uptake and the results of certain PFTs suggests that 99mTc-DP imaging may detect the extent of lung injury arising from sarcoidosis.

For extrapulmonary sarcoidosis, 99mTc-DP imaging might prove most useful. There are no standard, accepted approaches to the evaluation of suspected extrapulmonary sarcoidosis. 201Tl scintigraphy, for example, which has been studied in cardiac sarcoidosis patients, frequently demonstrates heterogeneous cardiac uptake in patients without clinical disease.48 More specifically, Kinney et al24 noted abnormal 201Tl cardiac scans in 30% of subjects with sarcoidosis but no suspected cardiac involvement. Similarly, other investigators have reported2526 that positive 201Tl scintigraphy findings had no prognostic significance because the test was overly sensitive. In our study, although it was very small, 99mTc-DP imaging nonetheless correctly identified all sites of major, clinically significant visceral involvement in sarcoidosis patients.

Beyond 99mTc-DP and 67Ga imaging, positron emission tomography (PET) scanning is undergoing evaluation for its use in detecting sarcoidosis. No published trials have systematically investigated the role for PET scanning in assessing the extent of either lymph node or parenchymal involvement in sarcoidosis. Rather, anecdotal reports2728 have described that PET imaging findings may be positive in the mediastinum of patients with sarcoidosis. Several retrospective series29 also have suggested that PET scanning has a role in the diagnosis of extrapulmonary sarcoidosis. Yamagishi et al29 studied 17 patients with cardiac sarcoidosis, and PET imaging findings were positive in > 80% of these individuals. More importantly, among their seven subjects treated with corticosteroids for cardiac involvement, all showed improvement on the cardiac PET scans, suggesting that PET imaging may facilitate management of this condition.

Readers should note that we are not suggesting that 99mTc-DP scintigraphy should be performed in patients with sarcoidosis. This imaging modality may add nothing to the present approach to sarcoidosis. Rather, our purpose was to demonstrate that additional trials are warranted. Beyond sarcoidosis, our findings have implications for the role for 99mTc-DP imaging in the management of suspected pulmonary malignancies. In appropriate clinical settings, nuclear radiologists and pulmonologists should consider that activity seen on 99mTc-DP imaging may represent sarcoidosis rather than cancer. Conversely, in patients with known sarcoidosis who are undergoing evaluation for a potential malignancy, 99mTc-DP imaging does not allow one to conclusively differentiate a superimposed malignant process from the underlying disease state. As such, 99mTc-DP imaging should not be considered an acceptable diagnostic alternative to biopsy.

Our study has several limitations. First, although prospective, this trial was cross-sectional in design. We lack information about changes in the results of 99mTc-DP scintigraphy over time. Since sarcoidosis has a variable natural history, such data are crucial before concluding that 99mTc-DP imaging adds to our current approach to the detection of sarcoidosis. Second, our sample size was small. This necessarily limits our ability to draw conclusions. However, this trial was conducted as a pilot study in order to provide preliminary results so as to determine whether further work in this area is warranted. Third, only one center participated in this investigation. As such, our findings have limited generalizability.

In summary, sarcoidosis often yields positive findings on 99mTc-DP scans. Because of the nexus among the findings of CXRs, PFTs, and 99mTc-DP scintigraphy, future prospective trials are warranted to exploring an expanded role for 99mTc-DP imaging in the evaluation and management of sarcoidosis. In instances in which malignancy is a concern, 99mTc-DP imaging should not be considered an acceptable surrogate for biopsy.


   Footnotes
 
Abbreviations: ACE = angiotensin-converting enzyme; CI = confidence interval; CXR = chest radiograph; DLCO = diffusing capacity of the lung for carbon monoxide; DP = depreotide; P = penetreotide; PET = positron emission tomography; PFT = pulmonary function test

The opinions expressed herein are not to be construed as official or as reflecting the policy of either the Department of Defense or the Department of the Army.

Received for publication January 27, 2004. Accepted for publication April 22, 2004.


   References
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 Abstract
 Introduction
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 Results
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 References
 

