The likelihood for a surgical cure of newly-diagnosed primary non-small cell lung cancers is strongly dependent upon the local extent of the cancer, particularly whether or not the mediastinal lymph nodes are involved with cancer. Five year survivals of approximately 8% ar seen in patients whose mediastinal lymph nodes are involved with cancer vs. 46% when there are no mediastinal metastases. The potentially curative surgical procedures of thoracotomy with lobectomy or pneumonectomy cause substantial mortality (+5%) and morbidity (+10%) and are inappropriate of the patients disease burden is so extensive as to be non-resectable and non-curable. While standard cross-sectional imaging methods such as CT or MRI are routinely used pre-operatively for staging, recent studies have demonstrated that these methods are: 1) incapable of detecting small foci of metastatic cancer in mediastinal lymph nodes that are not enlarged, and 20 incapable of specifically determining whether borderline or moderately-enlarged mediastinal lymph nodes are involved with cancer. Thus, the sensitivity and specificity of these cross-sectional methods are not optimal. We propose to prospectively evaluate the accuracy of pre-operative PET scanning using FDG and 11C-L- methionine for the detection of mediastinal tumor metastases in patients with newly- diagnosed non-small cell lung cancers. CT and PET scans performed on such patients prior to surgery will first be interpreted separately, then the CT and PET scans will be interpreted together. In addition, the CT and PET images will be co-registered using computer image fusion methods and a series of anatomic/metabolic fusion images produced. These metabolic/anatomic fusion images will also be interpreted to enhance the anatomic localization and diagnostic accuracy of the PET staging procedure. Patients will also receive an i.v. tracer injection of FDG immediately prior to surgery, so that the uptake of FDG can be measured in biopsy specimens containing tumor-involved and normal tissues. Thoracic surgery, specifically sampling well-defined American Thoracic Society designated mediastinal nodal regions, will be performed. Nodal histology and FDG uptake in the resected cancers and lymph nodes will be determined and correlated with the presence or absence of cancer. The accuracy of CT and PET interpreted independently, and then together both with, and without, the metabolic/anatomic fusion images, will then be compared to pathological 'truth'. These results will then be used to develop and optimize interpretative criteria for PET in the staging of the mediastinum in patients with non-small cell lung cancer. These criteria will be applied prospectively to patients imaged in the third and fourth year of the proposal. Through this study we expect to determine the accuracy, and thus the potential diagnostic utility, of FDG and 11C-L-methionine PET scanning in the pre-operative staging of patients with non-small cell lung cancers.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
Zip Code
Barglow, Katherine T; Knutson, Charles G; Wishnok, John S et al. (2011) Site-specific and redox-controlled S-nitrosation of thioredoxin. Proc Natl Acad Sci U S A 108:E600-6
Minn, H; Clavo, A C; Fisher, S J et al. (2000) Effect of nitroimidazole sensitizers on in vitro glycolytic metabolism of hypoxic squamous cell carcinoma. Acta Oncol 39:199-205
Torizuka, T; Zasadny, K R; Kison, P V et al. (2000) Metabolic response of non-Hodgkin's lymphoma to 131I-anti-B1 radioimmunotherapy: evaluation with FDG PET. J Nucl Med 41:999-1005
Sugawara, Y; Gutowski, T D; Fisher, S J et al. (1999) Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, L-methionine, 67Ga-citrate, and 125I-HSA. Eur J Nucl Med 26:333-41
Shreve, P D; Anzai, Y; Wahl, R L (1999) Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics 19:61-77;quiz 150-1
Brown, R S; Leung, J Y; Kison, P V et al. (1999) Glucose transporters and FDG uptake in untreated primary human non-small cell lung cancer. J Nucl Med 40:556-65
Sugawara, Y; Zasadny, K R; Grossman, H B et al. (1999) Germ cell tumor: differentiation of viable tumor, mature teratoma, and necrotic tissue with FDG PET and kinetic modeling. Radiology 211:249-56
Sugawara, Y; Fisher, S J; Zasadny, K R et al. (1998) Preclinical and clinical studies of bone marrow uptake of fluorine-1-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy. J Clin Oncol 16:173-80
Macfarlane, D J; Sondak, V; Johnson, T et al. (1998) Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography in staging of regional lymph nodes in patients with cutaneous malignant melanoma. J Clin Oncol 16:1770-6
Torizuka, T; Zasadny, K R; Recker, B et al. (1998) Untreated primary lung and breast cancers: correlation between F-18 FDG kinetic rate constants and findings of in vitro studies. Radiology 207:767-74

Showing the most recent 10 out of 23 publications