1.Development and characterization of 18F-SQKJ-2: a novel PET tracer for the diagnosis of fear memory disorders
Wanli HE ; Chenxin MA ; Xinghai CAO ; Junwei CHEN ; Yan GU ; Shuxia CAO ; Zhiqiang WANG ; Dilong MAO ; Qinggang HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(11):672-677
Objective:To develop and validate a novel PET tracer, N-cyclohexyl-4-((2, 4-dichlorophenyl)(4-(fluoro- 18F)phenyl)methyl)piperazine-1-carboxamide ( 18F-SQKJ-2), targeting cannabinoid type 1 (CB1) receptors for diagnosing psychiatric disorders associated with fear memory. Methods:18F-SQKJ-2 was prepared using a nucleophilic substitution radiochemical synthesis method. For the CB1 receptor blocking experiment, 7 ICR mice were divided into blocking group ( n=4; rimonabant for blocking treatment) and control group 1 ( n=3; no rimonabant blocking treatment). The affinity and specificity of 18F-SQKJ-2 for CB1 receptors were analyzed based on the differences in 18F-SQKJ-2 uptake (percentage injected dose per gram of tissue, %ID/g) by various organs between two groups. The metabolic stability of 18F-SQKJ-2 in vitro was studied using animal tissue homogenates. Ten C57 mice were used to establish fear memory mouse models (fear group, n=6; control group 2, n=4), and the percentage of freezing time was compared between 2 groups. MicroPET scans were used to detect the intracranial distribution of 18F-SQKJ-2, and the relative uptake in each brain region compared to total brain uptake was calculated. Statistical analysis was conducted to compare the differences in CB1 receptor relative total brain uptake in fear-related brain regions between 2 groups. Independent-sample t test and Mann-Whitney U test were used to analyze the data. Results:18F-SQKJ-2 was successfully synthesized with a radiochemical purity ≥98.0% and a corrected radioactive yield of (12.3±6.0)%( n=4). In vitro metabolic stability experiments showed that 18F-SQKJ-2 was basically stable in the liver, blood, and brain within 60min. The CB1 receptor blocking experiment demonstrated that the uptake of 18F-SQKJ-2 in the brains of mice in blocking group was significantly lower than that in control group 1 ((0.95±0.28) vs (3.44±1.16) %ID/g; t=-3.57, P=0.023). The percentage of freezing time in fear group was significantly higher than that in control group 2 (43.28%(39.46%, 52.93%) vs 2.74%(1.52%, 4.85%); Z=-2.45, P=0.010). 18F-SQKJ-2 microPET imaging showed that the uptake of 18F-SQKJ-2 in the cerebral cortex of mice in fear group was significantly increased compared with that in control group 2 ((5.83±0.47)% vs (5.00±0.52)%; t=2.42, P=0.046). Conclusion:18F-SQKJ-2 is successfully prepared with acceptable radiochemical purity and metabolic stability, demonstrating potential for visualizing and quantifying fear memory.
2.Development and characterization of 18F-SQKJ-2: a novel PET tracer for the diagnosis of fear memory disorders
Wanli HE ; Chenxin MA ; Xinghai CAO ; Junwei CHEN ; Yan GU ; Shuxia CAO ; Zhiqiang WANG ; Dilong MAO ; Qinggang HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(11):672-677
Objective:To develop and validate a novel PET tracer, N-cyclohexyl-4-((2, 4-dichlorophenyl)(4-(fluoro- 18F)phenyl)methyl)piperazine-1-carboxamide ( 18F-SQKJ-2), targeting cannabinoid type 1 (CB1) receptors for diagnosing psychiatric disorders associated with fear memory. Methods:18F-SQKJ-2 was prepared using a nucleophilic substitution radiochemical synthesis method. For the CB1 receptor blocking experiment, 7 ICR mice were divided into blocking group ( n=4; rimonabant for blocking treatment) and control group 1 ( n=3; no rimonabant blocking treatment). The affinity and specificity of 18F-SQKJ-2 for CB1 receptors were analyzed based on the differences in 18F-SQKJ-2 uptake (percentage injected dose per gram of tissue, %ID/g) by various organs between two groups. The metabolic stability of 18F-SQKJ-2 in vitro was studied using animal tissue homogenates. Ten C57 mice were used to establish fear memory mouse models (fear group, n=6; control group 2, n=4), and the percentage of freezing time was compared between 2 groups. MicroPET scans were used to detect the intracranial distribution of 18F-SQKJ-2, and the relative uptake in each brain region compared to total brain uptake was calculated. Statistical analysis was conducted to compare the differences in CB1 receptor relative total brain uptake in fear-related brain regions between 2 groups. Independent-sample t test and Mann-Whitney U test were used to analyze the data. Results:18F-SQKJ-2 was successfully synthesized with a radiochemical purity ≥98.0% and a corrected radioactive yield of (12.3±6.0)%( n=4). In vitro metabolic stability experiments showed that 18F-SQKJ-2 was basically stable in the liver, blood, and brain within 60min. The CB1 receptor blocking experiment demonstrated that the uptake of 18F-SQKJ-2 in the brains of mice in blocking group was significantly lower than that in control group 1 ((0.95±0.28) vs (3.44±1.16) %ID/g; t=-3.57, P=0.023). The percentage of freezing time in fear group was significantly higher than that in control group 2 (43.28%(39.46%, 52.93%) vs 2.74%(1.52%, 4.85%); Z=-2.45, P=0.010). 18F-SQKJ-2 microPET imaging showed that the uptake of 18F-SQKJ-2 in the cerebral cortex of mice in fear group was significantly increased compared with that in control group 2 ((5.83±0.47)% vs (5.00±0.52)%; t=2.42, P=0.046). Conclusion:18F-SQKJ-2 is successfully prepared with acceptable radiochemical purity and metabolic stability, demonstrating potential for visualizing and quantifying fear memory.
