Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

Theranostic Agent Targeting Bone Metastasis: A Novel [68Ga]Ga/[177Lu]Lu-DOTA-HBED-bisphosphonate.

Bone metastasis in cancer patients is a major disease advancement for various types of cancer. Previously, [68Ga]Ga-HBED-CC-bisphosphonate ([68Ga]Ga-P15-041) showed excellent bone uptake and efficient detection of bone metastasis in patients. To accommodate different α- or ß--emitting metals for radionuclide therapy, a novel DOTA-HBED-CC-bisphosphonate (P15-073, 1) was prepared and the corresponding [68Ga]Ga-1 and [177Lu]Lu-1 were successfully synthesized in high yields and purity. Gallium-68 conjugation to HBED-CC at room temperature and lutetium-177 conjugation to DOTA at 95 °C were verified in model compounds through secondary mass confirmation. These bisphosphonates, [68Ga]Ga-1 and [177Lu]Lu-1, displayed high binding affinity to hydroxyapatite in vitro. After an iv injection, it showed excellent uptake in the spine of normal mice, and micro-PET/CT imaging of nude mice model of bone metastasis showed high bone uptake in tumor tissue. The results indicated that [68Ga]Ga/[177Lu]Lu-1 holds promise as a theranostic radioligand agent for managing cancer bone metastases.

18F-Labeled PET Tracers Specific for Adenosine A2A Receptor: Design, Synthesis, and Biological Evaluation.

By modifying the structures of targeted A2AR antagonists and tracers, novel compounds 3, 7a, 9, 12c, and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3, 12c, and BIBD-399 have high affinity for A2AR. [18F]3 and [18F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [18F]MNI-444 exhibits greater than that of [18F]3 and [18F]BIBD-399. PET imaging shows that [18F]3 is off-target in the brain, while [18F]BIBD-399 and [18F]MNI-444 can be specifically imaged in regions with high A2AR expression. Differently, [18F]BIBD-399 could quickly reach equilibrium in the targeted region within 10 min after administration, while [18F]MNI-444 shows a slowly increasing trend within 2 h of administration. [18F]BIBD-399 is mainly metabolized by the liver and kidney, and there is no obvious defluorination in vivo. Additional in vitro autoradiography showed that the striatal signals of [18F]BIBD-399 and [18F]MNI-444 were inhibited by the A2AR antagonist SCH442416 but not by the A1R antagonist DPCPX, demonstrating the high A2AR binding specificity of [18F]BIBD-399. Molecular docking further confirms the high affinity of MNI-444 and BIBD-399 for A2AR. Further tMCAo imaging showed that [18F]BIBD-399 can sensitively distinguish between infarcted and noninfarcted sides, a capability not observed with [18F]MNI-444. Given its pharmacokinetic properties and the ability to identify lesion regions, [18F]BIBD-399 has potential advantages in monitoring A2AR changes, meriting further clinical investigation.

Design of Novel 18F-Labeled Amino Acid Tracers Using Sulfur 18F-Fluoride Exchange Click Chemistry.

[18F]Gln-OSO2F, [18F]Arg-OSO2F, and [18F]FSY-OSO2F were designed by introducing sulfonyl 18F-fluoride onto glutamine, arginine, and tyrosine, respectively. [18F]FSY-OSO2F can be prepared directly by sulfur 18F-fluoride exchange, while [18F]Gln-OSO2F and [18F]Arg-OSO2F require a two-step labeling method. Those tracers retain their typical transport characteristics for unmodified amino acids. Both PET imaging and biodistribution confirmed that [18F]FSY-OSO2F visualized MCF-7 and 22Rv1 subcutaneous tumors with high contrast, and its tumor-to-muscle ratio was better than that of [18F]FET. However, [18F]Gln-OSO2F and [18F]Arg-OSO2F poorly image MCF-7 subcutaneous tumors, possibly due to differences in the types and amounts of transporters expressed in tumors. All three tracers can visualize the U87MG glioma. According to our biological evaluation, none of the tracers evaluated in this study exhibited obvious defluorination, and subtle structural changes led to different imaging characteristics, indicating that the application of sulfur 18F-fluoride exchange click chemistry in the design of radioactive sulfonyl fluoride amino acids is feasible and offers significant advantages.

