Clinical Impact of FDG PET/CT in Pulmonary Nodule Characterization: Current Perspectives on Dual-Time-Point Imaging and Semi-Quantitative Imaging Metrics

<b>Background/Objectives:</b> Pulmonary nodules (PNs) are a common incidental finding on conventional imaging. Differentiating benign from malignant lesions remains a diagnostic challenge. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has become an essential imaging modality in this setting. This review aims to evaluate the clinical impact of PET/CT parameters and techniques, focusing on semi-quantitative imaging biomarkers and dual-time-point imaging. <b>Methods:</b> This review is organized into three main sections. First, qualitative analysis and PET key metrics are analyzed, including standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) indices, highlighting their diagnostic and prognostic significance. The second section focuses on the clinical utility of dual-time-point imaging (DTPI), evaluating its ability to differentiate between benign and malignant PNs through changes in SUV over time (ΔSUVmax). We compare these advanced imaging approaches with histopathological diagnosis, the current gold-standard method, highlighting the potential of advanced PET/CT techniques in clinical decision-making. The last section focuses on future applications of PET/MR, artificial intelligence, and PET radiomics. <b>Results:</b> Evidence indicates that high SUV, MTV, and TLG values are significantly associated with malignant PNs and aggressiveness. Moreover, DTPI with ΔSUV, ΔMTV, and ΔTLG further enhances specificity and accuracy in characterizing PNs. Despite a lack of standardization, studies have shown better accuracy when advanced PET/CT parameters are used. <b>Conclusions:</b> While DTPI and semi-quantitative PET parameters are not yet universally adopted in daily clinical practice, evidence supports their role in enhancing the characterization of indeterminate PNs. More prospective studies are needed.