Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules.

BACKGROUND: Effective strategies for managing patients with solitary pulmonary nodules (SPN) depend critically on the pre-test probability of malignancy. OBJECTIVE: To validate two previously developed models that estimate the probability that an indeterminate SPN is malignant, based on clinical characteristics and radiographic findings. METHODS: Data on age, smoking and cancer history, nodule size, location and spiculation were collected retrospectively from the medical records of 151 veterans (145 men, 6 women; age range 39-87 years) with an SPN measuring 7-30 mm (inclusive) and a final diagnosis established by histopathology or 2-year follow-up. Each patient's final diagnosis was compared with the probability of malignancy predicted by two models: one developed by investigators at the Mayo Clinic and the other developed from patients enrolled in a VA Cooperative Study. The accuracy of each model was assessed by calculating areas under the receiver operating characteristic (ROC) curve and the models were calibrated by comparing predicted and observed rates of malignancy. RESULTS: The area under the ROC curve for the Mayo Clinic model (0.80; 95% CI 0.72 to 0.88) was higher than that of the VA model (0.73; 95% CI 0.64 to 0.82), but this difference was not statistically significant (Delta = 0.07; 95% CI -0.03 to 0.16). Calibration curves showed that the probability of malignancy was underestimated by the Mayo Clinic model and overestimated by the VA model. CONCLUSIONS: Two existing prediction models are sufficiently accurate to guide decisions about the selection and interpretation of subsequent diagnostic tests in patients with SPNs, although clinicians should also consider the prevalence of malignancy in their practice setting when choosing a model.

Characterization of delta opioid receptors in lung cancer using a novel nonpeptidic ligand.

Cancer cells are often characterized by the presence of membrane receptors not normally associated with nontransformed cells from the same tissue type. Recent studies have demonstrated increased expression of high-affinity binding sites for opioid receptor-selective ligands in lung cancer cell lines relative to normal lung tissue. We investigated the binding of a nonpeptidic delta opioid receptor ligand in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cells with the aim of developing the ligand as a novel lung cancer imaging agent. The ligand, [3H] (+)-4-[alpha-R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N-diethylbenzamide ([3H](+)BW373U86), bound with high-affinity [Kd (dissociation constant) = 0.066 +/- 0.012 nM] to membranes prepared from six different SCLC cell lines but not to those from seven NSCLC cell lines, including one mesothelioma. The number of biding sites varied from 10 to 300 fmol/mg membrane protein. Competition binding studies demonstrated displacement of [3H](+)BW373U86 binding by the delta-selective antagonists naltriben and 7-benzylidenenaltrexone but not with the mu- and kappa- selective antagonists D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 and trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]ben zeneacetamide methanesulfonate. Mean apparent Kis for naltriben and 7-benzylidenenaltrexone in membranes from two SCLC cell lines were 0.17 and 3.9 nM, respectively, but were >10 microM for the mu and kappa ligands. The nonselective antagonist naloxone displaced [3H](+)BW373U86 binding with an apparent Ki of approximately 29 nM. On the basis of these data, we believe the lung cancer receptor to be similar, if not identical, to the human brain delta opioid receptor. The lack of high-affinity [3H](+)BW373U86 binding in normal mouse lung membranes suggests a potential role for this ligand as a novel therapeutic or imaging agent.

Prospective investigation of positron emission tomography in lung nodules.

PURPOSE: Solitary pulmonary nodules (SPNs) are commonly identified by chest radiographs and computed tomography (CT). Biopsies are often performed to evaluate the nodules further. An accurate, noninvasive diagnostic test could avoid the morbidity and costs of invasive tissue sampling. We evaluated the ability of fluorine-18 deoxyglucose positron emission tomography (FDG-PET) to discriminate between benign and malignant pulmonary nodules in a prospective, multicenter trial. METHODS: Eighty-nine patients who had newly identified indeterminate SPNs on chest radiographs and CT were evaluated with FDG-PET. PET data were analyzed semiquantitatively by calculating standardized uptake values (SUVs) as an index of FDG accumulation and also by a visual scoring method. PET results were compared with pathology results. RESULTS: Sixty SPNs were malignant and 29 were benign. Using SUV data, PET had an overall sensitivity and specificity for detection of malignant nodules of 92% and 90%. Visual analysis provided a slightly higher, but not statistically significant, sensitivity of 98% and lower specificity of 69%. For SPNs < or = 1.5 cm (34 of 89), the sensitivity and specificity of SUV and visual analysis were 80% and 95% and 100% and 74%, respectively. CONCLUSION: FDG-PET can accurately characterize indeterminate SPNs. PET imaging provides a noninvasive method to evaluate indeterminate SPNs, which can reduce the need for invasive tissue biopsy.

