Objectives: This study was aimed to investigate the gender-related differences of regional cerebral glucose metabolism in healthy people along the age using 18F-FDG PET/CT.Methods: We recruited 344 healthy volunteers, including 217 males and 127 females (age range: 40–89 years old). All subjects underwent fluorine-18 fluorodeoxyglucose(18F-FDG) positron emission tomography (PET). All the data were divided into four groups for every 10 years old. Each participant was carefully screened from PET, MR, and other examinations in order to exclude the abnormalities, such as neurodegenerative or psychiatric disorders, alcohol/abuse, cerebral vascular disorders, metabolic diseases like diabetes mellitus and hyperthyroidism, and other systemic malignancies. The 40–50 years old group was set as the baseline group. Statistical parametric mapping (SPM) analysis was employed to illustrate the differences among groups.Results: Compared to the baseline group, whether in a cohort or different gender groups, the decrease of brain glucose metabolism was shown in the bilateral frontal lobe, anterior cingulate gyrus, and the bilateral temporal lobe. In males, the regions of decreased metabolism were bilateral frontal lobe, caudate nucleus, and cingulate gyrus, whereas that of females were left occipital lobe, cerebellum, and the thalamus. However, the overall decrease of brain metabolism in men and women began from the age of 60s, an aggravated decrease from 70s was only observed in males.Conclusion: (1) An obviously decreased brain metabolism was found from 60 years old, especially in the bilateral frontal lobe, bilateral temporal lobe, and inferior cingulate gyrus; (2) We found specific brain metabolic differences between genders, including the caudate nucleus region in males and the occipital lobe region in females; and (3) The aging trend is different between genders.

Background. Recent studies suggest a correlation between the reduced Sirt‐1 expression with Alzheimer’s diseases (AD) and depression, respectively, suggesting a possible pathogenic role of the altered Sirt‐1 expression in neuronal degenerative diseases, such as AD and depression. However, the molecular mechanisms underlying how Sirt‐1 reduction impairs neuronal functions remain unknown. Methods. We used the SK‐N‐SH neuroblastoma cells to study the role of Sirt‐1 expression on physiological roles in neuronal cells. Gain of Sirt‐1 was achieved by transiently transfecting Sirt‐1 expression plasmid. Sirt‐1‐specific shRNA was used to elucidate the role of Sirt‐1 loss of function. CCK‐8 (Cell Counting Kit‐8) assay and flow cytometry were used to evaluate cell proliferation. Semiquantitative western blotting was used to detect relative protein levels. A further luciferase reporter gene assay was employed to examine the effect of Sirt‐1 expression on the transcriptional activity of p53. RT‐qPCR was used to determine the mRNA levels of p21, Bax, and Bcl‐2, which were the downstream target genes of p53. Results. Sirt‐1 suppressed the p53 downstream gene p21 transcription, while shRNA‐mediated Sirt‐1 knockdown resulted in a significant increase in p21 expression, implying a possibility that Sirt‐1 promotes neuron proliferation through suppressing p53 transcriptional activity. The mRNA and protein levels of p53 were not affected by the altered Sirt‐1 expression, suggesting that Sirt‐1 regulates the transcriptional regulatory activity of p53 rather than p53 expression. Indeed, we further confirmed that Sirt‐1 appeared to inhibit p53 transcriptional activity by attenuating its acetylation and resulted in a decrease of p53’s binding to the p21 promoter. Overexpressed Sirt‐1 scavenged reactive oxygen species (ROS) production in SK‐N‐SH with H₂O₂. Knockdown of Sirt‐1 presented opposite effect; the addition of EX527 (Sirt‐1 inhibitor) increased ROS accumulation. Conclusions. Oxidative stress induces Sirt‐1 in neuron cells, and Sirt‐1 promotes proliferation in SK‐N‐SH cells, which protects them from oxidative stress‐induced cell death, potentially via suppressing the transcriptional activity of p53. These results provide a molecular explanation underlying how the reduced Sirt‐1 potentially causes the AD and depression‐related diseases, supporting the idea that Sirt‐1 can possibly be used as a diagnostic biomarker and/or therapeutic drug target for the AD and depression‐related diseases.

