Objective:To investigate the additional value of 99Tc m-hydrazinonicotinamide (HYNIC)-Tyr3-octreotide (TOC) SPECT/CT imaging in the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:A total of 54 patients (28 males and 26 females, age: (52.6±11.7) years) who underwent enhanced CT (MR) and 99Tc m-HYNIC-TOC SPECT/CT in People′s Hospital of Zhengzhou University between December 2017 and June 2023 were analyzed retrospectively. Surgical pathology or biopsy was the gold standard of patients′ diagnosis (primary tumors), and comprehensive evaluation based on pathology, imaging and follow-up results was used as the diagnostic criteria of lesions. McNemar χ2 test was used to compare the diagnostic efficacy of different imaging methods. Results:Pathological results showed that 43 of the 54 patients were with GEP-NETs and 11 were with non-neuroendocrine tumors (NETs). The sensitivities of enhanced CT and enhanced MR in the diagnosis of patients with GEP-NETs were 65.1%(28/43) and 60.0%(15/25) respectively, which increased to 93.0%(40/43) and 92.0%(23/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 8.64, 4.90, P values: 0.002, 0.021). There were 22 and 15 patients showing atypical enhancement on enhanced CT and enhanced MR respectively. The sensitivities of these two methods for GEP-NETs in patients with atypical enhancement were 54.5%(12/22) and 8/15 respectively, which increased to 95.5%(21/22) and 14/15 with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.82, 4.17, P values: 0.012, 0.031). Compared with enhanced CT, the detection rates of liver and bone metastatic lesions were improved significantly from 90.8%(158/174) and 55.2%(32/58) to 96.6%(168/174) and 87.9%(51/58) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.79, 9.82, P values: 0.013, 0.001). Compared with enhanced MR, the detection rate of bone metastases was improved significantly from 56.0%(14/25) to 88.0%(22/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2=4.08, P=0.039). After 99Tc m-HYNIC-TOC imaging, stages were changed in 7.0%(3/43) of patients and a greater number or extent of metastases were detected in 11.6%(5/43) of patients. 99Tc m-HYNIC-TOC imaging detected additional recurrent or metastatic lesions in 40.0%(8/20) of patients during follow-up compared to enhanced CT. Conclusion:99Tc m-HYNIC-TOC imaging can provide an added value for diagnosing GEP-NETs with atypically enhanced CT(MR), and in the detection of liver metastasis and early bone metastasis, thus helping the optimization of clinical treatment strategies.

Objective:To investigate the additional value of 99Tc m-hydrazinonicotinamide (HYNIC)-Tyr3-octreotide (TOC) SPECT/CT imaging in the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:A total of 54 patients (28 males and 26 females, age: (52.6±11.7) years) who underwent enhanced CT (MR) and 99Tc m-HYNIC-TOC SPECT/CT in People′s Hospital of Zhengzhou University between December 2017 and June 2023 were analyzed retrospectively. Surgical pathology or biopsy was the gold standard of patients′ diagnosis (primary tumors), and comprehensive evaluation based on pathology, imaging and follow-up results was used as the diagnostic criteria of lesions. McNemar χ2 test was used to compare the diagnostic efficacy of different imaging methods. Results:Pathological results showed that 43 of the 54 patients were with GEP-NETs and 11 were with non-neuroendocrine tumors (NETs). The sensitivities of enhanced CT and enhanced MR in the diagnosis of patients with GEP-NETs were 65.1%(28/43) and 60.0%(15/25) respectively, which increased to 93.0%(40/43) and 92.0%(23/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 8.64, 4.90, P values: 0.002, 0.021). There were 22 and 15 patients showing atypical enhancement on enhanced CT and enhanced MR respectively. The sensitivities of these two methods for GEP-NETs in patients with atypical enhancement were 54.5%(12/22) and 8/15 respectively, which increased to 95.5%(21/22) and 14/15 with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.82, 4.17, P values: 0.012, 0.031). Compared with enhanced CT, the detection rates of liver and bone metastatic lesions were improved significantly from 90.8%(158/174) and 55.2%(32/58) to 96.6%(168/174) and 87.9%(51/58) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.79, 9.82, P values: 0.013, 0.001). Compared with enhanced MR, the detection rate of bone metastases was improved significantly from 56.0%(14/25) to 88.0%(22/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2=4.08, P=0.039). After 99Tc m-HYNIC-TOC imaging, stages were changed in 7.0%(3/43) of patients and a greater number or extent of metastases were detected in 11.6%(5/43) of patients. 99Tc m-HYNIC-TOC imaging detected additional recurrent or metastatic lesions in 40.0%(8/20) of patients during follow-up compared to enhanced CT. Conclusion:99Tc m-HYNIC-TOC imaging can provide an added value for diagnosing GEP-NETs with atypically enhanced CT(MR), and in the detection of liver metastasis and early bone metastasis, thus helping the optimization of clinical treatment strategies.