Deep vein diameters and perivascular space scores are associated with deep medullary vein hypo-visibility in patients with white matter hyperintensity.

Background: Deep medullary vein (DMV) hypo-visibility is correlated with white matter hyperintensity (WMH), but the underlying causes remain unclear. This study aimed to explore the relationship between deep vein diameters and perivascular space (PVS) scores, and DMV hypo-visibility in the presence of WMH. Methods: This cross-sectional study prospectively analyzed the clinical and imaging data of 190 cerebral small vessel disease patients with WMH and 40 healthy controls from the Lishui Hospital of Traditional Chinese Medicine affiliated with Zhejiang Chinese Medical University. PVS scores ranging from 0 to 4 were determined according to the PVS counts in the basal ganglia area on T2-weighted magnetic resonance images; high-grade PVS was defined as a PVS score >1. The diameters of the deep cerebral veins, including the bilateral septal veins (SVs), thalamostriate veins (TSVs), lateral ventricular veins (LVVs), and internal cerebral veins, were measured using susceptibility weighted imaging (SWI). Left and right DMV scores, ranging from 0 to 9, were calculated based on the visibility of the DMV on SWI in the ipsilateral frontal, parietal, and occipital lobes. Results: The deep cerebral vein diameters, left and right DMV scores, and high-grade PVS differed between the healthy controls and WMH patients (P<0.05). Left DMV scores were independently associated with age {ß [95% confidence interval (CI)]: 0.050 (0.018, 0.082)}, high-grade PVS [ß (95% CI): 0.998 (0.262, 1.737)], and the diameters of the ipsilateral SVs [ß (95% CI): -1.114 (-1.754, -0.475)], SVs [ß (95% CI): -0.734 (-1.191, -0.277)], and LVVs [ß (95% CI): -0.921 (-1.567, -0.275)] [all false discovery rate (FDR)-corrected P<0.05]. Right DMV scores were independently associated with age [ß (95% CI): 0.071 (0.037, 0.105)], high-grade PVS [ß (95% CI): 0.873 (0.111, 1.635)], and the diameters of the ipsilateral SVs [ß (95% CI): -0.837 (-1.386, -0.289)], TSVs [ß (95% CI): -0.875 (-1.331, -0.419)], and LVVs [ß (95% CI): -1.813 (-2.484, -1.142)] (all FDR-corrected P<0.05). Conclusions: Decreased hypo-visibility of DMVs on SWI was associated with a higher age, the presence of high-grade PVS, and smaller diameters of the ipsilateral deep cerebral veins in individuals with WMH. Our findings provide novel insights into the probable mechanisms leading to high DMV scores.

Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer.

The role of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in colon cancer involves various tumorigenic processes and has been studied widely. However, the mechanism by which it promotes colon cancer remains unclear. Retroviral vector pSEB61 was retrofitted in established HCT116-siKCN and SW480-siKCN cells to silence KCNQ1OT1. Cellular proliferation was measured using CCK8 assay, and flow cytometry (FCM) detected cell cycle changes. RNA sequencing (RNA-Seq) analysis showed differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways. RT-qPCR, immunofluorescence, and western blotting were carried out to validate downstream gene expressions. The effects of tumorigenesis were evaluated in BALB/c nude mice by tumor xenografts. Our data revealed that the silencing of KCNQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M phase. RNA-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell cycle. RT-qPCR, immunofluorescence, and western blotting confirmed downstream CCNE2 and PCNA gene expressions. HCT116-siKCN cells significantly suppressed tumorigenesis in BALB/c nude mice. Our study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.

Design, Synthesis, and Evaluation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein for Brain Imaging.

