1.Research of Al 18F-labeled novel cyclic peptide probe Al 18F-FAP-NOX in tumor-targeted molecular imaging
Ziqi ZHANG ; Shaoyu LIU ; Jiawei ZHONG ; Ruiyue ZHAO ; Shuang XIONG ; Meijuan ZHOU ; Yimin FU ; Huizhen ZHONG ; Xinlu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):82-87
Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.
2.Preliminary clinical study of a novel FAP-targeted PET tracer 64Cu-FAPI-XT117 in malignant solid tumors: a comparative study with 18F-FDG
Xi HE ; Meijuan ZHOU ; Peng HOU ; Kaixiang ZHONG ; Youcai LI ; Jie LYU ; Miao KE ; Ruiyue ZHAO ; Shaoyu LIU ; Yimin FU ; Huizhen ZHONG ; Xinlu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(12):708-713
Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.
3.Research of Al 18F-labeled novel cyclic peptide probe Al 18F-FAP-NOX in tumor-targeted molecular imaging
Ziqi ZHANG ; Shaoyu LIU ; Jiawei ZHONG ; Ruiyue ZHAO ; Shuang XIONG ; Meijuan ZHOU ; Yimin FU ; Huizhen ZHONG ; Xinlu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):82-87
Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.
4.Preliminary clinical study of a novel FAP-targeted PET tracer 64Cu-FAPI-XT117 in malignant solid tumors: a comparative study with 18F-FDG
Xi HE ; Meijuan ZHOU ; Peng HOU ; Kaixiang ZHONG ; Youcai LI ; Jie LYU ; Miao KE ; Ruiyue ZHAO ; Shaoyu LIU ; Yimin FU ; Huizhen ZHONG ; Xinlu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(12):708-713
Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.
5.Effect of resveratrol combined with radiotherapy on cervical cancer Hela cell growth and migration by regulating PI3K/Akt/mTOR signaling pathway
Jianfu ZHANG ; Yunjun ZHANG ; Bengui JIANG ; Haibing MEI ; Huizhen ZHONG
Chinese Journal of Radiation Oncology 2021;30(9):956-960
Objective:To evaluate the effect of resveratrol combined with γ-ray irradiation on the biological behavior of cervical cancer cells, and to explore its possible mechanism.Methods:The proliferation of cell populations after different concentrations of resveratrol solution±γ-ray irradiation was detected by CCK-8 assay. Scratch test and Transwell chamber test were used to detect cell migration and invasion. Flow cytometry and Annexin V-FITC/PI double staining were employed to assess cell apoptosis. Western blot was performed to measure the expression levels of PI3K, Akt, p-Akt, mTOR and p-mTOR proteins.Results:Compared with the normal control (NC) group, the resveratrol group±γ-ray irradiation could inhibit the proliferation, migration, and invasion and promote cell apoptosis of human cervical cancer Hela cells, and the combined effect was more obvious. Compared with the NC group, resveratrol and γ-ray irradiation could significantly down-regulate the expression levels of Bcl-2, PI3K, p-Akt and p-mTOR proteins, up-regulate the expression level of Bax protein, but did not significantly alter the expression levels of Akt and mTOR proteins in human cervic1 255al cancer Hela cells.Conclusions:Resveratrol combined with γ-ray irradiation can dramatically inhibit the proliferation, migration, invasion, and promote the apoptosis of cervical cancer Hela cells. The mechanism may be related to the inhibition of the PI3K/Akt/mTOR signaling pathway and down-regulating the expression levels of downstream related proteins.
