[¹⁸F] AlF-NOTA-FAPI-04 PET/CT scans can predict pathologic complete response in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Abstract

We evaluated whether using the tracer [¹⁸F] AlF-NOTA-FAPI-04. in positron emission tomography/computed tomography (PET/CT) could predict pathologic complete response (pCR) rates in patients receiving neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). We prospectively evaluated 60 patients with histopathologically confirmed primary rectal cancer (20 referred for surgery and 40 for nCRT) who provided pretreatment [¹⁸F] AlF-NOTA-FAPI-04 PET/CT scans to detect FAP on tumor surfaces. Among those 40 patients, 26 provided a second [¹⁸F] AlF-NOTA-FAPI-04 PET/CT scan after the 10th radiotherapy fraction to assess changes in FAPI uptake variables. Correlations between baseline PET variables and markers of cancer-associated fibroblasts (CAFs) were assessed with Spearman's rank test. Relationships between pathologic remission and potential predictors were assessed with logistic regression. The FAPI PET variables maximum and mean standardized uptake values (SUVmax, SUVmean) were positive correlated with FAP expression (p < 0.05). Receiver operating characteristic curve analysis identified SUV_mean (area under the curve [AUC] = 0.869, p < 0.001; cutoff value 6.02; sensitivity 100%; specificity 74.2%) and SUV_max (AUC = 0.810, p = 0.005; cutoff value 11.46; sensitivity 77.8%; specificity 80.6%), both for the primary tumor, as predicting pCR. Multivariate logistic regression showed that SUV_mean was an independent predictor of good response (odds ratio = 0.295, 95% confidence interval [CI] 0.113-0.772, p = 0.013). Changes in FAPI uptake variables were not correlated with radiotherapy response. [¹⁸F] AlF-NOTA-FAPI-04 PET/CT uptake variables reflected the expression of CAF-related biomarkers. Higher baseline SUV_mean on [¹⁸F] AlF-NOTA-FAPI-04 PET/CT scans was associated with poor response to nCRT for LARC.