Fibroblast activation protein (FAP) is closely related to central nervous system diseases such as stroke and brain tumors, but PET tracers that can be used for brain imaging have not been reported. Here, we designed, synthesized, and evaluated 18F-labeled UAMC1110 derivatives suitable for brain imaging targeting FAP. By substituting the F atom for the H atom on the aromatic ring of compound UAMC1110, 1a-c were designed and prepared. 1a-c were confirmed to have a high affinity for FAP through molecular docking and enzyme assay. [18F]1a-c were successfully prepared and confirmed to have high affinity. The stability in vivo indicates that no obvious metabolites of [18F]1a,b were found in the plasma 1 h after injection, which is beneficial for brain imaging. In vitro cell uptake experiments showed that [18F]1a,b and [68Ga]FAPI04 exhibited similar uptake and internalization rates. PET imaging of U87MG subcutaneous tumor showed that [18F]1a,b could penetrate the blood-brain barrier with higher uptake and longer retention time than [68Ga]FAPI04 (uptake at 62.5 min, 1.06 ± 0.23, 1.09 ± 0.25% ID/g vs 0.21 ± 0.10% ID/g, respectively). The brain-to-blood ratios of [18F]1a,b were better than [68Ga]FAPI04. Biodistribution and PET imaging showed that [18F]1a had better uptake on tumors and a higher tumor-to-muscle ratio than [18F]1b and [68Ga]FAPI04. Further imaging of U87MG intracranial glioma showed that [18F]1a outlined high-contrast gliomas in a short period of time compared to [18F]1b. Therefore, [18F]1a is expected to be useful in the diagnosis of FAP-related brain diseases.

Design, Synthesis, and Biological Evaluation of a Novel [18F]-Labeled Arginine Derivative for Tumor Imaging.

To better diagnose and treat tumors related to arginine metabolism, (2S,4S)-2-amino-4-(4-(2-(fluoro-18F)ethoxy)benzyl)-5-guanidinopentanoic acid ([18F]7) was designed and prepared by introducing [18F]fluoroethoxy benzyl on carbon-4 of arginine. [18F]7 and 7 were successfully prepared using synthesis methods similar to those used for (2S,4S)-4-[18F]FEBGln and (2S,4S)-4-FEBGln, respectively. In vitro experiments on cell transport mechanisms showed that [18F]7 was similar to (2S,4S)4-[18F]FPArg and was transported into tumor cells by cationic amino acid transporters. However, [18F]7 can also enter MCF-7 cells via ASC and ASC2 amino acid transporters. Further microPET-CT imaging showed that the initial uptake and retention properties of [18F]7 in MCF-7 subcutaneous tumors were good (2.29 ± 0.09%ID/g at 2.5 min and 1.71 ± 0.09%ID/g at 60 min after administration), without significant defluorination in vivo. However, compared to (2S,4S)4-[18F]FPArg (3.06 ± 0.59%ID/g at 60 min after administration), [18F]7 exhibited lower tumor uptake and higher nonspecific uptake. When further applied to U87MG imaging, [18F]7 can quickly visualize brain gliomas (tumor-to-brain, 1.85 at 60 min after administration). Therefore, based on the above results, [18F]7 will likely be applied for the diagnosis of arginine nutrition-deficient tumors and efficacy evaluations.

FOXA1/MND1/TKT axis regulates gastric cancer progression and oxaliplatin sensitivity via PI3K/AKT signaling pathway.

BACKGROUND: Drug resistance is a main factor affecting the chemotherapy efficacy of gastric cancer (GC), in which meiosis plays an important role. Therefore, it is urgent to explore the effect of meiosis related genes on chemotherapy resistance. METHODS: The expression of meiotic nuclear divisions 1 (MND1) in GC was detected by using TCGA and clinical specimens. In vitro and in vivo assays were used to investigate the effects of MND1. The molecular mechanism was determined using luciferase reporter assay, CO-IP and mass spectrometry (MS). RESULTS: Through bioinformatics, we found that MND1 was highly expressed in platinum-resistant samples. In vitro experiments showed that interference of MND1 significantly inhibited the progression of GC and increased the sensitivity to oxaliplatin. MND1 was significantly higher in 159 GC tissues in comparison with the matched adjacent normal tissues. In addition, overexpression of MND1 was associated with worse survival, advanced TNM stage, and lower pathological grade in patients with GC. Further investigation revealed that forkhead box protein A1 (FOXA1) directly binds to the promoter of MND1 to inhibit its transcription. CO-IP and MS assays showed that MND1 was coexpressed with transketolase (TKT). In addition,TKT activated the PI3K/AKT signaling axis and enhanced the glucose uptake and lactate production in GC cells. CONCLUSIONS: Our results confirm that FOXA1 inhibits the expression of MND1, which can directly bind to TKT to promote GC progression and reduce oxaliplatin sensitivity through the PI3K/AKT signaling pathway.

