18F-FSPG PET/CT in Imaging Patients With Newly Diagnosed Lung Cancer or Indeterminate Pulmonary Nodules

Study Overview
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Brief Summary
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This clinical trial compares fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) positron emission tomography (PET)/computed tomography (CT) to the standard of care fluorodeoxyglucose F-18 (18F-FDG) PET/CT in imaging patients with newly diagnosed lung cancer or indeterminate pulmonary nodules. PET/CT uses a radioactive glutamate (one of the common building blocks of protein) called 18F-FSPG which may be able to recognize differences between tumor and healthy tissue. Since tumor cells are growing, they need to make protein, and other building blocks, for cell growth that are made from glutamate and other molecules. PET/CT using a radioactive glutamate may be a more effective method of diagnosing lung cancer than the standard PET/CT using a radioactive glucose (sugar), such as 18F-FDG.

Detailed Description
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PRIMARY OBJECTIVES: I. To compare the imaging characteristics of 18F-FSPG PET/CT with standard-of-care, 18F-FDG PET/CT. II. To compare the imaging characteristics of 18F-FSPG PET/CT to standard-of-care 18F-FDG PET/CT in patients with newly diagnosed lung cancer. III. To determine whether 18F-FSPG uptake in lung cancer can be predicted based on correlation with CD44 and amino acid transport system xc- (xC-) expression in surgical pathology specimens. OUTLINE: Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. After completion of study, patients are followed up for 2 years if needed for diagnosis.

Official Title
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PET Imaging of Lung Cancer and Indeterminate Pulmonary Nodules With 18F-FSPG

Conditions
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Lung Carcinoma, Solitary Pulmonary Nodule, Cigarette Smoking Behavior

Intervention / Treatment
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* Procedure: Computed Tomography
* Procedure: Computed Tomography
* Radiation: fluorodeoxyglucose F-18
* Drug: Fluorine F 18 L-glutamate Derivative BAY94-9392
* Other: Laboratory Biomarker Analysis
* Procedure: Positron Emission Tomography
* Procedure: Positron Emission Tomography (PET)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Have an indeterminate untreated pulmonary nodule (IPN) (7-30 mm diameter) on CT, or an indeterminate lung mass (> 30 mm diameter), without prior examinations that establish that the lesion has been stable for two or more years, untreated. or Have a newly diagnosed, untreated primary lung cancer diameter 7 mm or more. Be able to give informed consent, which will include a layman's explanation of the estimated amount of additional radiation that the patient will receive from the investigational PET/CT scan using 18F-FSPG Must agree at the time of study entry to undergo clinically indicated biopsy(ies) or a 24-month period of follow-up, as needed, to resolve the etiology of their IPN(s) or lung mass(es). Exclusion Criteria: Pregnant or lactating patients will be excluded, as will females of childbearing potential who refuse to undergo a serum or urinary beta-HCG pregnancy test the day of either the 18F-FSPG or the 18F-FDG PET/CT scans, in accordance with the standard policy of the Medical Imaging Service at our facility. Women who have experienced 24 consecutive months of amenorrhea, have reached at least 60 years of age, or have had a tubal ligation or hysterectomy documented in their medical records are considered not to be of childbearing potential for the purposes of this protocol Patients with a body weight of 400 pounds or more or a body habitus or disability that will not permit the imaging protocol to be performed A recognized active lung infection Previous systemic or radiation treatment for cancer of any type within 1 year For patients who do not have a tissue diagnosis: Non-oncologic severe co-morbidities suggesting a life span of less than two years if not treated, as determined by the potential subject's treating physician.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)<br>Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. | Procedure: Computed Tomography<br>* Undergo 18F-FDG PET/CT - standard of care<br>* Other names: tomography;Procedure: Computed Tomography<br>* Undergo 18F-FSPG PET/CT<br>* Other names: tomography;Radiation: fluorodeoxyglucose F-18<br>* Undergo 18F-FDG PET/CT - standard of care<br>* Other names: Fluorine-18 2-Fluoro-2-deoxy-D-Glucose;Drug: Fluorine F 18 L-glutamate Derivative BAY94-9392<br>* Undergo 18F-FSPG PET/CT<br>* Other names: BAY94-9392;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Positron Emission Tomography<br>* Undergo 18F-FDG PET/CT - standard of care<br>* Other names: proton magnetic resonance spectroscopic imaging;Procedure: Positron Emission Tomography (PET)<br>* Undergo 18F-FSPG PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | Sensitivity, specificity, overall accuracy and receiver operating characteristic (ROC) curves will be generated and compared for both 18F-FDG and 18F-FSPG tests. Sensitivity is the proportion of High(positive) among cancer patients. Specificity is the proportion of low(negative) among benign tumors. Accuracy is the proportion of correctly diagnosed among analyzed patients. Area under the curve(AUC) is the area under the ROC curve, which is the plot of sensitivity by 1-specificity. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD44 and xC- Expression Levels in Tissue Samples(0-3) | The level of expression of xCT and CD44 proteins in the cytoplasmic membrane of tumor cells were examined by an experienced pathologist who was blinded to any patient and imaging information. The percentage of tumor cells positive for the marker and the intensity of staining were evaluated, the latter using a scale of 0 (none), 1+ (weak), 2+ (intermediate), and 3+ (strong) with a sample being reported as positive if greater than 10% of the tumor cells in the sample were positively stained with any intensity. | Up to 2 years | 
| Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the Tumor) | Maximum standardized uptake values (SUVmax) were normalized to lean body mass and measured with a 1 cm diameter round region of interest over the area of greatest uptake in the lesion being measured. | Up to 2 years | 
| Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | Sensitivity, specificity, overall accuracy and ROC curves will be generated and compared for both 18F-FDG and 18F-FSPG tests. Wilcoxon rank-sum or Kruskal-Wallis tests will be applied for the group comparisons of the biodistribution characteristics of 18F-FDG and 18F-FSPG tests. Sensitivity is the proportion of High(positive) among cancer patients. Specificity is the proportion of low(negative) among benign tumors. Accuracy is the proportion of correctly diagnosed among all patients. Area under the curve(AUC) is the area under the ROC curve. | Up to 2 years |