3.Clinical study of percutaneous vertebroplasty combined with 125I seeds implantation in the treatment of patients with thoracic metastatic tumor complicated with posterior vertebral defect
Tiying WANG ; Zuozhang YANG ; Jiahui CHEN ; Yan LIU ; Santosh KAMAR ; Qiuyun CHEN ; Tao YUAN ; Xinghai YANG ; Jing ZHANG ; Cao WANG ; Parsad Surendra YADAV ; Shrijan SHRESTHA ; Yihao YANG ; Dongqi LI
Chinese Journal of Oncology 2020;42(12):1056-1062
Objective:To analyze the safety and efficacy of percutaneous vertebroplasty combined with interstitial implantation 125I of seeds (PVPI) in the treatment of thoracic vertebroplasty with posterior vertebra defect. Methods:A retrospective analysis of the clinical data of 64 patients with thoracic spine metastases admitted to Yunnan Cancer Hospital from November 2017 to May 2019 was conducted, including 32 patients with posterior vertebra defect (experimental group) and 32 cases without (control group). Forty-two vertebral bodies of 32 patients in the experimental group were treated with improved PVPI surgery, which performed with the secondary sealing method and inclined puncture needle injection bone cement rotary filling technology, to reduce leakage. The 54 vertebral bodies of 32 patients in control group underwent PVPI. The two groups of patients were followed up on the second day, one month, three months and six months after the operation, and the short-term efficacy, long-term efficacy and safety indicators of the two groups were compared.Results:All 64 patients successfully completed the surgical treatment. The visual analogue scores and Karnofsky scores of the experimental group and the control group were improved to varying degrees on the second day, 1 month, 3 months and 6 months after the operation. There was no statistically significant difference between the two groups ( P>0.05). The amount of bone cement in the experimental group and control group was (2.36±0.20) ml and (2.39±0.17) ml, and the difference was not statistically significant ( P=0.482). The amount of 125I seed implantation was (30.63±0.91) and (32.56±0.68), respectively, the difference was not statistically significant ( P=0.925). The partial response rates of the study group and the control group were 81.3% and 87.5%, the stable disease rates were 12.5% and 9.4%, the differences were not statistically significant ( P>0.05). The median overall survival (mOS) of the study group was 13 months, and the median progression-free survival (mPFS) was 8 months. The mOS of the control group was 14 months, and the mPFS was 8 months. The differences were not statistically significant ( P>0.05). In the experimental group, 6 (14.3%) vertebral bodies had cement leakage, of which 2 (4.8%) were cement leakage at posterior vertebra, 4 (9.5%) were paravertebral cement leakage. Seven (13.0%) paravertebral cement leakage occurred in the control group. There was no significant difference in bone cement leakage between the two groups ( P=0.097). Bone cement leakage in both groups did not cause serious complications such as spinal cord injury and paraplegia. Conclusion:The application of PVPI in the treatment of thoracic metastatic tumor patients with posterior vertebra defect can acquire better clinical efficacy and safety through conduction of the improved intraoperative technology and paying more attention to the control of bone cement distribution and other issues.