Imaging lung cancer.

Imaging plays an essential role in diagnosing, staging, and following patients with lung cancer. Most tumors are found on chest radiographs, although further evaluation with thoracic computed tomography is performed to stage local disease. Additional radiologic studies, including radionuclide bone scan, brain computed tomography, or magnetic resonance imaging are typically used in select patients in the search for extrathoracic metastases. More recently, whole body positron emission tomography imaging has become an extremely useful tool in evaluating the primary tumor, regional lymph nodes, and distant sites of disease in lung cancer patients. With continued improvements in diagnostic imaging modalities, definition of risk groups, discovery of molecular markers, and development of new therapeutic strategies, improved survival rates should result in the future. This review focuses on the current imaging techniques used to evaluate patients with lung cancer.

Semiquantitative and visual analysis of FDG-PET images in pulmonary abnormalities.

UNLABELLED: FDG PET images of the thorax can be analyzed semiquantitatively using standardized uptake ratios (SUR) or activity ratios between abnormal and normal tissue, or qualitatively by visual comparison of the abnormality to normal structures. Standardized uptake ratio evaluation of FDG PET images has been shown to accurately differentiate benign from malignant focal pulmonary abnormalities. The accuracy of activity ratios and visual analysis have not been evaluated. We therefore prospectively analyzed FDG PET images in patients with pulmonary abnormalities to evaluate differences in analytic schemes. METHODS: We evaluated 107 patients with an indeterminate focal abnormality on chest radiograph or CT with FDG PET between November 1991 and March 1993. The PET studies were evaluated using SUR, activity ratios and visual analysis. Activity ratios of maximum activity/cc and average activity/cc between regions of interest (ROIs) in abnormalities and normal lung on the contralateral side were calculated. Visual interpretations were graded on a five-point scale of two observers' confidence of malignancy. FDG uptake in the abnormality was also visually graded in comparison to mediastinal activity. Receiver-operating characteristic (ROC) curve areas were generated for the SUR data, activity ratios and visual analysis. RESULTS: Of 88 patients in which a conclusive diagnosis was made, 61 (69%) patients had malignancy and 27 (31%) patients had a benign process. SUR, maximum activity ratio, average activity ratio and visual interpretation ROC curve areas were 0.96, 0.95, 0.92 and 0.96, respectively. CONCLUSIONS: SUR, activity ratios and visual evaluation are each equally accurate methods of FDG PET data analysis in differentiating malignant from benign focal pulmonary abnormalities.

Imaging bronchogenic carcinoma.

Imaging plays an integral role in diagnosing, staging, and following patients with lung cancer. Most lung tumors are detected on chest radiographs, but unfortunately, the majority of patients have advanced stage disease at presentation. There is a wide spectrum of radiologic manifestations of lung cancer, and recognition of these findings is essential for patient management. As we continue to understand more about tumor biology, new imaging techniques should emerge and have the potential to significantly improve our diagnostic capabilities.

Malignant pleural effusions: recent advances and ambulatory sclerotherapy.

Malignant pleural effusions are a common problem in cancer patients with advanced disease. Patients typically present with progressive dyspnea, cough, and/or chest pain that significantly compromises their quality of life. Treatment is often palliative, usually consisting of sequential thoracenteses or tube thoracostomy with or without sclerotherapy. The traditional method of treatment--tube thoracostomy with large-bore chest tubes connected to continuous wall suction--requires hospitalization, is expensive, limits patient mobility, and can cause significant patient discomfort. More recent trials have explored new techniques, including thoracoscopic insufflation of talc and small-bore catheters. Most of these studies have been performed on inpatients, although a recent multi-institutional trial was initiated to evaluate the feasibility and efficacy of ambulatory (outpatient) pleural drainage and sclerotherapy using small-bore catheters. All patients fulfilling eligibility criteria had a small-bore catheter placed in the pleural space that was then connected to a closed gravity drainage bag system. When daily tube drainage was <100 mL, sclerotherapy was performed. Response rates at our institution demonstrated 10 patients (53%) had a complete response, 5 (26%) had a partial response, and 4 (21%) had progressive disease at 30-day follow-up. These preliminary results suggest ambulatory sclerotherapy is a safe, viable alternative to conventional inpatient treatment of malignant pleural effusions in a select group of patients.

