Objective:To synthesize 177Lu-prostate-specific membrane antigen (PSMA)-617 with domestic 177Lu (made in China), and explore its optimal labeling condition, biodistribution, stability, and safety. Methods:177Lu-PSMA-617 was prepared with domestic 177Lu by a manual method. The optimal labeling condition, radiochemical purity, stability ( in vivo and in vitro), lipid-water partition coefficient, and plasma protein binding rate were determined. The uptake rate of 177Lu-PSMA-617 was evaluated by using 22RV1 cells. Biodistribution and SPECT/CT imaging were performed on normal mice with imported 177Lu-PSMA-617 as control group. The blood routine test was performed to evaluate the safety. Results:The best labeling result of domestic 177Lu-PSMA-617 can be obtained under the following conditions: pH=4.5, 100 ℃ for 30 min. And the radiochemical purity was ≥99%. The product was stable in vivo and in vitro, with the radiochemical purity >95% in 72 h. The plasma protein binding rate was (35.3±5.3)%, the lipid-water partition coefficient was -2.27±0.06, and the specific uptake rate of domestic 177Lu-PSMA-617 by 22RV1 cells reached the highest in 1 h ((7.58±0.84)%), which was slightly lower than the imported 177Lu-PSMA-617 ((7.86±0.96)%), but there was no significant difference between them ( t=-0.439, P>0.05). The distribution and SPECT/CT imaging of normal mice showed that domestic and imported 177Lu-PSMA-617 in blood were cleared quite fast, and both of them were excreted mainly through the kidneys. No obvious adverse reactions were found in the toxicity test of domestic and imported 177Lu-PSMA-617. There was no obvious abnormality in blood routine and liver and kidney metabolism. Conclusion:The domestic 177Lu-PSMA-617 has many advantages, such as qualified quality control, good biological properties and safety, which support its potential application value in diagnosis of prostatic neoplasms.

Objective To assess the reinforcing effect and operability of DNV-1929 in canine lungs so as to provide scientific basis for its clinical application by observing its characterisation during surgical resection.Methods Fifteen Beagles of 10-to 15-month-old,randomly assigned to three experimental groups,were used in this study for implantation experiments with DNV-1929 and negative control material.The experimental animals were housed in a defined environment and detailed clinical observations were made before and after the experiments.By using specific surgical techniques,the materials were implanted into different parts of the left lung of the dogs and their pressure resistance was assessed by airway pressure tests.The handling properties of the implanted materials were also evaluated.At weeks 2 and 4 after implantation,macroscopic visual observations and pathological examinations were performed on three sites of the canine left lung,the posterior anterior anterior lobe,the anterior posterior lobe,and and the posterior posterior lobe,in order to compare the tissue response of DNV-1929 with that of the negative control material.In addition,all experimental animals were evaluated for safety,including monitoring of clinical signs,food intake,and body weight.Results At airway pressure levels up to 35 hPa,both DNV-1929 and the negative control material showed similar pressure resistance with no gas leakage at the implantation site.During the procedure,DNV-1929 showed similar manoeuvrability to the negative control material,with no significant abnormalities observed.As seen by visual pathological observation after 2 and 4 weeks of implantation,both materials formed an encapsulation around the implantation site and underwent different degrees of adhesion with the thoracic organs,but the difference was not statistically significant(P＞0.05).There were more residual implants in the DNV-1929 group at 2 weeks and almost disappeared at 4 weeks of implantation,whereas a small amount of implanted material was still present in the negative control group,but residual material did not differ significantly between the two groups(P＞0.05).Histological evaluation showed that the subtotal score of inflammatory condition of DNV-1929 in the 2-week implantation group was slightly higher than that of the negative control substance(P=0.016),while the subtotal score of inflammatory condition in the 4-week implantation group was not statistically different compared with that of the negative control substance(P＞0.05).In terms of safety evaluation,the experimental dogs did not show any clinical abnormality or reduction in food intake during the study period,and there was no death on the day of implantation of DNV-1929 and the negative control substance.There was no significant change in body weight of the experimental dogs during the study cycle(P＞0.05).Conclusion DNV-1929 demonstrated a strengthening effect and good manoeuvrability in canine lungs with no toxic effects on surrounding tissues.This provides preliminary evidence for the use of DNV-1929 in surgical treatment of the lung,establishes scientific basis for its use in clinical practice,and demonstrates its potential value.