4.Clinical study of percutaneous vertebroplasty combined with 125I seeds implantation in the treatment of patients with thoracic metastatic tumor complicated with posterior vertebral defect
Tiying WANG ; Zuozhang YANG ; Jiahui CHEN ; Yan LIU ; Santosh KAMAR ; Qiuyun CHEN ; Tao YUAN ; Xinghai YANG ; Jing ZHANG ; Cao WANG ; Parsad Surendra YADAV ; Shrijan SHRESTHA ; Yihao YANG ; Dongqi LI
Chinese Journal of Oncology 2020;42(12):1056-1062
Objective:To analyze the safety and efficacy of percutaneous vertebroplasty combined with interstitial implantation 125I of seeds (PVPI) in the treatment of thoracic vertebroplasty with posterior vertebra defect. Methods:A retrospective analysis of the clinical data of 64 patients with thoracic spine metastases admitted to Yunnan Cancer Hospital from November 2017 to May 2019 was conducted, including 32 patients with posterior vertebra defect (experimental group) and 32 cases without (control group). Forty-two vertebral bodies of 32 patients in the experimental group were treated with improved PVPI surgery, which performed with the secondary sealing method and inclined puncture needle injection bone cement rotary filling technology, to reduce leakage. The 54 vertebral bodies of 32 patients in control group underwent PVPI. The two groups of patients were followed up on the second day, one month, three months and six months after the operation, and the short-term efficacy, long-term efficacy and safety indicators of the two groups were compared.Results:All 64 patients successfully completed the surgical treatment. The visual analogue scores and Karnofsky scores of the experimental group and the control group were improved to varying degrees on the second day, 1 month, 3 months and 6 months after the operation. There was no statistically significant difference between the two groups ( P>0.05). The amount of bone cement in the experimental group and control group was (2.36±0.20) ml and (2.39±0.17) ml, and the difference was not statistically significant ( P=0.482). The amount of 125I seed implantation was (30.63±0.91) and (32.56±0.68), respectively, the difference was not statistically significant ( P=0.925). The partial response rates of the study group and the control group were 81.3% and 87.5%, the stable disease rates were 12.5% and 9.4%, the differences were not statistically significant ( P>0.05). The median overall survival (mOS) of the study group was 13 months, and the median progression-free survival (mPFS) was 8 months. The mOS of the control group was 14 months, and the mPFS was 8 months. The differences were not statistically significant ( P>0.05). In the experimental group, 6 (14.3%) vertebral bodies had cement leakage, of which 2 (4.8%) were cement leakage at posterior vertebra, 4 (9.5%) were paravertebral cement leakage. Seven (13.0%) paravertebral cement leakage occurred in the control group. There was no significant difference in bone cement leakage between the two groups ( P=0.097). Bone cement leakage in both groups did not cause serious complications such as spinal cord injury and paraplegia. Conclusion:The application of PVPI in the treatment of thoracic metastatic tumor patients with posterior vertebra defect can acquire better clinical efficacy and safety through conduction of the improved intraoperative technology and paying more attention to the control of bone cement distribution and other issues.
5.Effect observation of autogenous bone,allograft bone and BMP synthetic bone in treatment of lumbar spondylo-listhesis
Zhiyong LIN ; Renqian WEI ; Xinghai CAO ; Jiping ZHANG ; Tao GUO
Journal of Regional Anatomy and Operative Surgery 2016;25(6):420-423,424
Objective To explore the clinical effect of autogenous bone,allograft bone and BMP synthetic bone in the treatment of lum-bar spondylolisthesis,and provide more basis to choose transplant material.Methods A total of 96 patients with lumbar spondylolisthesis were chosen as research subjects,who were cured in our hospital from January 2014 to January 2015.They were divided into group A(who were treated with autogenous bone),group B(who were treated with allograft bone)and group C(who were treated with BMP synthetic bone), according to prospective study method.The indicators of the operation,postoperative adverse reactions,change of intervertebral disc height and bone graft fusion rate of three groups were compared.Results Difference of the operation indexes of three groups had no statistical sig-nificance(P >0.05).The incidences of adverse reactions in group A and group C had no statistically significant difference(P >0.05),but both less than that in group B,with statistically significant difference(P <0.05).The intervertebral disc height after 6,9,12 and 18 months in group A and group C had no statistically significant difference(P >0.05),but both more than that in group B,with statistically significant difference(P <0.05).Bone graft fusion rate of group C was faster than that of group A and goup B,and the graft fusion rate in 18 month in group A and C had no statistically significant difference(P >0.05).And the fusion rates of group A and C in each period were significantly higher than that of group B,with statistically significant difference(P <0.05).Total effective rate of neurologic improvement in group A and group C had no statistically significant difference(P >0.05),but both better than that of group B,with statistically significant difference (P <0.05).Conclusion BMP synthetic bone used in lumbar spondylolisthesis has the same clinical effect as autologous bone.But BMP synthetic bone has faster bone graft fusion rate than autologous bone.And it is beneficial to patients’recovery.

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