The role of fluorodeoxyglucose positron emission tomography

Authors

Abstract

AimLung cancer is one of the leading causes of cancer-related deaths worldwide. Timely diagnosis of lesions detected on radiological imaging is critical for appropriate treatment planning. In our study, we evaluated the diagnostic performance of FDG PET-CT in lung lesions.
MethodsThe study included 213 patients who had lesions larger than 1 cm detected on lung tomography and who underwent diagnostic PET-CT scans. Patients who underwent biopsy after PET-CT or who had radiological follow-up for 2 years were included in the study. Patient files were retrospectively reviewed.
ResultsOf the 213 patients participating in the study, 162 (76%) were diagnosed with malignant disease and 51 (24%) were diagnosed with benign disease. Advanced age (p=0.02) and smoking (p=0.001) were significantly more prevalent in the malignant group. In our study cohort, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG PET-CT were 100%, 49%, 86%, and 100%, respectively.
ConclusionAlthough PET-CT sensitivity was high in our study, its specificity was lower than that reported in meta-analyses. The most important factor contributing to this situation is false positives. Pathologies such as granulomatous-inflammatory diseases generally constituted the false positive group in our study. Due to their high prevalence, it should be kept in mind that such pathologies may be included in the differential diagnosis of hypermetabolic lesions detected on diagnostic FDG PET-CT.

Keywords

Introduction

Pulmonary nodules and masses are increasingly detected in clinical practice owing to the widespread use of high-resolution computed tomography (CT) and lung cancer screening programs. While a pulmonary nodule is defined as a lesion ≤3 cm in diameter, lesions exceeding 3 cm are categorized as pulmonary masses and carry a substantially higher probability of malignancy. Given that lung cancer remains the leading cause of cancer-related mortality worldwide, accurate characterization of these lesions is critical for timely diagnosis and appropriate therapeutic planning.^1,2
Although CT provides detailed morphological assessment, imaging features alone are often insufficient to reliably distinguish benign from malignant lesions, particularly in indeterminate nodules and metabolically heterogeneous masses. Fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) addresses this limitation by integrating metabolic and anatomical information in a single examination. Malignant cells typically demonstrate increased glucose utilization, resulting in elevated FDG uptake that can be quantitatively assessed using standardized uptake values (SUV), most commonly Maximum Standardized Uptake Value (SUVmax).³
Accumulating evidence indicates that integrated FDG PET-CT improves diagnostic confidence in the evaluation of pulmonary nodules and masses by refining malignancy risk stratification and enhancing clinical decision-making.^4,5,6 Its ability to provide whole-body staging information, in addition to lesion characterization, supports appropriate therapeutic planning and may reduce unnecessary invasive procedures. Current evidence-based guidelines therefore recommend FDG PET-CT for indeterminate pulmonary nodules larger than 8 mm and for the preoperative assessment of suspected malignant masses.^2,7
Despite its established clinical role, FDG PET-CT has recognized limitations, including false-positive findings in inflammatory or granulomatous conditions and reduced sensitivity in small or low-metabolic tumors.⁵
In this study, we evaluated the diagnostic performance of FDG PET-CT for pulmonary nodules and masses, analyzed false-positive and false-negative pathologies, and assessed the effect of dual-phase imaging on overall diagnostic accuracy.

Materials and Methods

This study included 213 patients with lung lesions larger than 1 cm who underwent diagnostic FDG PET-CT scans at the Department of Nuclear Medicine, XXX University, between January 2010 and December 2012. The histopathological results of patients who underwent biopsy after the scan, and the images and imaging reports of patients who were radiologically followed for a minimum of two years were retrospectively reviewed.
Inclusion Criteria for the Study• Patients who had undergone a chest CT scan within the recent period (upper limit of one month) and had solitary or multiple lesions larger than 1 cm detected in the lungs
• Patients who received a histopathological diagnosis or those who were followed for a minimum of two years radiological follow-up after a diagnostic PET-CT scan were included in the study.
Exclusion Criteria for the Study• Patients with a histopathological diagnosis before the PET-CT scan
• Patients with a known history of malignancy
• Patients who did not receive a histopathological diagnosis or were not followed radiologically after the PET-CT scan
• Patients with fasting blood glucose levels exceeding 200 mg/dL on the day of the study were excluded.
Imaging ProtocolImaging was performed with a Siemens Biograph 2 PET-CT scanner. Patients were injected intravenously with 0.15–0.20 mCi/kg of F18-FDG . One hour after injection, imaging was completed in an average of 7–8 bed positions. For lesions that were borderline with respect to the malignant-benign distinction, images from the second hour (dual-phase study) were taken of the suspicious area.
Lesions with an SUVmax> 2.5 were classified as malignant.
This article was prepared based on the doctoral dissertation entitled “The Role of FDG-PET-CT in the Diagnosis of Pulmonary Lesions Larger Than 1 cm”
Ethical ApprovalThe study was approved by the Ethics Committee of Gaziantep University (Date: 14.05.2013, Decision No: 182).
Statistical AnalysisThe Kolmogorov-Smirnov test, Student's t-test, Mann-Whitney U test, Kruskal-Wallis test, and Dunn's multiple-comparison test were used in the study. The relationship between categorical variables was tested using chi-square analysis. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated. The diagnostic performance of continuous variables was assessed using ROC curve analysis. SPSS for Windows version 11.5 was used for statistical analyses, and p<0.05 was considered statistically significant.
Reporting GuidelinesThis study was reported in accordance with the STROBE guideline.