Objective:To explore the optimal labeling conditions of 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)- D-Phe1-Tyr3-Thr8-octreotide (TATE), and evaluate its biodistribution and imaging characteristics in mice. Methods:The reaction temperature, pH, reaction time and other labeling conditions were changed to realize the rapid labeling of NOTATATE by 177Lu. The optimal labeling conditions, radiochemical purity, in vitro stability, plasma protein binding rate, and lipid-water partition coefficient were determined. Twenty-four normal KM mice were divided into 6 groups by random number table method. After injected with 3.7 MBq 177Lu-NOTATATE through tail vein, they were sacrificed at 0.5, 1, 4, 24 h and 4, 6 d respectively to research the biological distribution (injection dose rate per gram of tissue percentage, %ID/g). Six normal mice were randomly divided into 2 groups and injected with 11.1 MBq 177Lu-NOTATATE and 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)TATE, respectively. SPECT planar imaging was performed at 1, 2, 3 h after injection. Another 8 mice were divided into 4 groups, injected with 3.7, 7.4, 18.5 MBq 177Lu-NOTATATE and saline respectively for an acute toxicity test. Results:At pH 5 and reaction temperature between 95 ℃ and 100 ℃ for 15 min, the labeling rate could reach more than 98%. After being placed in human serum for 24 h, the radiochemical purity was still higher than 95%. The plasma protein binding rate of 177Lu-NOTATATE was (58.6±1.9)% and the lipid-water partition coefficient was 0.048±0.014. In normal mice, the concentration of radioactivity is mainly in the liver, kidney and spleen, especially in the kidney (up to (29.120±1.204) %ID/g after 0.5 h of injection), which is less distributed in the blood and excreted rapidly. Compared with 177Lu-DOTATATE, 177Lu-NOTATATE was excreted faster by the kidney. The toxicity study results revealed that no damage was observed in mice of each group, and no obvious damage or inflammatory changes were observed in organ tissue sections. Conclusions:The optimal labeling condition of 177Lu-NOTATATE were determined in this study. The physical, chemical, and biological properties of 177Lu-NOTATATE were proved to be good and safe, and it was excreted faster by the kidney than 177Lu-DOTATATE. The results of this study lay a foundation for further clinical transformation research.

Objective To investigate the causal relationship between walking pace(WP)with interver-tebral disc degeneration(IVDD)and low back pain(LBP)by using two-sample Mendelian randomisation(MR)analysis method.Methods A genome-wide association study database of WP,IVDD and LBP was ob-tained,and single nucleotide polymorphisms(SNP)strongly associated with exposure were obtained as the in-strumental variables.The two confounders of smoking and sedentary were conservatively removed,and the MR analyses were performed by inverse variance weighting(IVW),weighted median,and MR-Egger methods to assess the causal relationship between WP with IVDD and LBP.The consistency and accuracy of results were ensured by heterogeneity,diversity tests,MR-PRESSO and negative control.Results The I VW results showed a significant negative correlation between WP and IVDD(OR=0.348,95％CI:0.183-0.661,P=0.001)and vice versa(OR=0.972,95％CI:0.953-0.992,P=0.007).Meanwhile there was also a significant negative correlation between WP and LBP(OR=0.214,95％CI:0.119-0.385,P＜0.001),but no causal re-lationship was found between LBP and WP.Conclusion Faster WP could effectively prevent the occurrence of IVDD and LBP,and IVDD may contribute to the occurrence of slow walking.

[Objective] To analyze the prevalence of human T-lymphocyte leukemia virus (HTLV) among blood donors in Guangzhou from 2016 to 2021, and provide a basis for blood collection and supply management in this region. [Methods] A total of 2 116 951 voluntary blood donors were screened for anti-HTLV by enzyme-linked immunosorbent assay (ELISA) from March 2016 to December 2021 in Guangzhou, and the reactive cases were further confirmed by Western blotting (WB). Qualitative data were analyzed by χ2 with spss19 software. The trend of the total positive rate of HTLV confirmation test by WB from 2016 to 2021 was analyzed with the Joinpoint software, and the annual percent change (APC) was used to determine whether the trend changes were statistically significant. [Results] From March 2016 to December 2021, the total positive rate for anti-HTLV by ELISA among voluntary blood donors in Guangzhou was 0.019 7% (416/ 2116 951), and the WB confirmed positive rate was 0.001 1% (23/2 116 951). The total positive rate of HTLV among individual voluntary blood donors in the six main districts (0.002 12%, 19/895 301) was higher than that among group voluntary blood donors (0.000 32%, 3/951 947) (P<0.05). There was no significant difference in the total positive rate of HTLV confirmation between the six main districts (0.001 19%) and the three non-main districts (0.000 37%) (P>0.05). The trend of the total positive rate of HTLV infection in the six main districts and the Guangzhou area(including the six main districts and three non-main districts) showed no significant increase or decrease. [Conclusion] The prevalence of HTLV among blood donors in Guangzhou remains at a low level.