Objective:To investigate the efficacy and influencing factors of initial 131I therapy in serum thyroglobulin (Tg) antibody (TgAb)-positive patients with papillary thyroid cancer (PTC). Methods:A retrospective analysis was performed on the clinical data of 1 624 patients with PTC who underwent 131I therapy in Henan Provincial People′s Hospital between January 2017 and January 2023. The patients were divided into TgAb-positive group (246 cases (36 males, 210 females), age: 43.5(31.0, 52.0) years) and TgAb-negative group (1 378 cases (439 males, 939 females), age: 44.0(34.0, 53.0) years). The efficacy was evaluated 6-12 months post 131I therapy based on serological tests (TgAb, Tg) and imaging results (ultrasonography, CT, 131I-whole body scan (WBS), SPECT/CT imaging), and the patients were divided into disease persistence/recurrence and non-persistence/recurrence groups. The χ2 test was used to analyze the difference in efficacy between the TgAb-positive group and the TgAb-negative group. Among TgAb-positive patients, the clinical characteristics of disease persistence/recurrence group were compared with those of non-persistence/recurrence ones by χ2 test or Mann-Whitney U test, and the independent risk factors affecting the efficacy of 131I therapy were analyzed by binary logistic regression. Results:The disease persistence/recurrence were found in 38 cases (15.4%, 38/246) of the TgAb-positive group and 143 cases (10.4%, 143/1 378) of the TgAb-negative group, with a statistically significant difference between the two groups ( χ2=5.42, P=0.020). Among the TgAb-positive patients, statistically significant differences were found in lymph node metastasis (35 vs 23 cases), the interval between surgery and 131I therapy (2.0(1.5, 3.0) vs 2.3(2.0, 3.0) months), stimulated Tg(sTg) level before the initial 131I therapy (0.18(0.04, 5.78) vs 0.04(0.04, 0.46) μg/L), and TgAb level before the initial 131I therapy (40.15(19.13, 156.15) vs 22.25(7.53, 76.20) kU/L) between disease persistence/recurrence group and non-persistence/recurrence group ( χ2=117.13, z values: -2.29, -2.41, -2.80, all P<0.05). Lymph node metastasis was an independent risk factor (odds ratio( OR)=89.326, 95% CI: 25.005-319.106, P<0.001) for the efficacy of 131I therapy in patients with TgAb-positive PTC. Conclusion:The overall efficacy of 131I therapy in patients with TgAb-positive PTC is relatively poor, and lymph node metastasis is an independent risk factor for the efficacy of 131I therapy, while the level of TgAb is not an independent risk factor for the efficacy of 131I therapy in these patients.

Ten-eleven translocation 1 (TET1) protein is an alpha-ketoglutaric acid (α-KG) and Fe²⁺-dependent dioxygenase. It plays a role in the active demethylation of DNA by hydroxylation of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC). Ten-eleven translocation 1 (TET1) protein is involved in maintaining genome methylation homeostasis and epigenetic regulation. Abnormally expressed TET1 and 5-mC oxidative derivatives have become potential markers in various biological and pathological processes and a research focus in the fields of embryonic development and malignant tumors. This paper introduces the structure and demethylation mechanism of TET1, reviews the research status of epigenetic regulation by TET1 in embryonic development, immune responses, stem cell regulation, cancer progression, and nervous system development, and briefs the upstream regulatory mechanism of TET1, hoping to provide new inspirations for further research in related fields.
Proto-Oncogene Proteins/genetics* ; Epigenesis, Genetic ; Humans ; DNA-Binding Proteins/metabolism* ; DNA Methylation ; Mixed Function Oxygenases/metabolism* ; 5-Methylcytosine/analogs & derivatives* ; Animals ; Embryonic Development/genetics* ; Neoplasms/genetics* ; Dioxygenases/metabolism*

