Detecting pathological response to neoadjuvant therapy in rectal cancer by [18F]-FDG and [18F]-FAPI-42 PET/MRI

Accurate preoperative assessment of pathological response to neoadjuvant therapy (NAT) in rectal cancer remains challenging, particularly after immunotherapy. This study aimed to explore the feasibility of using post-treatment [ 18 F]-FDG and [ 18 F]-FAPI-42 PET/MRI to detect pathological response. Thirty-six patients with locally advanced rectal cancer who completed short-course radiotherapy followed by immunochemotherapy were prospectively enrolled. After 28 days, paired PET/MRI and dynamic contrast-enhanced MRI were performed, followed by surgery within one week. Combined PET/MRI interpretation achieved significantly higher accuracy for predicting tumor regression grade (TRG) (75.00%) and pathological complete response (pCR) (86.11%) than PET or MRI alone (all P < 0.05), with substantial agreement with pathology (κ = 0.66 for TRG; κ = 0.68 for pCR). [ 18 F]-FAPI-42 PET provided more parameters differentiating TRG groups than [ 18 F]-FDG PET. The FAPI-SUVmax/FDG-SUVmax ratio differed significantly between pCR and non-pCR groups ( P = 0.004) and showed good diagnostic performance for pCR (AUC = 0.82); a cutoff of 1.25 yielded 65% sensitivity and 92% specificity. Among MRI parameters, the time-intensity curve (TIC) outperformed ADC in predicting pCR (AUC 0.84 vs. 0.38). Post-treatment [ 18 F]-FDG and [ 18 F]-FAPI-42 PET/MRI effectively evaluate pathological response to NAT in rectal cancer. The FAPI-SUVmax/FDG-SUVmax ratio is a promising imaging biomarker for identifying pCR, potentially guiding surgery de-escalation. NCT06318234. https://clinicaltrials.gov/study/NCT06318234 .