  1. Vallabhajosula, S, Moyer, BR, Lister-James, J, et al (1996) Preclinical evaluation of technetium-99m-labeled somatostatin receptor-binding peptides. J Nucl Med 37,1016-1022[Abstract/Free Full Text]
  2. Blum, J, Handmaker, H, Lister-James, J, et al A multicenter trial with a somatostatin analog (99m)Tc depreotide in the evaluation of solitary pulmonary nodules. Chest 2000;117,1232-1238[Abstract/Free Full Text]
  3. Blum, JE, Handmaker, H, Rinne, NA The utility of a somatostatin-type receptor binding peptide radiopharmaceutical (P829) in the evaluation of solitary pulmonary nodules. Chest 1999;115,224-232[Abstract/Free Full Text]
  4. Schuster, DM, Alazraki, N Gallium and other agents in diseases of the lung. Semin Nucl Med 2002;32,193-211[CrossRef][ISI][Medline]
  5. Kwekkeboom, DJ, Krenning, EP Somatostatin receptor imaging. Semin Nucl Med 2002;32,84-91[CrossRef][ISI][Medline]
  6. ten Bokum, AM, Hofland, LJ, de Jong, G, et al Immunohistochemical localization of somatostatin receptor sst2A in sarcoid granulomas. Eur J Clin Invest 1999;29,630-636[CrossRef][ISI][Medline]
  7. Lebtahi, R, Crestani, B, Belmatoug, N, et al Somatostatin receptor scintigraphy and gallium scintigraphy in patients with sarcoidosis. J Nucl Med 2001;42,21-26[Abstract/Free Full Text]
  8. Mana, J Nuclear imaging: 67Gallium, 201thallium, 18F-labeled fluoro-2-deoxy-D-glucose positron emission tomography. Clin Chest Med 1997;18,799-811[CrossRef][ISI][Medline]
  9. Abe, S, Munakata, M, Nishimura, M, et al Gallium-67 scintigraphy, bronchoalveolar lavage, and pathologic changes in patients with pulmonary sarcoidosis. Chest 1984;85,650-655[Abstract/Free Full Text]
  10. Beaumont, D, Herry, JY, Sapene, M, et al Gallium-67 in the evaluation of sarcoidosis: correlations with serum angiotensin-converting enzyme and bronchoalveolar lavage. Thorax 1982;37,11-18[Abstract]
  11. Nosal, A, Schleissner, LA, Mishkin, FS, et al Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis. Ann Intern Med 1979;90,328-331[ISI][Medline]
  12. Klech, H, Kohn, H, Kummer, F, et al Assessment of activity in sarcoidosis: sensitivity and specificity of 67Gallium scintigraphy, serum ACE levels, chest roentgenography, and blood lymphocyte subpopulations. Chest 1982;82,732-738[Abstract/Free Full Text]
  13. Scadding, JG Prognosis of intrathoracic sarcoidosis in England: a review of 136 cases after five years’ observation. BMJ 1961;5261,1165-1172[ISI][Medline]
  14. American Thoracic Society. Standardization of spirometry: 1994 update. Am J Respir Crit Care Med 1995;152,1107-1136[ISI][Medline]
  15. Crapo, RO, Morris, AH, Gardner, RM Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981;123,659-664[ISI][Medline]
  16. Lieberman, J Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med 1975;59,365-372[CrossRef][ISI][Medline]
  17. Judson, MA, Baughman, RP, Teirstein, AS, et al Defining organ involvement in sarcoidosis: the ACCESS proposed instrument; ACCESS Research Group—a case control etiologic study of sarcoidosis sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 1999;16,75-86[ISI][Medline]
  18. Rizzato, G, Blasi, A A European survey on the usefulness of 67Ga lung scans in assessing sarcoidosis: experience in 14 research centers in seven different countries. Ann N Y Acad Sci 1986;465,463-478[Abstract]
  19. Line, BR, Hunninghake, GW, Keogh, BA, et al Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage. Am Rev Respir Dis 1981;123,440-446[ISI][Medline]
  20. Bisson, G, Drapeau, G, Lamoureux, G, et al Computer-based quantitative analysis of gallium-67 uptake in normal and diseased lungs. Chest 1983;84,513-517[Abstract/Free Full Text]
  21. Mana, J, Salazar, A, Pujol, R, et al Are the pulmonary function tests and the markers of activity helpful to establish the prognosis of sarcoidosis? Respiration 1996;63,298-303[ISI][Medline]
  22. Vanhagen, PM, Krenning, EP, Reubi, JC, et al Somatostatin analogue scintigraphy in granulomatous diseases. Eur J Nucl Med 1994;21,497-502[ISI][Medline]
  23. Kwekkeboom, DJ, Krenning, EP, Kho, GS, et al Somatostatin receptor imaging in patients with sarcoidosis. Eur J Nucl Med 1998;25,1284-1292[CrossRef][ISI][Medline]
  24. Kinney, EL, Jackson, GL, Reeves, WC, et al Thallium-scan myocardial defects and echocardiographic abnormalities in patients with sarcoidosis without clinical cardiac dysfunction: an analysis of 44 patients. Am J Med 1980;68,497-503[CrossRef][ISI][Medline]
  25. Haywood, LJ, Sharma, OP, Siegel, ME, et al Detection of myocardial sarcoidosis by thallium 201 imaging. J Natl Med Assoc 1982;74,959-964[Medline]
  26. Sharma, OP, Siegel, M, Haywood, LJ Role of thallium 201 scanning in the management of myocardial sarcoidosis. Arch Monaldi 1981;36,79-86[Medline]
  27. Alavi, A, Gupta, N, Alberini, JL, et al Positron emission tomography imaging in nonmalignant thoracic disorders. Semin Nucl Med 2002;32,293-321[CrossRef][ISI][Medline]
  28. Pitman, AG, Hicks, RJ, Binns, DS, et al Performance of sodium iodide based (18)F-fluorodeoxyglucose positron emission tomography in the characterization of indeterminate pulmonary nodules or masses. Br J Radiol 2002;75,114-121[Abstract/Free Full Text]
  29. Yamagishi, H, Shirai, N, Takagi, M, et al Identification of cardiac sarcoidosis with (13)N-NH(3)/(18)F-FDG PET. J Nucl Med 2003;44,1030-1036[Abstract/Free Full Text]



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