Objective:To investigate the value of 99Tc m-hydrazinonicotinamide (HYNIC)-prostate specific membrane antigen(PSMA) SPECT/CT imaging in biochemical recurrence of prostate cancer (PCa). Methods:From January 2018 to March 2023, 112 patients with biochemical recurrence of PCa (age (72.6±6.1) years) who underwent 99Tc m-HYNIC-PSMA SPECT/CT imaging in Henan Provincial People′s Hospital were retrospectively analyzed. According to the level of prostate specific antigen (PSA), patients were divided into 0.2 μg/L2 μg/L group. According to the Gleason score, patients were divided into Gleason score≥8 group and Gleason score <8 group. The detection rate between groups was analyzed by χ2 test, and the difference of the PSA level between groups was compared by Mann-Whitney U test. Results:PSMA imaging was positive in 77 cases and negative in 35 cases, with the detection rate of 68.8%(77/112). The detection rates of local recurrence, lymph node metastasis, bone metastasis and lung metastasis were 8.9%(10/112), 43.8%(49/112), 28.6%(32/112) and 0.9%(1/112), respectively. The detection rates of 0.2 μg/L2 μg/L groups were 44.7%(21/47), 8/12 and 90.6%(48/53), respectively ( χ2=24.44, P<0.001). The detection rates of Gleason score ≥8 group and <8 group were 76.4%(55/72) and 55.0%(22/40) ( χ2=5.47, P=0.032); the PSA level between the two groups was statistically different (3.11(0.75, 5.91) and 0.84(0.44, 2.92) μg/L; z=-2.99, P=0.003). Of the patients with PSMA positive imaging, 84.4%(65/77) changed their treatment regimen and 15.6%(12/77) continued to observe or maintain the original treatment plan. Of the patients with PSMA negative imaging, 40.0%(14/35) changed the treatment plan, 51.4%(18/35) continued to observe or maintain the original treatment plan, and 8.6%(3/35) discontinued the original treatment because no tumor metastasis was found. Conclusion:99Tc m-HYNIC-PSMA SPECT/CT imaging can provide reference for the lesion detection, treatment decision-making and follow-up observation of biochemical recurrence of PCa.

Objective:To summarize the clinical feature of functional distant metastasis (DM) of differentiated thyroid cancer (DTC) and observe the efficacy of 131I treatment. Methods:Between August 2008 and January 2021, a total of 13 DTC patients (4 males, 9 females; age 26-75 years) with functional DM from Henan Provincial People′s Hospital were retrospectively analyzed. Clinical data of patients were collected, including pathological type, metastasis size, metastasis location, and thyroid stimulating hormone (TSH) before the first 131I treatment. Efficacy of 131I treatment in patients with functional DM-DTC was evaluated by response evaluation criteria in solid tumors (RECIST) 1.1 and thyroglobulin (Tg). Complete remission (CR) and partial remission (PR) were considered as effective. Wilcoxon signed rank test was used to analyze the maximum diameter change of metastatic lesions before and after 131I treatment. Results:Among 13 DM-DTC patients, 8 were follicular thyroid cancer (FTC), 5 were papillary thyroid cancer (PTC). Metastasis lesions were mainly located in lungs ( n=12) and bones ( n=6). There were 12 patients with maximum metastasis diameter ≥1 cm, and 3 patients with TSH≥30 mU/L before the first 131I treatment. Nine patients were assessed as PR by RECIST 1.1, 3 patients were assessed as CR by RECIST 1.1 and the value of Tg, and 1 patient was assessed as PR by the changing of Tg. The effective rate of 131I treatment for patients with functional DM-DTC was 13/13. The maximum metastasis diameter was significantly decreased after 131I treatment (2.6(1.6, 3.3) vs 1.2(0.1, 2.2) cm; z=-3.06, P=0.002). Conclusion:Patients with functional DM-DTC are characterized by high proportion of FTC and the maximum metastasis diameter ≥1 cm, low proportion of TSH ≥30 mU/L before the first 131I treatment, and high effective rate of 131I treatment.

