HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Francis G. Duhaylongsod Val J. Lowe Walter G. Wolfe Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duhaylongsod, F. G. Articles by Wolfe, W. G. Search for Related Content PubMed PubMed Citation Articles by Duhaylongsod, F. G. Articles by Wolfe, W. G. Related Collections Related Article

Ann Thorac Surg 1995;60:1348-1352
© 1995 The Society of Thoracic Surgeons

---

Original Articles: General Thoracic

Lung Tumor Growth Correlates With Glucose Metabolism Measured by Fluoride-18 Fluorodeoxyglucose Positron Emission Tomography

Departments of Surgery and Radiology, Duke University Medical Center, Durham, North Carolina

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. The growth rate, or doubling time, of radiographically indeterminate pulmonary abnormalities is an important determinant of malignancy. Prospective calculation of doubling time, however, delays diagnosis and treatment. Positron emission tomography (PET) using the glucose analogue fluoride-18 fluorodeoxyglucose (FDG) measures the enhanced glucose uptake characteristic of neoplastic cells. We postulated that if FDG activity correlates with doubling time, then PET may allow prompt diagnosis of lung cancer.

Methods. From March 1992 to July 1993, all patients with indeterminate focal pulmonary abnormalities were eligible for FDG PET imaging. In 53 patients, serial chest radiographs or computed tomograms were available and doubling time was computed. The FDG activity within the lesion was expressed as a standardized uptake ratio.

Results. The mean standardized uptake ratio (± SD) was 5.9 ± 2.7 in 34 patients with cancer, versus 2.0 ± 1.7 in 19 with benign disease (p < 0.001). Using a criterion of standardized uptake ratio 2.5 or greater for malignancy, the accuracy of PET was 92% (49 of 53). The standardized uptake ratio was significantly correlated with doubling time (r = -0.89; p = 0.002).

Conclusion. These data suggest a direct relation between tumor growth and FDG uptake in lung cancer. The technique of FDG PET demonstrates exceptional accuracy and may permit prompt diagnosis of lung cancer.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
See also page 1352.

Focal pulmonary abnormalities frequently present a diagnostic challenge. The malignant potential of a radiographically indeterminate pulmonary abnormality is often suggested by rapid growth, or a brief doubling time. With conventional chest imaging techniques, however, the prospective calculation of doubling time potentially delays the diagnosis and treatment of patients with lung cancer. Furthermore, chest radiography and computed tomography have varying sensitivities, ranging from 52% to 80%, and lack sufficient specificity to provide a definitive diagnosis [1, 2]. Thus, invasive biopsy is often performed. Recently, growing interest has focused on imaging modalities that rely on metabolic rather than anatomic properties of lung cancer to guide medical therapy. One example is positron emission tomography (PET).

Positron emission tomography using the glucose analogue fluoride-18 fluorodeoxyglucose (FDG) detects the enhanced glucose metabolism characteristic of certain neoplastic cells. We postulated that if glucose metabolism measured by FDG uptake correlates with tumor growth rate assessed radiographically, then PET may allow prompt diagnosis of lung cancer.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Between March 1992 and July 1993, all patients referred to the Duke University Medical Center chest medicine and thoracic surgery clinics with focal pulmonary abnormalities indeterminate by chest radiography and computed tomography were eligible for enrollment into the study. Protocol design was approved by the institutional review board, and informed consent was obtained from all participants. General exclusion criteria included age less than 18 years, pregnancy, scheduling constraints because of immediacy of operation, and patient refusal.

The technical and procedural details of PET imaging in the chest have been reported [3]. In summary, patients fasted for 4 hours before study and were positioned in the PET unit so that the pulmonary abnormality was near the center of the longitudinal field of view. The PET unit (4096 Plus; General Electric Medical Systems, Milwaukee, WI) produced 15 axial images along a 97-mm longitudinal field with a spatial resolution of about 5 mm. Image processing and reconstruction were performed using a VAX 4000-300 computer system and a VAX 3100 work station (Digital Equipment, Marlboro, MA). After January 1993, a second PET unit was added (Advance; General Electric Medical Systems). This unit produced 35 axial images along a 150-mm longitudinal field; image processing and reconstruction were performed using a Hewlett Packard Apollo Series 765. Transmission scans were obtained using ⁶⁸Ge pin sources to correct for soft-tissue attenuation and to localize the radiographic abnormality. Emission scans were obtained over a 20-minute period starting 30 minutes after intravenous injection of 10 mCi (370 MBq) of FDG. In our later experience, emission scans were acquired starting 60 minutes after FDG injection on the basis of studies using dynamic PET imaging. These studies established the optimum scanning protocol for distinguishing benign from malignant pulmonary lesions [4]. Fluoride-18 fluorodeoxyglucose was synthesized in our laboratory using standard methods [5]. A region of interest was chosen on the emission images to include the area of highest FDG activity, corresponding to the radiographic abnormality. The mean activity in the region of interest (ROI) was corrected for radioactive decay, and a standardized uptake ratio (SUR) was calculated according to the formula:

To minimize observer bias, the region of interest was selected and SUR computed by a nuclear medicine physician (VJL) without prior knowledge of the patient's clinical history, physical examination, or laboratory data (including all cytology and biopsy reports).

For the calculation of doubling time, the following requirements were met: (1) Serial imaging studies were performed at the same facility using standard techniques; (2) all pulmonary lesions had distinct radiographic margins (infiltrates and ill-defined opacities were excluded); (3) patients treated with radiotherapy or chemotherapy during the interval between imaging studies were excluded; and (4) at least two chest radiographs or computed tomography scans were available, taken a minimum of 60 days apart. The maximum and perpendicular diameters of the lesion were measured, and the calculated average was defined as the tumor diameter (d). The doubling time (DT) was computed using the formula [6]:

where d₀ and d_t are the tumor diameter measurements (mm) separated by a time interval t (days).

Histopathologic diagnosis was obtained in all patients by transbronchial or transthoracic needle aspiration biopsy or open lung biopsy, with one exception. This patient was followed with regularly scheduled plain chest radiographs for more than 2 years, with gradual resolution of the abnormality.

Calculations of sensitivity, specificity, and accuracy were done using standard equations. Comparison of SUR values between groups with benign and malignant disease was performed using a two-sided, unpaired Student's t test. The null hypothesis was rejected at the = 0.05 significance level. The mean ± standard deviation are reported.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Between March 1992 and July 1993, 81 patients with focal indeterminate pulmonary abnormalities underwent FDG PET imaging. In 53 cases, serial chest radiographs, computed tomography scans, or both were available and doubling time was calculated retrospectively (Table 1). The mean age was 61 ± 4 years, and 33 patients were male (62%). The radiographic abnormalities included 39 solitary pulmonary nodules (defined as a focal abnormality 4 cm or less in diameter) and 14 pulmonary masses (greater than 4 cm in diameter). The anatomic sites of the radiographic lesions are listed in Table 1.

View larger version (18K): [in this window] [in a new window]   Fig 1. . Relation between fluoride-18 fluorodeoxyglucose uptake, expressed as standardized uptake ratio, and calculated doubling time. (Closed triangles = malignant lesions; open circles = benign lesions.)

View larger version (19K): [in this window] [in a new window]   Fig 2. . Relation between fluoride-18 fluorodeoxyglucose uptake, expressed as standardized uptake ratio (SUR), and lesion diameter. (Closed triangles = malignant lesions; open circles = benign lesions; open squares with error bars = group means ± standard deviations; dashed line = threshold criterion for malignancy.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
The natural history of the malignant pulmonary nodule is one of exponential growth. In early studies, the growth rates of malignant tumors were determined from serial chest radiographs and expressed quantitatively as doubling time, or the time required for the radiographic nodule to double in volume [7]. That most lung cancers demonstrate exponential growth was supported by the observation that doubling times remained constant in 80% to 90% of tumors found in published series [6]. In contrast, benign pulmonary lesions grow very slowly if at all, with doubling times that are significantly greater than those of malignant tumors [8, 9]. Indeed, the present study revealed a mean doubling time of 600 days for benign lesions versus 215 days for malignant lesions. In a recent review, Lillington [10] noted that most benign pulmonary abnormalities have doubling times greater than 450 days, whereas malignant lesions usually exhibit doubling times less than 400 days. The familiar dictum that absence of growth in a pulmonary nodule over a 2-year period suggests benignancy implies a doubling time of more than 700 days. Thus, benign and malignant focal pulmonary lesions can be differentiated on the basis of growth rates. Although some authors have recommended prospective calculation of doubling time through regularly scheduled chest radiographs for the management of selected patients with solitary pulmonary nodules [8, 11], the potential delay in the diagnosis and treatment of lung cancer as well as the relative efficacy and safety of current invasive diagnostic techniques compel most surgeons to reject this approach.

