Abstract
<jats:p> <jats:bold>Background:</jats:bold> In clinical positron emission tomography (PET), reliable scanner performance is essential to ensure accurate quantification and diagnostic confidence. While conventional PET systems are sensitive to defective detector blocks (DDBs), the tolerance limits for long axial field-of-view (LAFOV) PET systems, which feature a substantially higher number of detector elements and increased sensitivity, remain unclear. This study systematically evaluated the robustness of a LAFOV PET/CT system to DDBs to inform clinical quality control (QC) thresholds. <jats:bold>Methods:</jats:bold> The robustness of a LAFOV PET/CT system consisting of 1,216 detector blocks was evaluated using a clinical patient dataset and Monte Carlo-based phantom simulations. Various DDB configurations with different numbers and spatial distributions, including sparse and clustered patterns, were simulated by selectively removing coincidence events from list-mode data. Quantification biases were evaluated across phantom volumes-of-interest and 152 segmented patient lesions using SUV <jats:sub>mean</jats:sub> , SUV <jats:sub>peak</jats:sub> and SUV <jats:sub>max</jats:sub> under different reconstruction settings and acquisition durations. <jats:bold>Results:</jats:bold> Sparse DDBs resulted in limited and spatially diffuse biases, with SUV accuracy remaining within ±5% for up to eight DDBs under standard reconstruction settings and a 5-minute acquisition. Reconstruction using larger voxel sizes and image filtering, combined with a prolonged 10-minute acquisition, increased the tolerance up to 32 DDBs. In contrast, clustered defects induced pronounced localized biases, limiting tolerable conditions to four adjacent DDBs. SUV <jats:sub>max</jats:sub> showed the highest sensitivity to DDB-related effects. Increased biases were observed under low-count conditions, indicating reduced tolerance for low-dose PET applications. <jats:bold>Conclusions:</jats:bold> Quantification performance in LAFOV PET is primarily determined by the spatial distribution followed by the number of defective detector blocks. These findings support a re-evaluation of current QC criteria, incorporating defect configuration and acquisition conditions, to maintain quantitative reliability while extending system uptime. </jats:p>