Evaluation of (2S,4S)-4-[18F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging.

Glutamine metabolism-related tracers have the potential to visualize numerous tumors because glutamine is the second largest source of energy for tumors. (2S,4S)-4-[18F]FEBGln was designed by introducing [18F]fluoroethoxy benzyl on carbon-4 of glutamine. The aim of this study was to investigate the pharmacokinetic properties and tumor positron emission tomography (PET) imaging characteristics of (2S,4S)-4-[18F]FEBGln in detail. The biodistribution results of nude mice bearing MCF-7 tumor showed that (2S,4S)-4-[18F]FEBGln had high initial tumor uptake, and a fast clearance rate, resulting in a high tumor-to-muscle ratio at 30 min postinjection. There was no obvious defluorination in vivo. The micro-PET-CT imaging results of (2S,4S)-4-[18F]FEBGln orthotopic MCF-7 tumor-bearing nude mice were consistent with the biological distribution results. Compared with (2S,4R)-4-[18F]FGln, (2S,4S)-4-[18F]FEBGln showed poor tumor retention, but its clearance in normal tissues was also fast, so it had better PET image contrast than the former. Unlike poor retention in MCF-7-bearing nude mice, (2S,4S)-4-[18F]FEBGln has good retention in NCI-h1975 and 22Rv1 tumor models. Since (2S,4S)-4-[18F]FEBGln has low uptake in normal lungs and high uptake in the bladder, it is expected to be used in the accurate diagnosis of lung cancer but cannot accurately determine prostate cancer. Consistent with the advantages of radiolabeled amino acids in the application of brain tumors, (2S,4S)-4-[18F]FEBGln accurately diagnoses U87MG glioma with higher contrast than [18F]FET and [18F]FDG, and there is a correlation between (2S,4S)-4-[18F]FEBGln uptake and tumor growth cycle. Further kinetic model analysis showed that (2S,4S)-4-[18F]FEBGln was similar to (2S,4R)-4-[18F]FGln, conforming to the one-compartment model and the Logan graphical model, and was expected to assess the size of the glutamine pool of the tumor. Therefore, (2S,4S)-4-[18F]FEBGln is expected to provide a strong imaging basis for the diagnosis, formulation of personalized plans, and efficacy evaluation of glioma, lung cancer, and breast cancer.

Synthesis and In Vitro and In Vivo Evaluation of 18F-Labeled Positron Emission Tomography Tracers for Imaging Aß Plaques.

Accurate quantification of amyloid beta (Aß) plaques is an important indicator for Alzheimer's disease diagnosis and treatment. For this purpose, new highly sensitive Aß tracers were designed by regulating the position and number of nitrogen atoms. A series of derivatives of florbetapir (AV45) containing different numbers and positions of N atoms were synthesized and evaluated for in vitro affinity and in vivo biodistribution. Preliminary study results showed that [18F]BIBD-124 and [18F]BIBD-127 had better clearance rates and less in vivo defluorination than AV45 in ICR (ICR = Institute of Cancer Research) mice. Autoradiography and molecular docking indicated that the binding sites of [18F]BIBD-124/127 were similar to that of [18F]AV45. Micro-positron emission tomography-computed tomography imaging further demonstrated that [18F]BIBD-124 could monitor Aß plaques similar to [18F]AV45. Besides, the imaging contrast of [18F]BIBD-124 is better than that of [18F]AV45. Mass spectrometric metabolic analysis showed that BIBD-124 was less demethylated than AV45 without subsequent acetylation, which might explain its less non-specific uptake and higher imaging contrast. Gauss calculations further confirmed that the introduction of N5 in [18F]BIBD-124 decreased demethylation. Considering imaging contrast and in vivo defluorination, [18F]BIBD-124 is expected to be a promising radiotracer of Aß plaques for further clinical trials.