Malignant tumor cells often display enhanced glucose metabolism and uncontrolled growth. Since the original description by Warburg and colleagues in 1923 [12], others have verified the increase in activity of key glycolytic enzymes in cancer cells [13]. The concomitant rise in cellular glucose uptake can be measured using PET with the glucose analogue FDG. Fluoride-18 fluorodeoxyglucose enters the cell through facilitated transport, undergoes phosphorylation by hexokinase, and becomes trapped intracellularly. Because the metabolism of phosphorylated FDG is extremely slow, its rate of appearance within the cell correlates directly with glycolytic flux [13]. Thus, FDG PET measures the augmented glucose metabolism characteristic of malignant cells in vivo. In several experimental and clinical studies, significant increases in FDG uptake have been demonstrated in all types of lung cancer [14–16].

Glucose metabolism measured by FDG PET correlates with the doubling time of malignant pulmonary lesions. In this study, the cellular uptake of FDG and the calculated doubling time of indeterminate pulmonary lesions were inversely related. Thus, high levels of glucose metabolism were associated with shorter tumor doubling times, or faster rates of tumor growth. Other studies have confirmed the relation between glucose metabolism measured by FDG PET and the growth rate in different tumor types. In a study of 23 patients with primary cerebral tumors, DiChiro and co-workers [17] were the first to establish a link between the glycolytic activity measured by FDG PET and the rate of tumor growth in vivo. They postulated that a progressive increase in glucose metabolism accompanied the transformation from a slow to rapidly growing, poorly differentiated tumor [17]. In a study of 13 patients with malignant head and neck tumors, Minn and associates [18] examined the relation between glucose metabolism measured by FDG PET and tumor proliferative activity assessed by DNA flow cytometry. Their findings suggested that glucose metabolism correlated directly with the proportion of cells in the S phase of the cell cycle [18]. Similarly, Okada and colleagues [19] compared FDG uptake and cellular proliferative activity in 23 patients with malignant lymphoma of the head and neck. Using a monoclonal antibody directed against a nuclear antigen present only in proliferating cells (Ki-67), they demonstrated that Ki-67 immunoreactivity as well as the number of cellular mitoses observed under light microscopy increased in proportion to FDG uptake [19]. These data suggest that in certain tumor cell types, glucose metabolism measured by FDG PET varies proportionately with tumor growth.

Based on the preceding evidence that indeterminate focal pulmonary lesions can be differentiated by doubling time or growth rate and that doubling time is proportionate to glucose metabolism, it is reasonable to conclude that benign and malignant pulmonary lesions can be separated by quantitating glucose metabolism using FDG PET. Indeed, in this cohort of patients, the mean FDG activity in malignant lesions was significantly higher than in benign lesions. Using the previously derived criterion for malignancy of SUR 2.5 or greater, FDG PET demonstrated a sensitivity of 100%, a specificity of 79%, and an accuracy of 92%. These values are similar to those reported recently by Scott and colleagues [20] in a series of 47 patients who underwent diagnostic screening for lung cancer. Furthermore, FDG PET compares favorably with other more invasive diagnostic modalities currently in use, such as transthoracic needle aspiration biopsy [21, 22] and fiberoptic bronchoscopy [23, 24]. We suggest that by exhibiting superior sensitivity in the diagnosis of benign disease, combined with lower morbidity and less cost, FDG PET may be the preferred diagnostic modality in selected patients with focal pulmonary abnormalities.

In summary, indeterminate focal pulmonary lesions can be differentiated on the basis of doubling time. For malignant lesions, doubling time correlates with glucose metabolism measured by FDG PET. In our cohort of patients, we observed a direct relation between tumor growth rate assessed radiographically and FDG uptake in lung cancer. Thus, by quantitating glucose metabolism, FDG PET can differentiate benign from malignant pulmonary lesions with exceptional sensitivity and specificity.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Presented at the Forty-first Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 12–14, 1994.

