Predictive Value of Intratumoral-metabolic Heterogeneity Derived from F-FDG PET/CT in Distinguishing Microsatellite Instability Status of Colorectal Carcinoma

Purpose/background: Microsatellite instability (MSI) status is a significant biomarker for the response to immune checkpoint inhibitors, response to 5-fluorouracil-based adjuvant chemotherapy, and prognosis in colorectal carcinoma (CRC). This study investigated the predictive value of intratumoral-metabolic heterogeneity (IMH) and conventional metabolic parameters derived from F-FDG PET/CT for MSI in patients with stage I-III CRC.

Methods: This study was a retrospective analysis of 152 CRC patients with pathologically proven MSI who underwent F-FDG PET/CT examination from January 2016 to May 2022. Intratumoral-metabolic heterogeneity (including heterogeneity index [HI] and heterogeneity factor [HF]) and conventional metabolic parameters (standardized uptake value [SUV], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) of the primary lesions were determined. MTV and SUV were calculated on the basis of the percentage threshold of SUVs at 30%-70%. TLG, HI, and HF were obtained on the basis of the above corresponding thresholds. MSI was determined by immunohistochemical evaluation. Differences in clinicopathologic and various metabolic parameters between MSI-High (MSI-H) and microsatellite stability (MSS) groups were assessed. Potential risk factors for MSI were assessed by logistic regression analyses and used for construction of the mathematical model. Area under the curve (AUC) were used to evaluate the predictive ability of factors for MSI.

Results: This study included 88 patients with CRC in stages I-III, including 19 (21.6%) patients with MSI-H and 69 (78.4%) patients with MSS. Poor differentiation, mucinous component, and various metabolic parameters including MTV, MTV, MTV, and MTV, as well as HI, HI, HI, and HF in the MSI-H group were significantly higher than those in the MSS group (all < 0.05). In multivariate logistic regression analyses, post-standardized HI by Z-score ( = 0.037, OR: 2.107) and mucinous component ( < 0.001, OR:11.394) were independently correlated with MSI. AUC of HI and our model of the HI + mucinous component was 0.685 and 0.850, respectively ( = 0.019), and the AUC of HI in predicting the mucinous component was 0.663.

Conclusions: Intratumoral-metabolic heterogeneity derived from F-FDG PET/CT was higher in MSI-H CRC and predicted MSI in stage I-III CRC patients preoperatively. HI and mucinous component were independent risk factors for MSI. These findings provide new methods to predict the MSI and mucinous component for patients with CRC.