Optimization of Precursor Synthesis Conditions of (2S,4S)4-[18F]FPArg and Its Application in Glioma Imaging.

Although the tracer (2S,4S)4-[18F]FPArg is expected to provide a powerful imaging method for the diagnosis and treatment of clinical tumors, it has not been realized due to the low yield of chemical synthesis and radiolabeling. A simple synthetic method for the radiolabeled precursor of (2S,4S)4-[18F]FPArg in stable yield was obtained by adjusting the sequence of the synthetic steps. Furthermore, the biodistribution experiments confirmed that (2S,4S)4-[18F]FPArg could be cleared out quickly in wild type mouse. Cell uptake experiments and U87MG tumor mouse microPET-CT imaging experiments showed that the tumor had high uptake of (2S,4S)4-[18F]FPArg and the clearance was slow, but (2S,4S)4-[18F]FPArg was rapidly cleared in normal brain tissue. MicroPET-CT imaging of nude mice bearing orthotopic HS683-Luc showed that (2S,4S)4-[18F]FPArg can penetrate blood-brain barrier and image gliomas with a high contrast. Therefore, (2S,4S)4-[18F]FPArg is expected to be further applied in the diagnosis and efficacy evaluation of clinical glioma.

[18F]BIBD-239: 18F-Labeled ER176, a Positron Emission Tomography Tracer Specific for the Translocator Protein.

[11C]ER176 has adequate sensitivity to image the human brain translocator protein (TSPO) in all three genotypes by positron emission tomography (PET). However, its clinical application is limited by the short half-life of 11C (20.38 min). To overcome the deficiency of [11C]ER176 and keep the pharmacophore features of ER176 to the maximum extent, we designed four fluorine-labeled ER176 derivatives using the deuterium method. In vitro competition binding confirmed that the designed compounds had high affinity for TSPO. Biodistribution experiments showed that tissues with high expression of TSPO had high uptake of these compounds, as well as that the compound showed high brain penetration and mild defluorination in vivo. Therefore, [18F]BIBD-239 with simple synthesis conditions was selected for further biological evaluation. Theoretical simulations showed that BIBD-239 and ER176 have similar binding modes and sites to Ala147-TSPO and Thr147-TSPO, which indicated that the tracers may have consistent sensitivity to the three affinity genotypes. In vitro autoradiography and in vivo PET studies of the ischemic rat brain showed dramatically higher uptake of [18F]BIBD-239 on the lesion site compared to the contralateral side with good brain kinetics. Additionally, [18F]BIBD-239 provided clear tumor PET images in a GL261 glioma model. Importantly, PET imaging and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) results showed that in vivo defluorination and other metabolites of [18F]BIBD-239 did not interfere with brain imaging. Conclusively, [18F]BIBD-239, similar to ER176 with low polymorphism sensitivity, has simple labeling conditions, high labeling yield, high affinity, and high specificity for TSPO, and it is planned for further evaluation in higher species.

A modified method for Billroth-II gastrojejunostomy after laparoscopy-assisted distal gastrectomy.