Address reprint requests to Dr Wolfe, Duke University Medical Center, PO Box 3507, Durham, NC 27710.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

1. McLoud TC, Bourgouin PM, Greenberg RW, et al. Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. Radiology 1992;182:319–23.[Abstract/Free Full Text]
2. Webb WR, Gatsonis C, Zerhouni EA, et al. CT and MR imaging in staging non-small cell bronchogenic carcinoma: report of the Radiologic Diagnostic Oncology Group. Radiology 1991;178:705–13.[Abstract/Free Full Text]
3. Duhaylongsod FG, Lowe VJ, Patz EF Jr, Vaughn AL, Coleman RE, Wolfe WG. Detection of primary and recurrent lung cancer using F-18 fluorodeoxyglucose positron emission tomography (FDG PET). J Thorac Cardiovasc Surg (in press).
4. Lowe VJ, Delong JM, Hoffman EF, Patz EF, Coleman RE. Dynamic FDG-PET imaging of focal pulmonary abnormalities to identify optimum time for imaging. 41st Annual Meeting of the Society of Nuclear Medicine, Orlando, FL, 1994.
5. Hamcher K, Coenen HH, Stocklin G. Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 1986;27:235–8.[Abstract/Free Full Text]
6. Geddes DM. The natural history of lung cancer: a review based on rates of tumor growth. Br J Dis Chest 1979;73:1–17.[Medline]
7. Collins VP, Loeffler RK, Tivey H. Observations on growth rates of human tumors. AJR 1956;76:988–1000.
8. Nathan MH, Collins VP, Adams RA. Differentiation of benign and malignant pulmonary nodules by growth rate. Radiology 1962;79:221–32.[Medline]
9. Steele JD, Buell P. Asymptomatic solitary pulmonary nodules: host survival, tumor size and growth rate. J Thorac Cardiovasc Surg 1973;65:140–51.[Medline]
10. Lillington GA. Management of solitary pulmonary nodules. Dis Month 1991:273–318.
11. Nathan MH. Management of solitary pulmonary nodules: an organized approach based on growth rate statistics. JAMA 1974;227:1141–4.[Medline]
12. Warburg O, Wind F, Negleis E. On the metabolism of tumors in the body. In: Warburg O, ed. The metabolism of tumours. London: Constable, 1930:254–70.
13. Gallagher BM, Fowler JS, Gutterson NI. Metabolic trapping as a principle of radiopharmaceutical design: some factors responsible for the biodistribution of (¹⁸F) 2-deoxy-2-fluoro-D-glucose. J Nucl Med 1978;19:1154–61.[Abstract/Free Full Text]
14. Abe Y, Matsuzawa T, Fujiwara T, et al. Clinical assessment of therapeutic effects on cancer using ¹⁸F-2-fluoro-2-deoxy-D-glucose and positron emission tomography: preliminary study of lung cancer. Int J Radiat Oncol Biol Phys 1990;19:1005–10.[Medline]
15. Kubota K, Matsuzawa T, Fujiwara T, et al. Differential diagnosis of lung tumor with positron emission tomography: a prospective study. J Nucl Med 1990;31:1927–33.[Abstract/Free Full Text]
16. Nolop KB, Rhodes CG, Brudin LH, et al. Glucose utilization in vivo by human pulmonary neoplasms. Cancer 1987;60:2682–9.[Medline]
17. DiChiro G, DeLa Paz RL, Brooks RA, et al. Glucose utilization of cerebral gliomas measured by 18-F-fluoro-deoxyglucose and positron emission tomography. Neurology 1982;32:1323–9.[Abstract/Free Full Text]
18. Minn H, Joensuu H, Ahonen A. Fluorodeoxyglucose imaging: a method to assess the proliferative activity of human cancer in vivo. Comparison with DNA flow cytometry in head and neck tumors. Cancer 1988;61:1776–81.[Medline]
19. Okada J, Yoshikawa K, Itami M, et al. Positron emission tomography using fluorine-18-fluorodeoxyglucose in malignant lymphoma: a comparison with proliferative activity. J Nucl Med 1992;33:325–9.[Abstract/Free Full Text]
20. Scott WL, Schwabe JL, Gupta NC, et al. Positron emission tomography of lung tumors and mediastinal lymph nodes using [¹⁸F] fluorodeoxyglucose. Ann Thorac Surg 1994;58:698–703.[Abstract]
21. Khouri NF, Stitik FP, Erozan YS, et al. Transthoracic needle aspiration biopsy of benign and malignant lung lesions. AJR 1985;144:281–8.[Abstract/Free Full Text]
22. Sanders C. Transthoracic needle aspiration. Clin Chest Med 1992;13:11–6.[Medline]
23. Fletcher EC, Levin DC. Flexible fiberoptic bronchoscopy and fluoroscopically guided transbronchial biopsy in the management of solitary pulmonary nodules. West J Med 1982;136:477–83.[Medline]
24. Wallace JM, Deutsch AL. Flexible fiberoptic bronchoscopy and percutaneous needle lung aspiration for evaluating the solitary pulmonary nodule. Chest 1982;81:665–71.[Abstract]

