Qing Xie1, Teli Liu1, Jing Ding1, Nina Zhou1, Xiangxi Meng1, Hua Zhu1, Nan Li1, Jiangyuan Yu2, Zhi Yang3. 1. Department of Nuclear Medicine, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd., Beijing, 100142, China. 2. Department of Nuclear Medicine, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd., Beijing, 100142, China. yujiangyuan@aliyun.com. 3. Department of Nuclear Medicine, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd., Beijing, 100142, China. pekyz@163.com.
Abstract
PURPOSE: A [18F]AlF-labeled somatostatin receptor (SSTR) antagonist was developed for imaging of neuroendocrine neoplasms (NENs), evaluated and compared with [68Ga]Ga-DOTA-TATE. METHOD: [18F]AlF-NOTA-JR11 was synthesized manually and qualified with high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). The cellular uptake, internalization, and saturation binding were performed with HEK293-SSTR2 cells. Biodistribution and micro-PET imaging were carried out with HEK293-SSTR2 tumor-bearing mice. [18F]AlF-NOTA-JR11 PET/MR imaging and [68Ga]Ga-DOTA-TATE PET/CT were performed with ten patients of NEN at 50~60 min post-injection (p.i.). Normal organ biodistribution and tumor detectability were evaluated. RESULT: [18F]AlF-NOTA-JR11(24~36 GBq/μmol) was prepared within 30 min and 51.35 ± 3.30% (n > 10)of radiochemical yield. The radiochemical purity was 98.74 ± 1.24% (n > 10). Two stereoisomers were found and confirmed by LC-MS. The cellular uptake of [18F]AlF-NOTA-JR11 and [68Ga]Ga-DOTA-TATE were 4.50 ± 0.31 and 4.50 ± 0.13 %AD/105 cells at 30 min, and the internalization at 37 °C of [18F]AlF-NOTA-JR11 (5.47 ± 0.32% at 60 min) was significantly lower than [68Ga]Ga-DOTA-TATE (66.89 ± 1.62% at 60 min). The affinity of [18F]AlF-NOTA-JR11 (Kd = 11.59 ± 1.31 nM) was slightly lower than [68Ga]Ga-DOTA-TATE (Kd = 7.36 ± 1.02 nM); [18F]AlF-NOTA-JR11 showed high uptake in tumor (9.02 ± 0.92 %ID/g at 60 min p.i.) which can be blocked by 50 μg of NOTA-JR11 (3.40 ± 1.64 %ID/g at 60 min p.i.); the result was coincident with micro-PET imaging. Imaging study of NEN patients showed that more lesions were found only by [18F]AlF-NOTA-JR11 (n = 67 vs. 1 only by [68Ga]Ga-DOTA-TATE), and the uptakes of [18F]AlF-NOTA-JR11 in majority normal organs were significantly lower than [68Ga]Ga-DOTA-TATE. The target to nontarget of maximum of standard uptake value (SUVmax) of [18F]AlF-NOTA-JR11 in liver lesions were significantly higher than those of [68Ga]Ga-DOTA-TATE. CONCLUSION: Qualitied [18F]AlF-NOTA-JR11 is prepared conveniently with reasonable yield, and it can bind SSTR2 specifically with high affinity. Excellent imaging capability of [18F]AlF-NOTA-JR11 for NENs is superior to [68Ga]Ga-DOTA-TATE, especially in digestive system. It has a great potential for imaging of NENs.
PURPOSE: A [18F]AlF-labeled somatostatin receptor (SSTR) antagonist was developed for imaging of neuroendocrine neoplasms (NENs), evaluated and compared with [68Ga]Ga-DOTA-TATE. METHOD: [18F]AlF-NOTA-JR11 was synthesized manually and qualified with high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). The cellular uptake, internalization, and saturation binding were performed with HEK293-SSTR2 cells. Biodistribution and micro-PET imaging were carried out with HEK293-SSTR2tumor-bearing mice. [18F]AlF-NOTA-JR11 PET/MR imaging and [68Ga]Ga-DOTA-TATE PET/CT were performed with ten patients of NEN at 50~60 min post-injection (p.i.). Normal organ biodistribution and tumor detectability were evaluated. RESULT: [18F]AlF-NOTA-JR11(24~36 GBq/μmol) was prepared within 30 min and 51.35 ± 3.30% (n > 10)of radiochemical yield. The radiochemical purity was 98.74 ± 1.24% (n > 10). Two stereoisomers were found and confirmed by LC-MS. The cellular uptake of [18F]AlF-NOTA-JR11 and [68Ga]Ga-DOTA-TATE were 4.50 ± 0.31 and 4.50 ± 0.13 %AD/105 cells at 30 min, and the internalization at 37 °C of [18F]AlF-NOTA-JR11 (5.47 ± 0.32% at 60 min) was significantly lower than [68Ga]Ga-DOTA-TATE (66.89 ± 1.62% at 60 min). The affinity of [18F]AlF-NOTA-JR11 (Kd = 11.59 ± 1.31 nM) was slightly lower than [68Ga]Ga-DOTA-TATE (Kd = 7.36 ± 1.02 nM); [18F]AlF-NOTA-JR11 showed high uptake in tumor (9.02 ± 0.92 %ID/g at 60 min p.i.) which can be blocked by 50 μg of NOTA-JR11 (3.40 ± 1.64 %ID/g at 60 min p.i.); the result was coincident with micro-PET imaging. Imaging study of NEN patients showed that more lesions were found only by [18F]AlF-NOTA-JR11 (n = 67 vs. 1 only by [68Ga]Ga-DOTA-TATE), and the uptakes of [18F]AlF-NOTA-JR11 in majority normal organs were significantly lower than [68Ga]Ga-DOTA-TATE. The target to nontarget of maximum of standard uptake value (SUVmax) of [18F]AlF-NOTA-JR11 in liver lesions were significantly higher than those of [68Ga]Ga-DOTA-TATE. CONCLUSION: Qualitied [18F]AlF-NOTA-JR11 is prepared conveniently with reasonable yield, and it can bind SSTR2 specifically with high affinity. Excellent imaging capability of [18F]AlF-NOTA-JR11 for NENs is superior to [68Ga]Ga-DOTA-TATE, especially in digestive system. It has a great potential for imaging of NENs.
Entities:
Keywords:
AlF; Antagonist; Neuroendocrine neoplasms; PET imaging;; Somatostatin receptor
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