Supplementary Material for: Somatostatin Receptor Imaging in Mice with Difference Positive Rate of SSTR2

Introduction: Imaging with [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11 and [18F]AlF-NOTA-JR11 was performed to analyze differences among the three probes, and to analyze the correlation between the image and pathology parameters.
Method: Tumor bearing mice with different positive rates of somatostatin receptor II (SSTR2) were established with HEK293-SSTR2 and HEK293 cells, and imaging was performed on the same mouse with [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11 and [18F]AlF-NOTA-JR11 at 20, 60 and 120 min. The image parameters were obtained, including the maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), standard deviation of SUVmean (SD), tumor volume and coefficient of variation (CoV). Immunohistochemistry of the tumor was performed after imaging to obtain positive rate of SSTR2. Statistical analysis was performed to analyze the differences among the three imaging techniques and the correlations between the relative imaging parameter and immunohistochemistry (IHC).
Result: The SUVmax of [18F]AlF-NOTA-JR11 at 20 and 60 min was higher than that of [68Ga]Ga-DOTA-TATE (P=0.0015, 0.0035) and [68Ga]Ga-DOTA-JR11 (P=0.033, 0.019), and no significant difference was found in the other groups (P>0.05). There was a significant positive correlation between the positive rate and SUVmean of tumors with three tracers (P<0.05). However, a significant negative correlation between the positive rate and CoV was found only in the [68Ga]Ga-DOTA-TATE group at 60 min and 120 min (P=0.048, 0.026).
Conclusion: [18F]AlF-NOTA-JR11 is more suitable for SSTR imaging within an hour than other two tracers. SUVmean of whole tumor can become an indicator for evaluating the positive rate of IHC, and the higher SUVmean of three tracers means a higher positive rate. However, the CoV is not applicable to the two antagonist tracers for evaluating the positive rate.

引言：本研究采用[68Ga]Ga-DOTA-TATE、[68Ga]Ga-DOTA-JR11与[18F]AlF-NOTA-JR11三种探针开展成像实验，旨在分析三者间的性能差异，并探究影像参数与病理参数的相关性。
方法：通过HEK293-SSTR2与HEK293细胞构建生长抑素受体II（SSTR2）阳性率各异的荷瘤小鼠模型，于注射显像剂后20、60及120分钟，对同一小鼠依次使用三种探针进行成像。采集包括最大标准摄取值（SUVmax）、平均标准摄取值（SUVmean）、SUV均值标准差（SD）、肿瘤体积及变异系数（CoV）在内的多项影像参数。成像完成后对肿瘤组织实施免疫组化（IHC）检测，以获取SSTR2阳性率。通过统计学分析，比较三种成像技术的差异，并探究相对影像参数与免疫组化结果的相关性。
结果：[18F]AlF-NOTA-JR11在注射后20分钟与60分钟的最大标准摄取值（SUVmax）均高于[68Ga]Ga-DOTA-TATE（P=0.0015、0.0035）与[68Ga]Ga-DOTA-JR11（P=0.033、0.019），其余组别均无显著统计学差异（P>0.05）。三种显像剂对应的肿瘤平均标准摄取值（SUVmean）与SSTR2阳性率均呈显著正相关（P<0.05）。但仅在[68Ga]Ga-DOTA-TATE组中，注射后60分钟与120分钟时，肿瘤SSTR2阳性率与变异系数（CoV）呈显著负相关（P=0.048、0.026）。
结论：[18F]AlF-NOTA-JR11相较于其余两种显像剂，更适用于1小时内的生长抑素受体成像。全肿瘤平均标准摄取值可作为评估免疫组化阳性率的有效指标，三种显像剂的平均标准摄取值越高，对应的SSTR2阳性率也越高。但变异系数（CoV）不适用于另外两种拮抗剂类显像剂的阳性率评估。