This article has been cited by other articles:

				B. Goudarzi, H. A. Jacene, and R. L. Wahl Diagnosis and Differentiation of Bronchioloalveolar Carcinoma from Adenocarcinoma with Bronchioloalveolar Components with Metabolic and Anatomic Characteristics Using PET/CT J. Nucl. Med., October 1, 2008; 49(10): 1585 - 1592. [Abstract] [Full Text] [PDF]

				D. Uesaka, Y. Demura, T. Ishizaki, S. Ameshima, I. Miyamori, M. Sasaki, Y. Fujibayashi, and H. Okazawa Evaluation of Dual-Time-Point 18F-FDG PET for Staging in Patients with Lung Cancer J. Nucl. Med., October 1, 2008; 49(10): 1606 - 1612. [Abstract] [Full Text] [PDF]

				I. I. Na, B. H. Byun, H. J. Kang, G. J. Cheon, J. S. Koh, C. H. Kim, D. H. Choe, B.-Y. Ryoo, J. C. Lee, S. M. Lim, et al. 18F-Fluoro-2-Deoxy-Glucose Uptake Predicts Clinical Outcome in Patients with Gefitinib-Treated Non-Small Cell Lung Cancer Clin. Cancer Res., April 1, 2008; 14(7): 2036 - 2041. [Abstract] [Full Text] [PDF]

				J. K. Hoang, L. F. Hoagland, R. E. Coleman, A. D. Coan, J. E. Herndon II, and E. F. Patz Jr Prognostic Value of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography Imaging in Patients With Advanced-Stage Non-Small-Cell Lung Carcinoma J. Clin. Oncol., March 20, 2008; 26(9): 1459 - 1464. [Abstract] [Full Text] [PDF]

				P. Cronin, B. A. Dwamena, A. M. Kelly, and R. C. Carlos Solitary Pulmonary Nodules: Meta-analytic Comparison of Cross-sectional Imaging Modalities for Diagnosis of Malignancy Radiology, March 1, 2008; 246(3): 772 - 782. [Abstract] [Full Text] [PDF]

				M. M. Wahidi, J. A. Govert, R. K. Goudar, M. K. Gould, and D. C. McCrory Evidence for the Treatment of Patients With Pulmonary Nodules: When Is It Lung Cancer?: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition) Chest, September 1, 2007; 132(3_suppl): 94S - 107S. [Abstract] [Full Text] [PDF]

				R. J. Downey, T. Akhurst, M. Gonen, B. Park, and V. Rusch Fluorine-18 fluorodeoxyglucose positron emission tomographic maximal standardized uptake value predicts survival independent of clinical but not pathologic TNM staging of resected non-small cell lung cancer J. Thorac. Cardiovasc. Surg., June 1, 2007; 133(6): 1419 - 1427. [Abstract] [Full Text] [PDF]

				W. A. Weber, J. Czernin, and M. E. Phelps Prognostic Significance of Fluorodeoxyglucose Uptake in Non-Small Cell Lung Cancer. A Blurry Picture? Clin. Cancer Res., June 1, 2007; 13(11): 3105 - 3106. [Full Text] [PDF]

				K.-H. Lee, S.-H. Lee, D.-W. Kim, W. J. Kang, J.-K. Chung, S.-A. Im, T.-Y. Kim, Y. W. Kim, Y.-J. Bang, and D. S. Heo High fluorodeoxyglucose uptake on positron emission tomography in patients with advanced non-small cell lung cancer on platinum-based combination chemotherapy. Clin. Cancer Res., July 15, 2006; 12(14): 4232 - 4236. [Abstract] [Full Text] [PDF]

