{"title":"Granzyme B PET/CT Imaging Evaluates Early Response to Immunotherapy in Gastric Cancer.","authors":"Qiufang Liu, Xiaoping Xu, Ziyi Yang, Jianping Zhang, Jindian Li, Ying Qiao, Silong Hu, Xiaosheng Liu, Weijian Guo, Shaoli Song","doi":"10.2967/jnumed.124.267529","DOIUrl":null,"url":null,"abstract":"<p><p>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-NOTA-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-NOTA-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-NOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2967/jnumed.124.267529","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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, [68Ga]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. Methods: Seventy-two patients with gastric cancer (stages III-IV) were recruited for [68Ga]Ga-NOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUVmax of primary tumors (SUVmax-t), SUVmax of metastatic lymph nodes (SUVmax-LN), and SUVmax 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 TLRtumor and TBRtumor and for metastatic lymph nodes as TLRLN and TBRLN, 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 [68Ga]Ga-NOTA-GSI PET/CT parameters in identifying responders. Two-tailed P value of less than 0.05 was considered statistically significant. Results: We found that SUVmax-t, TLRtumor, TBRtumor, SUVmax-LN, and TBRLN were higher in responders than in nonresponders (2.49 ± 0.58 vs. 1.55 ± 0.48, P = 0.000; 2.24 ± 0.48 vs. 1.74 ± 0.67, P = 0.007; 1.38 ± 0.43 vs. 0.90 ± 0.23, P = 0.000; 2.24 ± 0.99 vs. 1.42 ± 0.55, P = 0.003; and 1.28 ± 0.68 vs. 0.83 ± 0.32, P = 0.012, respectively). According to receiver operating characteristic curve analysis, the area under the curve for SUVmax-t, TBRtumor, TLRtumor, SUVmax-LN, TLRLN, and TBRLN was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUVmax-t was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBRtumor was an independent predictor of treatment response (P = 0.03). Conclusion: Our results indicated that [68Ga]Ga-NOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.