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Objective:To assess the performance of Al 18F-prostate specific membrane antigen (PSMA)-BCH PET/CT in the detection and localization of early recurrent prostate cancer after radical prostatectomy. Methods:From July 2021 to July 2022, a cohort of 51 patients (age: 49-80(64.8±6.9) years) who underwent Al 18F-PSMA-BCH for biochemical recurrence with the prostate specific antigen (PSA) level less than 2 μg/L in Peking University Cancer Hospital & Institute were retrospectively analyzed. The patients were stratified into 4 groups (PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L, 1 μg/L≤PSA<2 μg/L groups) according to different PSA levels. Lesions detected by Al 18F-PSMA-BCH PET/CT were recorded as prostate bed (including bed of seminal vesicles); pelvic, paraaortic, mediastinal/supraclavicular and axillary lymph nodes; bone lesions and visceral lesions. The detection rates among different groups were compared by Fisher exact test. Results:Of 51 patients, 30(58.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer, with 60.0%(18/30) had disease confined to the pelvis, including 26.7%(8/30) had prostate bed recurrence, 26.7%(8/30) had pelvic lymph nodes, 6.6%(2/30) had prostate bed recurrence with pelvic lymph nodes, while 40.0%(12/30) had extra pelvic disease. The detection rates of Al 18F-PSMA-BCH PET/CT in PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L and 1 μg/L≤PSA<2 μg/L groups were 39.1%(9/23), 6/11, 8/9 and 7/8, respectively. There were no significant differences of detection rates between PSA<0.2 μg/L group and 0.2 μg/L≤PSA<0.5 μg/L group ( P=0.397) and also between 0.5 μg/L≤PSA<1 μg/L group and 1 μg/L≤PSA<2 μg/L group ( P=0.929). Conclusion:Al 18F-PSMA-BCH has a high detection rate for early recurrent prostate cancer, even at low PSA levels less than 0.2 μg/L.
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Objective:To prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al 18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability. Methods:Al 18F-PSMA-136 was prepared by replacing the phenyl of Al 18F-PSMA-137 with cyclohexyl in 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA). The inhibition abilities of PSMA of NOTA-PSMA-136 and NOTA-PSMA-137 were determined by N-acetylated-α-linked acidic dipeptidase (NAALADase) method. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio-high-performance liquid chromatography. The PSMA specificity and tumor targeting capability of the probes were investigated in 22Rv1 (PSMA positive-expressing) cells and mouse models. Independent-sample t test was used to analyze the data. Results:The Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al 18F-PSMA-136 was (30.1±8.4)% and the specific activity was (18.7±5.3) GBq/μmol. The radiochemical purities of the two probes were both greater than 95% and the stabilities in vitro were both good. Both probes showed PSMA-specific in 22Rv1 cells, but the uptake of Al 18F-PSMA-137 was significantly higher than that of Al 18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×10 5 cells (%IA/1×10 5 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×10 5 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al 18F-PSMA-136 and Al 18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al 18F-PSMA-137 in tumor was significantly higher than that of Al 18F-PSMA-136 (1 h: 1.78±0.10 vs 0.54±0.08; t=13.29, P<0.001; 2 h: 1.95±0.01 vs 0.52±0.11; t=18.53, P<0.001). Conclusion:Changes in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al 18F-PSMA-137 with strong lipophilicity is superior.
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Objective:To prepare a novel molecular imaging probe targeting angiotensin converting enzyme (ACE) 2 by using 68Ga labeled with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-DX600, then the probe was evaluated in cervical cancer model by microPET/CT imaging. Methods:68Ga labeled DOTA-DX600 at 95 ℃, and the quality control, stability in vitro and lipid-water partition coefficient (log P) were tested. Tumor-bearing mouse models were constructed using stably transfected ACE2 highly expressed cervical cancer cells (Hela). The distribution and uptake of 68Ga-DOTA-DX600 in normal KM mice and tumor-bearing mice were determined by microPET/CT imaging, and the maximum standardized uptake value (SUV max) of the main organs and tumors were obtained by semi-quantitative analysis of the region of interest (ROI). Results:The preparation time of 68Ga-DOTA-DX600 was about 20 min, the specific activity of the probe was (18.74±3.72)×10 6 GBq/mol, the labeling rate was 82.3%, and the radiochemical purity was about 99% after purification. After placement in saline or 5% human serum albumin (HSA) solution at room temperature for 2 h, the radiochemical purity of the probe was more than 96%. The lipid-water partition coefficient (log P) was -2.44 ±0.04 ( n=3), which indicated as a good hydrophilicity. In normal KM mice, 68Ga-DOTA-DX600 metabolized faster in the blood and mainly distributed in the kidneys. The probe showed good tumor targeting ability in the tumor-bearing mice and the SUV max of the tumor were 0.25±0.01 and 0.21±0.01 at 30 min and 60 min after injection, respectively, and the tumor uptake was inhibited by DX600. Conclusion:68Ga-DOTA-DX600 can be obtained conveniently and fast and shows a good targeting ability to tumors, which provide potential application value for researches on targeting ACE2.