				B. A. Howard, R. Furumai, M. J. Campa, Z. N. Rabbani, Z. Vujaskovic, X.-F. Wang, and E. F. Patz Jr. Stable RNA Interference-Mediated Suppression of Cyclophilin A Diminishes Non-Small-Cell Lung Tumor Growth In vivo Cancer Res., October 1, 2005; 65(19): 8853 - 8860. [Abstract] [Full Text] [PDF]

				R. M. Lindell, T. E. Hartman, S. J. Swensen, J. R. Jett, D. E. Midthun, M. A. Nathan, and V. J. Lowe Lung Cancer Screening Experience: A Retrospective Review of PET in 22 Non-Small Cell Lung Carcinomas Detected on Screening Chest CT in a High-Risk Population Am. J. Roentgenol., July 1, 2005; 185(1): 126 - 131. [Abstract] [Full Text] [PDF]

				F. C. Detterbeck, J. F. Vansteenkiste, D. E. Morris, C. A. Dooms, A. H. Khandani, and M. A. Socinski Seeking a Home for a PET, Part 3: Emerging Applications of Positron Emission Tomography Imaging in the Management of Patients With Lung Cancer Chest, November 1, 2004; 126(5): 1656 - 1666. [Abstract] [Full Text] [PDF]

				L. Schrevens, N. Lorent, C. Dooms, and J. Vansteenkiste The Role of PET Scan in Diagnosis, Staging, and Management of Non-Small Cell Lung Cancer Oncologist, November 1, 2004; 9(6): 633 - 643. [Abstract] [Full Text] [PDF]

				A. K. Buck, G. Glatting, and S. N. Reske Quantification of 18F-FDG Uptake in Non-Small Cell Lung Cancer: A Feasible Prognostic Marker? J. Nucl. Med., August 1, 2004; 45(8): 1274 - 1276. [Full Text] [PDF]

				E. M. Kamel, D. Zwahlen, M. T. Wyss, K. D. Stumpe, G. K. von Schulthess, and H. C. Steinert Whole-Body 18F-FDG PET Improves the Management of Patients with Small Cell Lung Cancer J. Nucl. Med., December 1, 2003; 44(12): 1911 - 1917. [Abstract] [Full Text] [PDF]

				C. E. Reed General thoracic surgery and the Southern Thoracic Surgical Association: the second 25 years Ann. Thorac. Surg., November 1, 2003; 76(90050): S14 - 16. [Full Text] [PDF]

				M. K. Gould, G. D. Sanders, P. G. Barnett, C. E. Rydzak, C. C. Maclean, M. B. McClellan, and D. K. Owens Cost-Effectiveness of Alternative Management Strategies for Patients with Solitary Pulmonary Nodules Ann Intern Med, May 6, 2003; 138(9): 724 - 735. [Abstract] [Full Text] [PDF]

				Y. Demura, T. Tsuchida, T. Ishizaki, S. Mizuno, Y. Totani, S. Ameshima, I. Miyamori, M. Sasaki, and Y. Yonekura 18F-FDG Accumulation with PET for Differentiation Between Benign and Malignant Lesions in the Thorax J. Nucl. Med., April 1, 2003; 44(4): 540 - 548. [Abstract] [Full Text] [PDF]

				R. J. Downey, T. Akhurst, D. Ilson, R. Ginsberg, M. S. Bains, M. Gonen, H. Koong, M. Gollub, B. D. Minsky, M. Zakowski, et al. Whole Body 18FDG-PET and the Response of Esophageal Cancer to Induction Therapy: Results of a Prospective Trial J. Clin. Oncol., February 1, 2003; 21(3): 428 - 432. [Abstract] [Full Text] [PDF]

				N. Hollings and P. Shaw Diagnostic imaging of lung cancer Eur. Respir. J., April 1, 2002; 19(4): 722 - 742. [Abstract] [Full Text] [PDF]

				H. A. Nabi and J. M. Zubeldia Clinical Applications of 18F-FDG in Oncology J. Nucl. Med. Technol., March 1, 2002; 30(1): 3 - 9. [Abstract] [Full Text] [PDF]

				K. Higashi, Y. Ueda, Y. Arisaka, T. Sakuma, Y. Nambu, M. Oguchi, H. Seki, S. Taki, H. Tonami, and I. Yamamoto 18F-FDG Uptake as a Biologic Prognostic Factor for Recurrence in Patients with Surgically Resected Non-Small Cell Lung Cancer J. Nucl. Med., January 1, 2002; 43(1): 39 - 45. [Abstract] [Full Text] [PDF]

