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Somatostatin Receptor Imaging in Mice with Difference Positive Rate of SSTR2
Qing Xie1, Wenyuan Zhou1, Xiangxi Meng1
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancer, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China.
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, tumor volume, and coefficient of variation (CoV). Immunohistochemistry (IHC) 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 IHC.
Result:
The SUVmax of [18F]AlF-NOTA-JR11 at 20 min 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.
Insights
[18F]AlF-NOTA-JR11 is optimal for somatostatin receptor imaging within 60 minutes. Mean standard uptake value (SUVmean) correlates with SSTR2 positivity, but coefficient of variation (CoV) is not suitable for antagonist tracers.
Area of Science:
- Nuclear medicine
- Radiopharmaceutical imaging
- Molecular imaging
Background:
- Somatostatin receptor II (SSTR2) imaging is crucial for diagnosing and monitoring neuroendocrine tumors.
- Development of novel radiotracers is essential for improving imaging sensitivity and specificity.
- Comparing the performance of different SSTR2-targeting probes is necessary for clinical application.
Purpose of the Study:
- To compare the imaging performance of three SSTR2-targeting probes: [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11, and [18F]AlF-NOTA-JR11.
- To evaluate the correlation between imaging parameters and SSTR2 expression levels determined by immunohistochemistry (IHC).
Main Methods:
- Tumor-bearing mice with varying SSTR2 expression were injected with the three radiotracers.
- PET imaging was performed at 20, 60, and 120 minutes post-injection.
- Image parameters (SUVmax, SUVmean, CoV) and SSTR2 positive rates (IHC) were analyzed.
Main Results:
- [18F]AlF-NOTA-JR11 showed significantly higher SUVmax at 20 and 60 minutes compared to the other tracers.
- A significant positive correlation was observed between SUVmean and SSTR2 positive rate for all three tracers.
- A significant negative correlation between CoV and SSTR2 positive rate was found only for [68Ga]Ga-DOTA-TATE at later time points.
Conclusions:
- [18F]AlF-NOTA-JR11 is a promising SSTR2 imaging agent, particularly effective within the first hour.
- Tumor SUVmean derived from these tracers can serve as a reliable indicator of SSTR2 expression levels.
- CoV is not a suitable parameter for evaluating SSTR2 positive rates with antagonist tracers like [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-JR11.
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