6.Effect of complete decongestive therapy in severe grade Ⅲ lower limb lymphedemabv
Lijuan ZHANG ; Qiaoling ZHONG ; Huizhen ZHANG ; Qinghua LUO ; Feng LIU ; Hailin TANG ; Huiying QIN
Chinese Journal of Practical Nursing 2020;36(27):2148-2155
Objective:To investigate the effect of complete decongestive therapy in the treatment of severe grade Ⅲ lower limb lymphedema.Methods:From January 2018 to December 2018, The patients were admitted to the lymphedema clinic of the cancer prevention and treatment center of Sun Yat-sen University, seven patients with severe gradeⅢ lower limb lymphedema were intervened with complete decongestive therapy, including problem skin care, special techniques of unarmed lymphatic drainage, foam block bandage combined with air wave pressure therapy, filled elastic bandage pressure bandage, functional exercise combined with home bare-handed lymphatic drainage and weight loss management. The intervention had two courses, and 20 times was a course of treatment. Perimeter measurement and weight measurement were used to evaluate the therapeutic effect at the 0, 5, 10, 15, 20, 30, 40 times of treatment.Results:After two courses of treatment, the circumference value of each measurement point on the affected side was lower than that before treatment, and the difference was statistically significant ( F values were 7.449-23.073, P < 0.05). The circumference value of the affected side decreased by 7.10 - 24.53 cm, and the weight after treatment was 9.0 - 20.5 kg less than that before treatment. During the follow-up period, it was found that the lower extremity diameter value at 3 months of follow-up at 5 sites increased and tended to be stable compared with that at 1 year of follow-up. Conclusion:Step 6 comprehensive swelling treatment can obviously improve the symptoms of patients with lower limb lymphedema of this research, and in the subsequent follow-up found that self-therapy at home, no recurrence or aggravate the limb swelling degree, and can reduce or stability treatment effect, enhance confidence in the treatment of patients, so as to improve the quality of life of patients and treatment compliance.
7.Application of dynamic multi-dimensional management model based on informatization on improving home self-care of patients with lymphedema
Qiaoling ZHONG ; Lijuan ZHANG ; Huizhen ZHANG ; Huiting ZHANG ; Qinghua LUO ; Jing CHEN ; Hailin TANG
Chinese Journal of Practical Nursing 2020;36(31):2405-2410
Objective:To explore the effect of dynamic multi-dimensional management model based on informatization on improving the home self-care of lymphedema patients.Methods:A total of 80 patients who received lymphedema combined detumescence treatment from January 2018 to June 2018 were selected as the control group.From July 2018 to December 2018, 80 patients were treated as the intervention group, and the whole process was managed on the basis of the control group using the dynamic multidimensional management mode based on informatization. Patients' compliance and quality of life were compared between the two groups.Results:The intervention group patients' compliance was better than control group, correctly measure the circumference of limbs, the law of life that occupy the home was good, correct manual lymph drainage direction, bandages, functional exercise, 18 standards compliance, respectively, 95.0%(76/80), 87.5%(70/80), 97.5%(78/80), 95.0%(76/80), 100.0%(80/80), 87.5%(70/80), better than that of control group were 77.5%(62/80), 75.0%(60/80), 80.0%(64/80), 70.0%(56/80), 75.0%(60/80), 50.0%(40/80), difference was statistically significant ( χ2 values were 4.103-26.182, P<0.05 or 0.01). After a course of treatment and 3 months of home-based self-care, the scores of role function, physical function, emotional function and social function of the quality of life in the intervention group were (75.44 ± 2.78), (80.11 ± 3.01), (78.25 ± 2.78), (79.93 ± 5.43), which were better than those of the control group (66.25 ± 2.58), (75.88 ± 3.57), (65.16 ± 2.47), (62.78 ± 4.01), with statistically significant differences ( t values were 8.09, 31.50, P<0.01). Conclusions:The dynamic multi-dimensional management model based on informationization and doctor-patient participation can improve the compliance and quality of life of patients participating in home-based self-care and better meet the needs of home-based nursing.
8. A study of the effect of case management on postoperative lymphedema in breast cancer patients
Huiting ZHANG ; Huizhen ZHANG ; Qiaoling ZHONG ; Huiying QIN ; Lijuan ZHANG
Chinese Journal of Practical Nursing 2019;35(33):2605-2611
Objective:
To explore the effect of case management on postoperative affected limb lymphedema in breast cancer patients.