Objective:To explore the diagnostic value of quantitative 99Tc m-hydrazinonicotinamide(HYNIC)-prostate specific membrane antigen (PSMA) SPECT/CT in patients with prostate cancer. Methods:From November 2018 to March 2021, the data of 56 patients ((69.8±8.0) years) with clinically suspected prostate cancer, who had elevated radioactive uptake in prostate on 99Tc m-HYNIC-PSMA SPECT/CT images in Henan Provincial People′s Hospital, were retrospectively analyzed. According to the pathological results, patients were divided into prostate cancer group ( n=45) and non-prostate cancer group ( n=11). The xSPECT-QUANT software was used to quantitatively analyze the high uptake area of the prostate, and SUV max was measured. The independent-sample t test, Mann-Whitney U test, ROC curve and Spearman correlation analysis were used for data analysis. Results:The prostate cancer group had higher SUV max than non-prostate cancer group (10.79±5.96 vs 3.60±1.27; t=7.43, P<0.001). When SUV max≥6.46, the AUC of prostate cancer was 0.887, with the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 73.3%(33/45), 11/11, 100%(33/33), 47.8%(11/23), 78.6%(44/56), respectively. The SUV max of prostate cancer group was positively correlated with Gleason score ( rs=0.632, P<0.001). The SUV max of 29 patients with Gleason score≥8 was higher than that of 16 patients with Gleason score≤7 ( z=-3.89, P<0.001). There was no statistical difference in PSA level between patients with Gleason score≤ 7 and patients with non-prostate cancer ( z=-1.63, P=0.110), but the SUV max was significantly different ( z=-2.22, P=0.026). The SUV max of 23 patients with metastases was higher than that of 22 patients without metastasis (12.99±5.85 vs 8.50±5.28; t=2.69, P=0.010). ROC analysis showed that the AUC was 0.709; with SUV max≥13.02 as the threshold, the sensitivity for diagnosing prostate cancer metastases was 56.5%(13/23), the specificity was 86.4%(19/22), and the accuracy was 71.1%(32/45). Conclusions:The 99Tc m-HYNIC-PSMA SPECT/CT quantitative analysis is feasible in patients with prostate cancer. SUV max of 99Tc m-HYNIC-PSMA can be used in the diagnosis of prostate cancer, assessment of the malignancy and prediction of metastasis.

Objective:To investigate the clinicopathological characteristics and 18F-fluorodeoxyglucose (FDG) PET/CT imaging features of bronchopulmonary neuroendocrine tumors(BP-NETs) with different pathological subtypes. Methods:From January 2013 to May 2018, 280 patients (196 males, 84 females, median age 58 years) with BP-NETs proved by pathology in Henan Provincial People′s Hospital were retrospectively analyzed. Age, gender, smoking history, the location and size of tumor, Ki-67 positive index, thyroid transcription factor-1 (TTF-1), synaptophysin (Syn), chromogranin-A (CgA), CD56, maximum standardized uptake value (SUV max), lymph node metastasis and distant metastasis were compared among 4 pathological subtypes of BP-NETs, including typical carcinoid (TC), atypical carcinoid (AC), small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). One-way analysis of variance, χ2 test, Fisher exact test and Kruskal-Wallis rank sum test were used for data analysis. Results:There were significant differences in age, smoking history, tumor size and location, Ki-67 positive index, CgA, CD56, TTF-1, SUV max and TNM stage among TC( n=59), AC( n=21), SCLC( n=184) and LCNEC ( n=16) groups ( F values: 2.067, 3.358, H values: 17.749-22.351, all P<0.05). SCLC had the largest tumor size (5.5(3.0, 6.8) cm) and the highest proportion of central type (85.3%, 157/184), and were more prone to lymph node metastasis. LCNEC had the oldest age ((66±16) years), the largest proportion of smoking history (14/16) and peripheral type (12/16). CD56 in SCLC (95.7%, 176/184) and LCNEC(15/16) mostly showed positive expression, while the positive expression rates of CgA and TTF-1 were higher in TC and AC (96.6%(57/59), 93.2%(55/59) and 95.2%(20/21), 90.5%(19/21), respectively). The Ki-67 positive index and SUV max of the four subtypes were significantly different, with the highest in SCLC group and the lowest in TC group. Conclusion:Different pathological subtypes of BP-NETs manifest different clinicopathological features and imaging presentation on 18F-FDG PET/CT, which are useful for understanding their characteristics.