Significance of percutaneous needle biopsy in patients with multiple pulmonary nodules and a single known primary malignancy.

OBJECTIVE: To determine the necessity of percutaneous lung biopsy in patients with a single known primary malignancy and multiple pulmonary nodules. DESIGN: Retrospective study. SETTING: Tertiary care university hospital. RESULTS: We reviewed all percutaneous lung biopsy specimens over a 6-year period. One hundred forty-six patients with a single known primary malignancy and multiple pulmonary nodules had biopsies performed up to 19 years following diagnosis of the primary neoplasm. One hundred thirty-seven biopsy specimens (93.8%) were positive for metastases. Eight patients (5.5%) had a nondiagnostic biopsy specimen; however, subsequent imaging studies and the clinical course strongly suggested diffuse metastatic disease. One patient (< 1%) with breast carcinoma developed nodules 3 years after initial diagnosis and had resolution without a definitive diagnosis or therapy. CONCLUSION: Patients with a single known primary malignancy and multiple pulmonary nodules who present for percutaneous needle biopsy will have pulmonary metastases in the vast majority of cases. Biopsy in these patients rarely changes the clinical course as other diagnoses are rarely established.

Cytologically proved malignant pleural effusions: distribution of transudates and exudates.

PURPOSE: This study attempts to determine the distribution of transudates vs exudates in pathologically proved malignant pleural effusions and the necessity for cytologic studies in patients with a transudative effusion. MATERIALS AND METHODS: A retrospective review of all cytologically positive malignant pleural effusions was performed at Duke University Medical Center over an 18-month period. All effusions were characterized as a transudate or an exudate based on standard criteria, including lactate dehydrogenase and protein values. RESULTS: Ninety-eight patients with a mean age of 62 years were identified as having a cytologically positive malignant pleural effusion and blood chemistry values available to distinguish an exudate from transudate. Ninety-seven patients (99%, 95% confidence interval; 0.94 to 0.99) had criteria for an exudative effusion. One patient (1%) with diffuse metastatic lung cancer had a borderline transudate and was in congestive heart failure at the time of thoracentesis. CONCLUSIONS: Cytologically positive pleural effusions for malignancy are almost always exudates. Cytologic evaluation for malignant cells of a transudative pleural effusion is not recommended.

Thoracic nodal staging with PET imaging with 18FDG in patients with bronchogenic carcinoma.

PURPOSE: To assess the role of positron emission tomographic (PET) imaging with 18-fluoro-2-deoxyglucose (18FDG) in detecting thoracic lymph node metastases in patients with bronchogenic carcinoma. MATERIALS AND METHODS: Over a 2-year period, any patient presenting to our institution with newly diagnosed bronchogenic carcinoma who was to have thoracic nodes sampled was considered eligible. All PET studies were performed prior to nodal sampling and areas of increased uptake were mapped according to the American Thoracic Society classification. Studies were correlated with CT and pathology. Sensitivity and specificity for predicting nodal metastases was calculated. RESULTS: Forty-two patients had 62 nodal stations (40 hilar/lobar, 22 mediastinal) sampled. The sensitivity and specificity for hilar/lobar lymph node station metastases using PET imaging was 73% and 76%, respectively. With CT, the sensitivity and specificity were 27% and 86%. The sensitivity and specificity using PET imaging for mediastinal node station metastases was 92% and 100%, respectively, while with CT the figures were 58% and 80%. The sensitivity and specificity for combined thoracic nodal station metastases using PET imaging was 83% and 82%, respectively, while with CT it was 43% and 85%. There was a strong statistical relationship between positive PET imaging and lymph node abnormalities. CONCLUSIONS: 18FDG-PET imaging is accurate in detecting thoracic lymph node metastases in patients with bronchogenic carcinoma. Normal results of PET studies virtually preclude the need for mediastinal nodal sampling prior to surgery, whereas abnormal results of studies most likely represent mediastinal metastases. Treatment can be based on the extent of disease suggested by PET imaging.

Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to determine the relationship between tumor size and survival in patients with stage IA non-small cell lung cancer (non-small cell lung cancer; ie, lesions < 3 cm). METHOD: Five hundred ten patients with pathologic stage IA (T1N0M0) non-small cell lung cancer were identified from our tumor registry over an 18-year period (from 1981 to 1999). There were 285 men and 225 women, with a mean age of 63 years (range, 31 to 90 years). The Cox proportional model was used to examine the effect on survival. Tumor size was incorporated into the model as a linear effect and as categorical variables. The Kaplan-Meier product limit estimator was used to graphically display the relationship between the tumor size and survival. RESULTS: The Cox proportional hazards model did not show a statistically significant relationship between tumor size and survival (p = 0.701) as a linear effect. Tumor size was then categorized into quartiles, and again there was no statistically significant difference in survival between groups (p = 0.597). Tumor size was also categorized into deciles, and there was no statistical relationship between tumor size and survival (p = 0.674). CONCLUSIONS: This study confirms stratifying patients with stage IA non-small cell lung cancer in the same TNM classification, given no apparent difference in survival. Unfortunately, these data caution that improved small nodule detection with screening CT may not significantly improve lung cancer mortality. The appropriate prospective randomized trial appears warranted.

Significance of hemoptysis following thrombolytic therapy for acute myocardial infarction.

PURPOSE: To describe the occurrence, cause, and significance of hemoptysis following thrombolytic therapy for acute myocardial infarction. PATIENTS AND METHODS: We retrospectively reviewed 2,634 patients presenting with acute myocardial infarction who received thrombolytic therapy to determine the incidence of hemoptysis. Chart and radiographic review included the type, dose, and route of thrombolytic therapy. In addition, the onset, duration, and severity of hemoptysis were recorded and correlated with radiographic and bronchoscopic findings. RESULTS: Eleven patients (0.4%) developed hemoptysis following administration of thrombolytic therapy for an acute myocardial infarction. The duration and severity had a wide range, although no patient had significant hemodynamic compromise. The source of hemoptysis was identified in only one patient who had a tongue laceration following cardiopulmonary resuscitation, and blood was seen within the oropharynx and trachea. No definitive cause was identified in all other patients. There was no correlation between the different types or doses of thrombolytic therapy and the duration or severity of hemoptysis. Chest radiographs were nonspecific and demonstrated resolution within 11 days following hemoptysis. CT of the thorax in one patient and bronchoscopy in two patients confirmed chest radiographic findings and in no patient was an underlying pulmonary abnormality identified. CONCLUSIONS: Pulmonary hemorrhage and hemoptysis are unusual complications of thrombolytic therapy in patients with acute myocardial infarction. Although hemoptysis may be the first indicator of an underlying pulmonary abnormality, we found no case in which a significant abnormality was unmasked. This study suggests that follow-up chest radiographs are recommended and further evaluation may be unnecessary if complete resolution is demonstrated.

Detection of primary and recurrent lung cancer by means of F-18 fluorodeoxyglucose positron emission tomography (FDG PET).

Positron emission tomography (PET), with the glucose analog F-18 fluoro-deoxyglucose (FDG), takes advantage of the enhanced glucose uptake observed in neoplastic cells. We examined whether the detection of preferential FDG uptake with PET permits differentiation between benign and malignant focal pulmonary lesions in patients with suspected primary or recurrent lung cancer. Between November 1991 and September 1993, 100 patients with indeterminate focal pulmonary abnormalities including 16 patients who had previous lung resections for cancer were prospectively studied. Tissue diagnosis was obtained by transbronchial or percutaneous biopsy (n = 49) and open biopsy or resection (n = 35). Three patients underwent extended observation (> 2 years) alone. Excluded were 13 patients lacking firm pathologic diagnoses and less than 2-year follow-up. FDG activity in the lesion was expressed as a calculated standardized uptake ratio. Mean standardized uptake ratio (+/- standard deviation) was 6.6 (+/- 3.1) in 59 patients with cancer versus 2.0 (+/- 1.6) in 28 with benign disease (p = 0.0001; unpaired t test, two-sided). With a standardized uptake ratio > or = 2.5 used for detecting malignancy, sensitivity, specificity, and accuracy were 97% (57/59), 82% (23/28), and 92% (80/87), respectively. Notably, in patients evaluated for pulmonary abnormalities after lung resection for cancer, all chest recurrences were correctly identified. The exceptional sensitivity of FDG PET demonstrates that malignant pulmonary lesions preferentially accumulate FDG, which results in a standardized uptake ratio > or = 2.5. PET may be useful for distinguishing recurrent tumor from postoperative, or postradiation, changes. If performed in all patients before open biopsy, PET increases the diagnostic yield by reducing the number of patients who have benign lesions at operation. Moreover, by lowering expenditures for hospitalization and other diagnostic procedures, FDG PET may significantly reduce health care costs.