Results

The study included 213 patients who underwent diagnostic PET-CT scans between 2010 and 2012. Of the patients who presented, 202 received a pathological diagnosis, while 11 were followed up radiologically. Among patients under radiological follow-up, lesions that regressed after nonspecific treatment or remained stable during radiological follow-up within 2 years were considered benign.
Among the patients in the study, 182 (85%) were male and 31 (15%) were female . The patients' ages ranged from 18 to 80. 51% of women had a malignant diagnosis, compared with 80% of men. The mean age of patients with a malignant diagnosis was 60.6±10.7, while the mean age of those with a benign diagnosis was 54.1±13.4; the mean age of patients with a malignant diagnosis was higher than that of patients with a benign diagnosis (p=0.02).
Of the 213 patients, 170 (80%) had a history of smoking. Of the 170 patients who smoked, 142 had malignant pathology (83%) and 28 had benign pathology (17%). Among the 43 patients with no history of smoking, 20 had malignant pathology (48%) and 23 had benign pathology (52%). There was a significant association between smoking and malignancy in the study group (p=0.001).
The sizes of the lesions detected on the chest CT scans performed before the FDG PET-CT examination in the study patients ranged from 10 to 130 mm. In four patients, the size of the mass could not be measured because it could not be distinguished from the area of collapse and consolidation on the CT scan. Among lesions up to 3 cm in diameter, 33 (56%) were malignant and 27 (44%) were benign . Of the lesions larger than 3 cm, 125 (83%) were malignant and 24 (17%) were benign. In addition, the pathology results of four patients whose lesion size could not be measured due to collapse-consolidation were malignant.. The malignancy rate in mass lesions larger than 3 cm was higher than that in lesions smaller than 3 cm, and this difference was statistically significant(p:0.001).
The SUVmax value of lesions smaller than 3 cm ranged from 0.6 to 23.7, with a mean SUVmax value of 6.3±5.1. The SUVmax values of lesions larger than 3 cm ranged from 0.5 to 37, with a mean SUVmax value of 13.2±7.2. The mean SUVmax of mass lesions larger than 3 cm was significantly higher than that of nodular lesions smaller than 3 cm (p=0.001). In addition, a moderate positive correlation was observed between lesion size and SUVmax value (r=0.515, p=0.001).
Of the 213 patients participating in the study, 162 (76%) were diagnosed as malignant and 51 (24%) as benign. In malignant cases, the SUVmax value ranged from 2.9 to 37, with a mean SUVmax value of 13.4±6.8. In benign cases, the SUVmax value ranged from 0.5 to 16.8, with a mean SUVmax value of 4.5±4.4. The mean SUVmax value in malignant cases was significantly higher than that in benign cases (p=0.001).
The pathological diagnoses of patients with malignancies are listed in Table 1.
Fifty-one patients in the study had been diagnosed with benign pathology. Eleven of these patients were considered to have benign findings based on radiological follow-up. The SUVmax values of the lesions in the lungs of these 11 patients, followed up radiologically, were <2,5, and the mean SUVmax value was 1.4±0.5. Forty patients had a histopathological diagnosis of benign disease after surgery. Twenty-six of the 40 patients with a histopathological diagnosis of benign disease had an SUVmax value >2,5. The mean SUVmax value for these 26 patients was 7.5±4.4. The numbers and diagnoses of patients considered benign are shown in Table 2.
In our study, SUVmax was used to differentiate benign from malignant nodule-mass lesions detected in the lungs by PET-CT. When an SUVmax value > 2.5 was considered malignant, the sensitivity, specificity, PPV, and NPV of PET-CT were 100%, 49%, 86.1%, and 100%, respectively.
In the ROC analysis, the SUVmax value was 7.1 for optimal sensitivity and specificity, with sensitivity and specificity of 87.7% and 80%, respectively (AUC: 0.887; 95% confidence interval).
Twenty-five patients in the study underwent dual-phase imaging. Three patients who underwent dual-phase imaging had SUVmax<2.5 in the first hour, and their SUVmax values decreased in the second hour. These three patients were assessed as benign based on radiological follow-up. In 22 patients, the first-hour SUVmax value was >2.5, and in all of these patients the second-hour SUVmax value increased. All patients received a histopathological diagnosis, with 12 receiving a malignant diagnosis (55%) and 10 receiving a benign diagnosis (45%). The mean SUVmax increase in malignant cases was %27.97±19.69, while the SUVmax increase in benign cases was %26.44±15.8, and there was no significant difference in SUVmax increase percentages when the two groups were compared (p=0.844).
Images from one of our cases are shown below (Figure 1).

