Insights into lung cancer diagnosis and clinical management using [18F]F-fibroblast activation protein inhibitor (FAPI)-42 positron emission tomography/computed tomography (PET/CT).

Purpose: Accurate diagnosis and staging of lung cancer are critical for optimal clinical management. Fibroblast activation protein inhibitor (FAPI) imaging has emerged as a promising modality with superior detection capabilities for lung cancer. We hypothesized that [¹⁸F]FAPI-42 PET/CT would enhance diagnosis, TNM staging, and influence oncologic management in patients with suspected or confirmed lung cancer.

Methods: In this retrospective study, 155 patients with clinically suspected or confirmed lung cancer underwent both conventional imaging and [¹⁸F]FAPI-42 PET/CT scans within a one-week interval, without any intervening treatment. Lesions were visually assessed and categorized to evaluate the diagnostic capability of [¹⁸F]FAPI-42 PET/CT. Tracer activity was quantified using maximum standardized uptake values (SUV_max) and tumor-to-background ratios. TNM staging was independently determined by a board-certified radiologist or nuclear medicine physician using both imaging modalities, and discrepancies were assessed. Changes in TNM staging were documented and evaluated for their impact on clinical management.

Results: Of the 155 patients, 99 were evaluated for primary lesion diagnosis and staging. Pathological examination confirmed malignant tumors in 87 patients and benign tumors in 12. The diagnostic sensitivity and positive predictive value of [¹⁸F]FAPI-42 PET/CT for detecting primary lung tumors were 96.77% and 92.78%, respectively. Malignant lesions exhibited significantly higher SUV_max compared to benign lesions (5.2 vs. 1.5, P = 0.0002), with an area under the ROC curve of 0.87. In total, 1,556 malignant lesions were identified among patients with lung cancer, and [¹⁸F]FAPI-42 PET/CT demonstrated a diagnostic accuracy of 95.50%. However, its sensitivity for detecting adrenal metastases was lower at 33.33%, with a specificity of 100% and an accuracy of 53.85%. The use of [¹⁸F]FAPI-42 PET/CT resulted in changes in TNM staging for 46% of patients, leading to upstaging in 58 patients and downstaging in 5. These staging adjustments directly impacted clinical management in 34 patients, prompting modifications in treatment plans.

Conclusion: [¹⁸F]FAPI-42 PET/CT is a promising modality for lung cancer diagnosis and staging, demonstrating high sensitivity and specificity. Its use significantly altered TNM staging in nearly half of the patients, directly impacting oncologic management and treatment planning. However, its limited sensitivity for detecting adrenal metastases underscores the need for additional imaging techniques.