Methods:
This study is a non-concurrent control trial. A total of 157 cases of breast cancer patients who met the inclusion/exclusion criteria were selected from the Sun yet-sen University Cancer Center from June 2016 to July 2017 and from June 2016 to July 2017 by the convenient sampling method. Among them, 80 patients from June to July 2016 were listed as the control group, and 77 patients from June to July 2017 were listed as the intervention group. The control group implemented the routine nursing mode of breast cancer. The intervention group implemented case management on the basis of routine nursing. Lymphedema of the affected limb were compared between the two groups before intervention, 3 months after surgery, 6 months after surgery and 1 year after surgery.
Results:
The incidence of postoperative lymphedema (
9.Outcome of re-pregnancy in women with uterine artery embolization for postpartum hemorrhage.
Xiaoxiao LIN ; Daifei SUN ; Jun FU ; Huizhen ZHONG
Journal of Zhejiang University. Medical sciences 2019;48(5):540-545
OBJECTIVE:
To evaluate the outcome of re-pregnancy in women with uterine artery embolization(UAE)for postpartum hemorrhage(PPH).
METHODS:
Clinical data of 117 pregnant women with previous PPH admitted in Ningbo Women and Children's Hospital from January 2010 to January 2016 were retrospectively analyzed. Among them 40 cases were treated with UAE (UAE group) and 77 cases were not treated with UAE (control group). The outcomes of re-pregnancy were followed up and compared between two groups.
RESULTS:
There were significant differences in the incidence of induced abortion in early pregnancy and cesarean scars pregnancy (CSP) between the two groups (<0.05 or <0.01). In the UAE group, the incidence of PPH, placental accretion and hysterectomy rate was significantly higher than that of control group (<0.05 or <0.01). Multivariate analysis showed that UAE was independent risk factor for CSP, placenta accretion, PPH and hystere-ctomy (<0.05 or <0.01).
CONCLUSIONS
The overall fertility and re-pregnant outcomes in women with previous UAE for PPH are favorable. However, the risk of CSP, placenta accretion and associated recurrence of PPH and hysterectomy is higher in women receiving UAE during subsequent pregnancy.
Abortion, Induced
;
Child
;
Female
;
Humans
;
Hysterectomy
;
Postpartum Hemorrhage
;
Pregnancy
;
Retrospective Studies
;
Treatment Outcome
;
Uterine Artery Embolization
10.Effect of hyperbaric oxygen therapy on postoperative cognitive dysfunction in elderly patients undergoing general anesthesia
Mingzhou LIU ; Meili WANG ; Lixin ZHANG ; Shuping CAO ; Huizhen MA ; Dunyi QI ; Wei REN ; Junli CAO ; Jianping ZHONG ; Xiangzhao XU ; Bin MA
Chinese Journal of Anesthesiology 2018;38(6):648-651
Objective To evaluate the effect of hyperbaric oxygen (HBO) therapy on postoperative cognitive dysfunction (POCD) in elderly patients undergoing general anesthesia.Methods A total of 112 patients,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective non-cardiac surgery with general anesthesia,were randomly divided into control group (C group,n =54) and HBO group (n =58).Patients were exposed to hyperbaric oxygen in a hyperbaric oxygen chamber once a day from day 3 to day 12 after surgery in both groups.Pressure was slowly increased to 2 atmosphere absolute within 20 min,pure oxygen was inhaled for 35 min by mask,5 min later pure oxygen was inhaled for another 35 min,oxygen inhalation was then stopped and pressure was slowly increased to 1 atmosphere absolute in HBO group.Patients inhaled air at 1 atmosphere absolute for 70 min in C group.Cognitive function score was assessed using Mini-Mental State Examination,language ability test,visual identification function test,digit span backwards task and Hasegawa's Dementia Scale (HDS) at 2 days before surgery and 7 and 13 days after surgery.The development of POCD was recorded.Results Compared with the baseline at 2 days before surgery,language ability test,digit span backwards task and HDS scores were significantly decreased at 7 and 13 days after surgery in C group,and digit span backwards task scores were significantly decreased at 7 days after surgery in HBO group (P<0.05 or 0.01).The language ability test and HDS scores were significantly higher,and the incidence of POCD was lower at 7 and 13 days after surgery in HBO group than in C group (P<0.05).Conclusion HBO therapy can reduce POCD in elderly patients undergoing general anesthesia.

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