Granzyme B PET/CT Imaging Evaluates Early Response to Immunotherapy in Gastric Cancer
Qiufang Liu, Xiaoping Xu, Ziyi Yang, Jianping Zhang, Jindian Li, Ying Qiao, Silong Hu, Xiaosheng Liu, Weijian Guo, Shaoli Song
Abstract
In several malignancies, only a limited number of patients respond to immune checkpoint inhibitors. Predicting and monitoring responses to these inhibitors represent an unmet clinical need. Here, we developed a PET/CT probe targeting granzyme B, [<sup>68</sup>Ga]Ga-NOTA-Gly-Gly-Gly-Ile-Glu-Pro-Asp-CHO (GSI), and aimed to investigate whether it can be used to monitor the effects of immune checkpoint inhibitors early in the course of therapy. <b>Methods:</b> Seventy-two patients with gastric cancer (stages III–IV) were recruited for [<sup>68</sup>Ga]Ga-DOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUV<sub>max</sub> of primary tumors (SUV<sub>max-t</sub>), SUV<sub>max</sub> of metastatic lymph nodes (SUV<sub>max-LN</sub>), and SUV<sub>max</sub> of normal tissues (liver and blood pool) were measured, and their target-to-liver background ratio (TLR) and target-to-blood background ratio (TBR) were denoted for primary tumors as TLR<sub>tumor</sub> and TBR<sub>tumor</sub> and for metastatic lymph nodes as TLR<sub>LN</sub> and TBR<sub>LN</sub>, respectively. The treatment responses were assessed within 1 wk after full-course treatment according to RECIST version 1.1. Wilcoxon rank-sum tests were used to compare the PET/CT parameters between responders and nonresponders. Receiver operating characteristic curve analysis was used to assess the diagnostic efficacy of [<sup>68</sup>Ga]Ga-DOTA-GSI PET/CT parameters in identifying responders. Two-tailed <i>P</i> value of less than 0.05 was considered statistically significant. <b>Results:</b> We found that SUV<sub>max-t</sub>, TLR<sub>tumor</sub>, TBR<sub>tumor</sub>, SUV<sub>max-LN</sub>, and TBR<sub>LN</sub> were higher in responders than in nonresponders (2.49 ± 0.58 vs. 1.55 ± 0.48, <i>P</i> = 0.000; 2.24 ± 0.48 vs. 1.74 ± 0.67, <i>P</i> = 0.007; 1.38 ± 0.43 vs. 0.90 ± 0.23, <i>P</i> = 0.000; 2.24 ± 0.99 vs. 1.42 ± 0.55, <i>P</i> = 0.003; and 1.28 ± 0.68 vs. 0.83 ± 0.32, <i>P</i> = 0.012, respectively). According to receiver operating characteristic curve analysis, the area under the curve for SUV<sub>max-t</sub>, TBR<sub>tumor</sub>, TLR<sub>tumor</sub>, SUV<sub>max-LN</sub>, TLR<sub>LN</sub>, and TBR<sub>LN</sub> was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUV<sub>max-t</sub> was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBR<sub>tumor</sub> was an independent predictor of treatment response (<i>P</i> = 0.03). <b>Conclusion:</b> Our results indicated that [<sup>68</sup>Ga]Ga-DOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.