Sclerotherapy for malignant pleural effusions: a prospective randomized trial of bleomycin vs doxycycline with small-bore catheter drainage.

BACKGROUND: Malignant pleural effusions are a common problem for patients with metastatic disease. Most patients are treated with tube thoracostomy and sclerotherapy, although there remains no standard approach. The purpose of this study was to compare the efficacy of bleomycin with doxycycline sclerotherapy for the treatment of malignant pleural effusions using small-bore catheters. METHODS: All patients with a symptomatic malignant pleural effusion referred for chest tube drainage and sclerotherapy over a 2-year period were considered eligible. Using image guidance, a 14F self-retaining catheter was inserted into the pleural space and connected to continuous wall suction. When drainage fell below 200 mL/d, patients were randomized to 60 U of bleomycin or 500 mg of doxycycline sclerotherapy. Response at 30 days was determined. RESULTS: One hundred six patients were enrolled in the study. Fifteen men (29%) and 37 women (71%) with a mean age of 57 years received bleomycin sclerotherapy. Twenty-one of the 29 patients (72%) alive and evaluable at 30 days had successful sclerotherapy. Twenty-three men (43%) and 31 women (57%) with a mean age of 61 years received doxycycline sclerotherapy. Twenty-three of the 29 patients (79%) alive and evaluable at 30 days had successful sclerotherapy. There was no significant difference in response rates between doxycycline and bleomycin (p=0.760). CONCLUSIONS: These data continue to support a role for small-bore chest drainage and sclerotherapy, although there was no significant difference in 30-day response rates between doxycycline and bleomycin.

Identification of small lung nodules at autopsy: implications for lung cancer screening and overdiagnosis bias.

PURPOSE: Unsuspected cases of lung cancer are reported to be uncommon in autopsy series, and these data have been used to suggest that indolent tumors are rare and that overdiagnosis bias is not an important factor in lung cancer screening. The purpose of this study was to determine if a retrospective autopsy review is indeed accurate in identifying all small lung nodules on CT, and thus provide a true estimate of unsuspected lung tumors. MATERIALS AND METHODS: We identified all 1047 patients who had an autopsy at our institution from 1994 to 1998. We then reviewed the patients radiology records and found 187 patients with a thoracic CT within 2 months of the postmortem examination. All 187 CT reports were reviewed in order to identify patients with at least one pulmonary nodule. CT studies with reports that described a nodule(s) were then re-reviewed to confirm presence and location of the nodule(s). The CT findings were than compared to the autopsy report to determine if the postmortem examination indeed found the nodule(s). RESULTS: 28 autopsy patients had at least one pulmonary nodule identified on their thoracic CT no more than 2 months before death. Nineteen patients (68%) had nodule(s) recorded on the autopsy report, two ( approximately 10%) of which proved to have undiagnosed squamous cell carcinoma. Nine patients (22%) had no mention of pulmonary nodules seen on the CT recorded on their autopsy report. CONCLUSIONS: This study suggests autopsies do not identify all small pulmonary nodules found at CT. The true incidence of clinically insignificant lung cancer is thus uncertain, and overdiagnosis bias in lung cancer screening may be more important than previously recognized.

Lung cancer and positron emission tomography with fluorodeoxyglucose.

Over the past years, positron emission tomography (PET) with fluoro-2-deoxy-D-glucose (FDG) has emerged as an important imaging modality. In the thorax, FDG-PET has been shown to differentiate benign from malignant pulmonary lesions and stage lung cancer. Preliminary studies have shown its usefulness in assessing tumor recurrence, and assisting in radiotherapy planning. FDG-PET is often more accurate than conventional imaging studies, and has been proven to be cost-effective in evaluating lung cancer patients. This review will discuss the current applications of FDG-PET as compared with conventional imaging in diagnosing, staging, and following patients with lung cancer.

Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer.

PURPOSE: To correlate FDG activity on PET with the expression of glucose transporter proteins Glut-1 and Glut-3 in patients with early stage non-small cell lung cancer (NSCLC). METHODS: Over a 5 year period, all patients with a PET scan and clinical stage I NSCLC underwent an immunohistochemical analysis of their tumor for Glut-1 and Glut-3 expression. The amount of FDG uptake in the primary lesion was measured by a standardized uptake ratio (SUR) and correlated with immunohistochemical results. RESULTS: Seventy-three patients with a mean age of 66 years had clinical stage I disease. The final pathologic stage showed 64 patients with stage IA/B disease, eight with stage IIA disease, and one patient with pathologic stage IIIA (T1N2) disease. Glut-1 transporter expression was significantly higher than Glut-3 (P<0.0001), and although there was some association between the SUR and Glut-1 (P=0.085) and SUR and Glut-3 (P=0.074) expression, this did not reach statistical significance. CONCLUSIONS: Glut-1 and Glut-3 transporter expression did not demonstrate a statistically significant correlation with FDG uptake in potentially resectable lung cancer. It appears that these transporters alone do not affect the variation in FDG activity in early stage NSCLC.

Multimodality nuclear medicine imaging in three-dimensional radiation treatment planning for lung cancer: challenges and prospects.

The purpose of this study was to determine the utility of quantitative single photon emission computed tomography (SPECT) lung perfusion scans and F-18 fluorodeoxyglucose positron emission computed tomography (PET) during X-ray computed tomography (CT)-based treatment planning for patients with lung cancer. Pre-radiotherapy SPECT (n = 104) and PET (n = 35) images were available to the clinician to assist in radiation field design for patients with bronchogenic cancer. The SPECT and PET scans were registered with anatomic information derived from CT. The information from SPECT and PET provides the treatment planner with functional data not seen with CT. SPECT yields three-dimensional (3D) lung perfusion maps. PET provides 3D metabolic images that assist in tumor localization. The impact of the nuclear medicine images on the treatment planning process was assessed by determining the frequency, type, and extent of changes to plans. Pre-radiotherapy SPECT scans were used to modify 11 (11%) treatment plans; primarily altering beam angles to avoid highly functioning tissue. Fifty (48%) SPECT datasets were judged to be 'potentially useful' due to the detection of hypoperfused regions of the lungs, but were not used during treatment planning. PET data influenced 34% (12 of 35) of the treatment plans examined, and resulted in enlarging portions of the beam aperture (margins) up to 15 mm. Challenges associated with image quality and registration arise when utilizing nuclear medicine data in the treatment planning process. Initial implementation of advanced SPECT image reconstruction techniques that are not typically used in the clinic suggests that the reconstruction method may influence dose response data derived from the SPECT images and improve image registration with CT. The use of nuclear medicine transmission computed tomography (TCT) for both SPECT and PET is presented as a possible tool to reconstruct more accurate emission images and to aid in the registration of emission data with the planning CT. Nuclear medicine imaging techniques appear to be a potentially valuable tool during radiotherapy treatment planning for patients with lung cancer. The utilization of accurate nuclear medicine image reconstruction techniques and TCT may improve the treatment planning process.

Lung tumor growth correlates with glucose metabolism measured by fluoride-18 fluorodeoxyglucose positron emission tomography.

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.

Binding of [3H](+)-BW373U86 to delta-opioid receptors in rat brain membranes.

A tritiated form of the non-peptide delta-opioid receptor agonist (+)-BW373U86 ((+)-4-((alpha-R)-alpha-((2S,5R)-4-allyl-2, 5-dimethyl-l-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide) was synthesized and its binding characteristics studied. [3H](+)-BW373U86 bound with subnanomolar affinity to rat brain membranes and was displaced most effectively by ligands selective for delta-opioid receptors. Naltrindole, naltriben, and 7-benzylidenenaltrexone exhibited apparent inhibition constants of 0.06, 1.54, and 4.49 nM, respectively, while mu- or kappa-selective ligands showed little affinity for this site. [3H](+)-BW373U86 binding was sensitive to the presence of guanine nucleotides; GDP caused a 3-fold decrease and 5'-guanylyl-imidodiphosphate (Gpp[NH]p) caused a 25% increase in binding affinity.