				K. Higashi, Y. Ueda, T. Sakuma, H. Seki, M. Oguchi, M. Taniguchi, S. Taki, H. Tonami, S. Katsuda, and I. Yamamoto Comparison of [18F]FDG PET and 201Tl SPECT in Evaluation of Pulmonary Nodules J. Nucl. Med., October 1, 2001; 42(10): 1489 - 1496. [Abstract] [Full Text] [PDF]

				A. Imdahl, S. Jenkner, I. Brink, E. Nitzsche, E. Stoelben, E. Moser, and J. Hasse Validation of FDG positron emission tomography for differentiation of unknown pulmonary lesions Eur. J. Cardiothorac. Surg., August 1, 2001; 20(2): 324 - 329. [Abstract] [Full Text] [PDF]

				S. S. Gambhir, J. Czernin, J. Schwimmer, D. H. S. Silverman, R. E. Coleman, and M. E. Phelps A Tabulated Summary of the FDG PET Literature J. Nucl. Med., May 1, 2001; 42(90050): 1S - 93. [Full Text] [PDF]

				J.F. Vansteenkiste and S.G. Stroobants The role of positron emission tomography with 18F-fluoro-2-deoxy-D-glucose in respiratory oncology Eur. Respir. J., April 1, 2001; 17(4): 802 - 820. [Abstract] [Full Text] [PDF]

				M. K. Gould, C. C. Maclean, W. G. Kuschner, C. E. Rydzak, and D. K. Owens Accuracy of Positron Emission Tomography for Diagnosis of Pulmonary Nodules and Mass Lesions: A Meta-analysis JAMA, February 21, 2001; 285(7): 914 - 924. [Abstract] [Full Text] [PDF]

				K. Dhital, C. A.B. Saunders, P. T. Seed, M. J. O'Doherty, and J. Dussek [18F]Fluorodeoxyglucose positron emission tomography and its prognostic value in lung cancer Eur. J. Cardiothorac. Surg., October 1, 2000; 18(4): 425 - 428. [Abstract] [Full Text] [PDF]

				H. Vesselle, R. A. Schmidt, J. M. Pugsley, M. Li, S. G. Kohlmyer, E. Vallières, and D. E. Wood Lung Cancer Proliferation Correlates with [F-18]Fluorodeoxyglucose Uptake by Positron Emission Tomography Clin. Cancer Res., October 1, 2000; 6(10): 3837 - 3844. [Abstract] [Full Text]

				D. OST and A. FEIN Evaluation and Management of the Solitary Pulmonary Nodule Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 782 - 787. [Full Text]

				V. J. Lowe, J. H. Boyd, F. R. Dunphy, H. Kim, T. Dunleavy, B. T. Collins, D. Martin, B. C. Stack Jr, C. Hollenbeak, and J. W. Fletcher Surveillance for Recurrent Head and Neck Cancer Using Positron Emission Tomography J. Clin. Oncol., February 1, 2000; 18(3): 651 - 651. [Abstract] [Full Text] [PDF]

				H. Sakurai, N. Mitsuhashi, K. Hayakawa, and H. Niibe Giant Cell Tumor of the Thoracic Spine Simulating Mediastinal Neoplasm AJNR Am. J. Neuroradiol., October 1, 1999; 20(9): 1723 - 1726. [Abstract] [Full Text]

				J. F. Vansteenkiste, S. G. Stroobants, P. J. Dupont, P. R. De Leyn, E. K. Verbeken, G. J. Deneffe, L. A. Mortelmans, and M. G. Demedts Prognostic Importance of the Standardized Uptake Value on 18F-Fluoro-2-Deoxy-Glucose–Positron Emission Tomography Scan in Non–Small-Cell Lung Cancer: An Analysis of 125 Cases J. Clin. Oncol., October 1, 1999; 17(10): 3201 - 3206. [Abstract] [Full Text] [PDF]

				C. A.B. Saunders, J. E. Dussek, M. J. O'Doherty, and M. N. Maisey Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer Ann. Thorac. Surg., March 1, 1999; 67(3): 790 - 797. [Abstract] [Full Text] [PDF]

				V. J Lowe and K. S Naunheim Current role of positron emission tomography in thoracic oncology Thorax, August 1, 1998; 53(8): 703 - 712. [Full Text]