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Laboratory test is the routine method of diagnosis, monitoring and blood screening of HIV infection, and main basis for early diagnosis of AIDS. HIV is divided into HIV-1 and HIV-2 subtypes, HIV-1 infection is the major cause of AIDS pandemic, while HIV-2 infection occurs in limited areas in the world, mainly in West Africa. HIV-2 infection has been reported in China since 1998. They are sporadic cases, and mainly HIV-1/HIV-2 mixed infections. There are less concerns about HIV-2 detection in China at present, and domestic HIV-2 detection reagents have not come into the market. At present, the detection method of HIV-2 is mainly antibody test and nucleic acid test. The initial screening is through rapid test and other methods and the confirmation is depended on Western Blot and Line Immune Assay. According to the HIV antibody test results, HIV-2 infection is confirmed. With the rapid development of molecular biology, the diagnostic method of nucleic acid detection laboratory has made great progress.
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Objective To observe the effect of DA-JC1 on the circadian rhythm disorder in C57BL/6 mice and the abnormal expression of period1 in HT22 cells induced by amyloid β-protein 31-35 (Aβ31-35).Methods (1) The six-eight weeks old C57BL/6 male mice were selected for wheelrunning behavior experiment.Then we analyzed the effect of DA-JC1 on the circadian rhythm disorder induced by Aβ31-35.(2) HT22 mouse hippocampal cells were adopted as the research objects.Cells were divided into vehicle group,Aβ31-35 group,pre-DA-JC1 group and DA-JC1 group (n =4 respectively) by random number table method.Cell viability was assessed by methylthiazolyldiphenyl-tetrazolium bromide cytotoxicity assay.Real-time quantitative PCR was used to detect the expression of clock gene period1,and Western blotting was applied to examine the expression of period1 protein at circadian time (CT) 12.Results (1) Compared with the vehicle group ((23.54 ± 0.07) h),the circadian rhythm of mice in the Aβ31-35 group was disturbed which exhibited significantly longer free running period ((23.80 ± 0.06) h,t=0.265,P=0.010),whereas the disruption was significantly relieved with pre-treatment of DA-JC1 ((23.61 ± 0.06) h,t =0.193,P =0.047).(2) Compared with the vehicle group (100.0％ ± 3.6％),5 μmol/L Aβ31-35 decreased the cell viability significantly (78.7％ ± 3.4％,t =12.393,P =0.005),and DA-JC1 can reduce the toxicity of Aβ31-35 in HT22 cells (89.2％ ± 2.3％,t =9.748,P =0.048).(3) Compared with the vehicle group (period1 gene:1.00 ± 0.09;period1 protein:1.01 ± 0.07),abnormal rhythmic expression of period1 was induced by Aβ31-35 in HT22 cells which significantly decreased at CT12 (period1 gene:0.58 ± 0.04,t =0.419,P =0.001;period1 protein:0.74 ± 0.07,t =0.221,P =0.007) while DA-JC1 pre-treatment can reverse the abnormal expression (period1 gene:0.79 ±0.11,t =0.279,P=0.024;period1 protein:0.99 ±0.05,t=0.226,P=0.009).Conclusion DA-JC1 improves the circadian rhythm disorder induced by Aβ31-35 in C57BL/6 mice and improves the abnormal expression of period1 induced by Aβ31-35 in HT22 cells.
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<p><b>OBJECTIVE</b>To analyze the reason of biochemical suboptimal response in CHB patients with complete virological response after more than 2 years standard treatment with Nucleos(t)-ide analogs (NUCs).To evaluate the efficacy and safety profiles of bicyclol tablets plus on the basis of the original treatment and lifestyle intervention. in CHB patients complicated with fatty liver.</p><p><b>METHODS</b>In 40 patients with chronic hepatitis B meeting the inclusion criteria,the liver biopsy was conducted.And patients complicated with fatty liver were treated with bicyclol tablets (25 mg, t.i.d) additional consecutive 48 weeks. The changes of serum biochemistry indexes and liver fibrosis index were observed before and after treatment.</p><p><b>RESULTS</b>Among 40 patients, 27 were complicated with fatty liver(69.23%), fatty degree in liver cell and liver inflammatory were closely related to the advanced fibrosis (x² =4.746, P=0.029; x² =5.072, P=0.024). The expression of HBsAg in serum and liver tissue showed no correlation with the advanced fibrosis (x² = 0.273, P=0.601; x² = 0.020, P =0.887) After bicyclol tablets treatment, serum biochemistry of patients complicated with fatty liver significantly decreased (F=58.045, P =0.000), plasma GST-PX significantly increased (t=15.109, P =0.000), plasma MDA significantly decreased (t=-10.786, P=0.000); LSM significantly decreased (t=2.255, P=0.036; t =5.376, P =0.002).</p><p><b>CONCLUSION</b>For the antiviral purpose of guide treatment, CHB patients treated with Nucleos(t)-ide analogs (NUCs) with biochemical suboptimal response, other risk factors should be considered as early as possible. Bicyclol plus lifestyle intervention was effective for chronic hepatitis B combined fatty liver patients with poor biochemical responses.</p>