Objective:To prepare 68Ga-2-(4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)pentanedioic acid (NODAGA)-YHWYGYTPQNVI (GE11) and evaluate its feasibility of PET imaging for pancreatic cancer. Methods:GE11 peptide was conjugated with NODAGA and then labeled with 68Ga. The labeling yield, radiochemical purity, hydrophilicity, stability and specificity in vitro were determined. Human pancreatic cancer BxPC3 nude mice models ( n=9) were established. MicroPET imaging was then obtained after 30 and 90 min, and mice were sacrificed at 90 min to acquire the radioactivity distribution of main organs and tumors. Pair t test was used to analyze the data. Results:The labeling yield was (73.5±5.4)% and radiochemical purity was more than 98%. After incubation 120 min in mouse serum at 37 ℃, radiochemical purity was more than 92%. The uptake was specific in BxPC3 cell lines. MicroPET images showed that 68Ga-NODAGA-GE11 could accumulate quickly in tumor. Value of tumor uptake was significantly higher than that of normal pancreas at 90 min ((1.38±0.25) vs (0.49±0.07) %ID/g; t=12.67, P<0.05), and the radio-uptake of blood, muscle and bone was lower than that of tumor. Conclusions:68Ga-NODAGA-GE11 is easy to be prepared with high radiochemical purity and good stability, and can specifically target BxPC3 xenograft tumor. However, due to the high uptake in the kidneys and liver, the value of 68Ga-NODAGA-GE11 in PET imaging for pancreatic tumor needs further study.

Objective:To study the correlation between changes of cerebral striatal dopamine D 2 receptors non-displaceable binding potential (BP ND), functional connectivity (FC) and clinical symptoms in patients with first-episode major depressive disorder (MDD), by 11C-Raclopride PET/CT and resting state fMRI (rs-fMRI). Methods:Thirty-eight first-episode depression patients (MDD group) and forty healthy volunteers (control group) matched with age, gender and years of education were selected. All subjects were scored with Hamilton depression scale (24 versions) before enrollment.All the subjects underwent cerebral 11C-Raclopride PET/CT and rs-fMRI in resting state. MIAKAT and DPARSF were used to analyze BP ND of cerebral striatal dopamine D 2 receptors and FC of striatum and the whole brain in subjects, respectively. Changes of striatal dopamine D 2 receptors BP ND and striatum and the whole brain FC of MDD were analyzed, and correlations among BP ND, FC and Hamilton depression rating scale were calculated by Rest 1.8 and SPSS 20.0. Results:Compared with the control group, BP ND of bilateral caudate nucleus and putamen dopamine D 2 receptors in the MDD group were decreased(left caudate nucleus: 1.16±0.37 vs 1.48±0.39, right caudate nucleus: 1.21±0.31 vs 1.62±0.48, left putamen: 1.73±0.47 vs 2.21±0.66, right putamen: 1.79±0.46 vs 2.17±0.65, t=3.66, -4.42, -3.68, -2.91, all P<0.001). Besides, FC of left caudate nucleus and left medial prefrontal lobes(4.38±1.31, 2.35±0.48), left caudate nucleus and left middle frontal gyrus(3.36±1.11, 1.64±0.56), left caudate nucleus and left superior frontal gyrus(3.14±0.78, 1.64±0.53), left putamen and left medial prefrontal lobes(4.10±1.42, 2.42±0.64, t=6.82, P<0.05), right caudate nucleus and right medial prefrontal lobes (4.32±1.30, 2.33±0.63, t=8.51, P<0.05), right putamen and right medial prefrontal lobes(3.77±1.25, 2.31±0.63, t=6.49, P<0.05)in the MDD group were increased.FC of left putamen and left anterior cingulate(1.60±0.55, 2.68±0.84, t=-6.76, P<0.05), right caudate nucleus and right amygdala (1.67±0.57, 3.46±0.64, t=-8.27, P<0.05) in the MDD group were decreased. Furthermore, there were significant negative correlations between D 2 receptors BP ND of bilateral striatum and FC of the same lateral striatum and medial prefrontal lobes ( r=-0.66, -0.50, -0.67, -0.47, all P<0.05). In MDD group, FC in left caudate nucleus and left medial prefrontal lobe were positively correlated with total score of Hamilton depression scale and anxiety somatization( r=0.55, 0.68, P<0.001). FC in left putamen and left medial prefrontal cortex were positively correlated with cognitive impairment and retardation ( r=0.37, 0.40, P=0.021, 0.001). FC of right caudate nucleus and right medial prefrontal lobe were positively correlated with Hamilton depression scale total score and anxiety somatization ( r=0.52, 0.67, all P<0.001). FC in right putamen and right medial prefrontal cortex was positively correlated with cognitive impairment ( r=0.50, P=0.002). Conclusion:The abnormal BP ND of cerebral striatal dopamine D 2 receptor of patients with first-episode depression is related to the abnormal activity of dopamine reward circuit related neurons in patients with MDD, which was related to clinical symptoms of depression. It may be involved in the pathogenesis of depression.