Background: Long non-coding RNA (LncRNA) HOTAIR was amplified and overexpressed in many human carcinomas, which could serve as a useful target for cancer early detection and treatment. The ^99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to evaluate whether liposome-coated antisense oligonucleotide probe ^99mTc-HYNIC-ASON targeting HOTAIR can be used in in vivo imaging of HOTAIR in malignant glioma xenografts. Methods: The ASON targeting LncRNA HOTAIR as well as mismatched ASON (ASONM) were designed and modified. The radiolabeling of ^99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC (Instant thin-layer chromatography) and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after liposome-coated ^99mTc-HYNIC-ASON/ASONM were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software. Results: The labeling efficiencies of ^99mTc-HYNIC-ASON and ^99mTc-HYNIC-ASONM measured by ITLC were (91 ± 1.5) % and (90 ± 0.6) %, respectively, and both radiochemical purities were more than 89%. Two probes showed good stability within 12 h. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Biodistribution study demonstrated that liposome-coated antisense probes were excreted mainly through the kidney and bladder and has higher uptake in the tumor. Meanwhile, the tumor was clearly shown after injection of liposome coated ^99mTc-HYNIC-ASON, and its T/M ratio was higher than that in the non-transfection group and mismatched group. No tumor was seen in mismatched and blocking group. Conclusion: The liposome encapsulated ^99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of LncRNA HOTAIR expression in malignant glioma.

Fibroblast activation protein (FAP) is higher expressed on cancer-associated fibroblasts (CAFs) in most malignant epithelial neoplasms, which is lower expressed in normal tissues. As a promising small molecular probe, FAP inhibitor (FAPI) shows the specific binding to FAP. This study aimed to explore a novel molecular probe [^99mTc]Tc-HYNIC-FAPI targeting CAFs. The in vitro characteristics of the probe were also evaluated. The FAPI targeting FAP was designed, synthesized and conjugated with the chelator 6-hydrazinylnicotinic acid (HYNIC) for radiolabeling with ^99mTc. The radiolabeling yield, radiochemical purity and stability were evaluated by Instant thin-layer chromatography (ITLC) and High performance liquid chromatography (HPLC). Lipophilicity was performed by the distribution coefficient test. The binding and migration ability of the probe was assessed using the FAP transfected tumor cell line. The radiolabeling yield of [^99mTc]Tc-HYNIC-FAPI was (97.29 ± 0.46) %. The radiochemical purity was more than 90% and kept stable until 6 h. The radioligand was shown as lower lipophilicity, of which logD7.4 value was − 2.38 $$\pm$$± 0.13. In vitro experiments, the results indicated that the probe showed binding properties, and inhibited the migration of tumor cells. The novel [^99mTc]Tc-HYNIC-FAPI probe was successfully radiosynthesized and exhibited good radiochemical purity, stability and in vitro binding ability to tumor cells. The [^99mTc]Tc-HYNIC-FAPI will be a promising SPECT/CT imaging probe.

Purpose of the report: To explore the value of ¹⁸F-labeled prostate-specific membrane antigen (PSMA-1007) positron emission tomography (PET)/computed tomography (CT), the maximum standardized uptake value (SUVmax) of the primary tumor, prostate PSMA-tumor volume (PSMA-TVp), and prostate total lesion PSMA (TL-PSMAp) for predicting prostate cancer (PCa) metastasis and follow-up evaluation in primary PCa lesions.Materials and methods: ¹⁸F-PSMA-1007 PET/CT data of 110 consecutive newly diagnosed PCa patients were retrospectively analyzed. Patients were divided into non-metastatic, oligometastatic, and extensive metastatic groups. The predictive power was assessed using the receiver operating characteristic curve. Multi-group one-way analysis of variance and post-hoc tests were used to compare the groups. Patients were monitored post-therapy to evaluate treatment effectiveness.Results: Among the 110 patients, 66.4% (73) had metastasis (29 oligometastatic, 44 extensive metastasis). AUCs for Gleason score (GS), total prostate-specific antigen(TPSA), SUVmax, TL-PSMAp, and PSMA-TVp were 0.851, 0.916, 0.834, 0.938, and 0.923, respectively. GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp were significantly different among the groups. In the post-hoc tests, differences in GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp between the non-metastatic and oligometastatic groups and non-metastatic and extensive metastatic groups were significant (P<0.010). Differences in TL-PSMAp and PSMA-TVp between oligometastatic and extensive metastatic groups were significant (P=0.039 and 0.015, respectively), while those among GS, TPSA, and SUVmax were not. TL-PSMAp and PSMA-TVp distinguished between oligometastatic and extensive metastases, but GS, TPSA, and SUVmax did not. In individuals with oligometastasis, the implementation of active treatment for both primary and metastatic lesions may result in a more favorable prognosis.Conclusions: ¹⁸F-PSMA-1007 PET/CT volumetric parameters PSMA-TVp and TL-PSMAp can predict PCa oligometastasis.