Discussion

In our study, the majority of patients were male, and malignancy was significantly more frequent in men than in women. Additionally, patients with malignant lesions were significantly older than those with benign lesions, and a history of smoking was strongly associated with malignancy. Risk factors for lung cancer, such as smoking and advanced age, and the higher incidence of lung cancer in men, are consistent with extensive meta-analyses and studies on this subject.^8,9,10
In our study, the malignancy rate in masses larger than 3 cm was significantly higher than that in nodules smaller than 3 cm. Furthermore, the mean SUVmax value in malignant cases was significantly higher than in benign pathologies. A meta-analysis and a prospective multicentre trial have shown that SUVmax values are significantly higher in malignant cases than in benign cases, and that the rate of malignancy increases with lesion diameter.^11,12 Our study is consistent with the literature in this respect.
Our research group included both mass lesions and nodules. In our study, SUVmax was used to differentiate benign from malignant lesions. When an SUVmax value >2.5 was considered malignant, PET-CT sensitivity, specificity, PPV, and NPV were 100%, 49%, 86.1%, and 100%, respectively. In a meta-analysis by Li et al. including 1557 patients, the pooled sensitivity and specificity of FDG PET-CT for pulmonary lesions were reported as 89% and 70%, respectively.¹³ Similarly, Ruilong et al., in a separate meta-analysis comprising 1297 patients, reported a sensitivity of 82% and a specificity of 81%.¹⁴ Compared with these pooled estimates, the sensitivity observed in our study was higher, whereas the specificity was lower.The low specificity rate was thought to be due to false-positive results among patients in our group.
In the ROC analysis , the SUVmax cutoff value for optimal sensitivity and specificity in our study group was calculated to be 7.1, which is significantly higher than the commonly accepted value of 2.5. Weir-McCall et al. emphasized in their study that SUVmax thresholds should be adjusted according to lesion size; for example, they recommended an SUVmax value of ≥3.6 for nodules >16 mm.¹² The cutoff value in our study is higher and can be explained by the higher SUVmax values observed in masses larger than 3 cm.
Although FDG PET has high diagnostic value, some situations lead to false positives and false negatives. In our study, false positives were detected in 26 patients (12.2%). The most common pathologies in our false-positive patient group were chronic and granulomatous inflammation. In inflammatory and granulomatous diseases, activated macrophages and inflammatory cells exhibit increased glucose metabolism, leading to false-positive FDG uptake. Meta-analyses conducted similarly to our group's findings indicate that chronic inflammation and granulomatous inflammation are significant causes of false positives.^5,13 Deppen et al. showed that in regions with endemic infectious lung disease, pooled specificity may fall to nearly 60% due to granulomatous processes mimicking malignancy.⁵
Efforts continue to improve the accuracy of the method by reducing false-negative and false-positive PET findings. One of these studies is dual-phase imaging. In our study, we performed dual-phase imaging in 25 patients to improve accuracy. The mean SUVmax increase at the second hour was 27.97±19.69% in the malignant group and 26.44±15.82% in the benign group, with no significant difference in SUVmax increase percentages between the two groups. A meta-analysis involving 816 patients indicated that single-phase and dual-phase imaging showed similar sensitivity and specificity in the diagnosis of pulmonary nodules.¹⁵ Another meta-analysis of 415 patients reported that dual-phase imaging had similar accuracy to single-phase imaging in the differential diagnosis of pulmonary nodules but was more specific.¹⁶ The findings reported in these two meta-analyses are consistent with the results obtained in our study.

Limitations

The retrospective single-center design and the lack of histopathological confirmation in all patients may limit the generalizability of the findings.

Conclusion

Numerous contemporary studies have established FDG PET-CT as a validated imaging modality for the diagnosis, staging, assessment of treatment response, radiotherapy planning, and restaging of lung cancer. In our study, we investigated the diagnostic role of PET-CT in the evaluation of nodular and mass lesions detected in the lungs. Although sensitivity was high, specificity remained below the average reported in the meta-analyses. The most significant factor in this situation is false positive cases. Granulomatous diseases, such as sarcoidosis and tuberculosis, and zoonotic infections are common in our country; in our study, these pathologies generally constituted the false-positive group, thereby reducing specificity. Because of their high prevalence, these benign pathologies should also be considered in the differential diagnosis of hypermetabolic lesions on FDG PET-CT scans performed for diagnostic purposes. In conclusion, although some pathologies may lead to false positives, diagnostic PET-CT for lung nodules and masses plays an important role in demonstrating the metabolic status of lesions and guiding patient management.

Declarations

Abbreviations

AUC: Area under the curve
CT: Computed tomography
FDG: Fluorodeoxyglucose
NPV: Negative predictive value
PET-CT: Positron emission tomography–computed tomography
PPV: Positive predictive value
ROC: Receiver operating characteristic
SPSS: Statistical package for the social sciences
SUV: Standardized uptake value
SUVmax: Maximum standardized uptake value

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About This Article

Received:

May 21, 2026

Published Online:

June 21, 2026