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

doi:10.2967/jnumed.124.267529

Granzyme B PET/CT Imaging Evaluates Early Response to Immunotherapy in Gastric Cancer

J Nucl Med. 2024 Oct 10:jnumed.124.267529. doi: 10.2967/jnumed.124.267529. Online ahead of print.

Authors

Qiufang Liu^{1

2

3

4}, Xiaoping Xu^{1

2

3

4}, Ziyi Yang^{1

2

3

4}, Jianping Zhang^{1

2

3

4}, Jindian Li^{1

2

3

4}, Ying Qiao^{1

2

3

4}, Silong Hu^{1

2

3

4}, Xiaosheng Liu^{1

2

3

4}, Weijian Guo^{5

6}, Shaoli Song^{7

2

3

4}

Affiliations

¹ Department of Nuclear Medicine, Shanghai Cancer Center, Fudan University, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China.
⁴ Key Laboratory of Nuclear Physics and Ion-Beam Application, MOE, Fudan University, Shanghai, China; and.
⁵ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; shaoli-song@163.com guoweijian1@sohu.com.
⁶ Department of Gastrointestinal Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China.
⁷ Department of Nuclear Medicine, Shanghai Cancer Center, Fudan University, Shanghai, China; shaoli-song@163.com guoweijian1@sohu.com.

PMID: 39389628
DOI: 10.2967/jnumed.124.267529

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-DOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUV_max of primary tumors (SUV_max-t), SUV_max of metastatic lymph nodes (SUV_max-LN), and SUV_max 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_tumor and TBR_tumor and for metastatic lymph nodes as TLR_LN and TBR_LN, 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-DOTA-GSI PET/CT parameters in identifying responders. Two-tailed P value of less than 0.05 was considered statistically significant. Results: We found that SUV_max-t, TLR_tumor, TBR_tumor, SUV_max-LN, and TBR_LN 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 SUV_max-t, TBR_tumor, TLR_tumor, SUV_max-LN, TLR_LN, and TBR_LN was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUV_max-t was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBR_tumor was an independent predictor of treatment response (P = 0.03). Conclusion: Our results indicated that [⁶⁸Ga]Ga-DOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.

Keywords: PET/CT; gastric cancer; granzyme B; immunotherapy; response prediction.