Background: There are many types of gastrojejunostomy reconstruction after laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer, each of which has merits and demerits. This study introduced a novel method (called pant-shaped anastomosis) involving the construction of a side-to-side anastomosis between the afferent loop and efferent loop at the site of gastrojejunal anastomosis using a linear stapler. The results of applying pant-shaped anastomosis to LADG were also analyzed. Methods: The clinical data of 96 patients who underwent LADG with pant-shaped anastomosis between June 2018 and June 2020 at The First Affiliated Hospital of Wannan Medical College (Wuhu City, China) were analyzed retrospectively. Results: All procedures were successfully completed without conversion to open laparotomy. An average pant-shaped anastomosis took 22 min to construct and had a mean incision length of 5.3 cm. The mean time to postoperative first flatus was 3.5 days. The mean time to intake of an oral semiliquid diet was 5.5 days. The average postoperative hospital stay was 8.2 days. No patient developed extraluminal bleeding, intraluminal bleeding, anastomosis leakage, afferent obstruction, internal herniation or pancreatitis. The proportion of patients who experienced significant reflux was 10.1% (Visick III-IV). In total, 62.6% of patients exhibited endoscopic reflux gastritis of grade 1 or less. Conclusions: Pant-shaped anastomosis is a safe and simple procedure. It is a feasible option to reduce afferent obstruction after LADG in patients with distal gastric cancer.

Novel 18F-Labeled PET Tracers Specific to Aromatase: Design, Synthesis, and Biological Evaluation.

The abnormal expression of aromatase is associated with the occurrence and development of a variety of neurological diseases and tumors. A series of 18F-labeled and 68Ga-labeled potential aromatase-binding candidate compounds were designed and synthesized based on the structures of aromatase inhibitors. Competitive inhibition experiments in vitro and molecular docking showed that BIBD-069 and BIBD-071 have high affinity for aromatase. The radiolabeling conditions of [18F]BIBD-069 and [18F]BIBD-071 were simple, and the yields were high. Biodistribution and in vivo inhibition experiments confirmed that [18F]BIBD-069 and [18F]BIBD-071 specifically bind to aromatase. [18F]BIBD-069 and [18F]BIBD-071 selectively imaged the amygdala and nucleus of the stria terminalis, which is similar to the imaging result of [11C]vorozole. Radiometabolites of [18F]BIBD-069 and [18F]BIBD-071 did not bind to aromatase and interfered with brain imaging. MicroPET-CT imaging further confirmed that [18F]BIBD-069 and [18F]BIBD-071 can specifically bind to aromatase and were not defluorinated in vivo. Given that [18F]BIBD-069 and [18F]BIBD-071 exhibit excellent aromatase binding affinities, mild radiolabeling conditions, and good pharmacokinetics, they can be important tools for the diagnosis and treatment of aromatase-related diseases.

[18F]BIBD-181: A Novel Positron Emission Tomography Tracer Specific for Synaptic Vesicle Glycoprotein 2A.

Dysfunction or decreased expression of synaptic vesicle glycoprotein 2A (SV2A) is closely related to the progression of neurodegenerative diseases and psychiatric disorders. The development of positron emission tomography (PET) tracers targeting SV2A can provide a strong imaging basis for the diagnosis and treatment of these diseases. Herein we report the synthesis of the novel radiotracer [18F]BIBD-181 and its preclinical evaluation. The absolute configuration of BIBD-181 was confirmed by the single-crystal structure of its precursor. The in vitro binding assay of BIBD-181 showed high SV2A binding affinity. Compared with previously reported tracers, [18F]BIBD-181 has mild labeling conditions, simple operation, and high yield. The in vivo metabolism of [18F]BIBD-181 is similar to that of UCB derivatives, and the metabolites do not interfere with brain PET imaging. Biodistribution and PET studies showed that [18F]BIBD-181 has high brain uptake and good pharmacokinetics. Autoradiography and PET inhibition studies indicated that [18F]BIBD-181 specifically binds SV2A. Because [18F]BIBD-181 exhibits excellent properties, it may be a reliable probe of quantities for SV2A-related disease diagnosis.

Is Natural Orifice Specimen Extraction Surgery Really Safe in Radical Surgery for Colorectal Cancer?

Background: The main feature of natural orifice specimen extraction (NOSE) is its avoidance of an auxiliary abdominal incision. The safety of NOSE remains controversial. This study aimed to investigate the early safety of transanal NOSE in the treatment of sigmoid colon and upper rectal cancer from the follow aspects: clinical and pathological characteristics, inflammatory and immune indicators and postoperative complications. Methods: Data from 125 patients diagnosed with sigmoid colon, and upper rectal cancer by gastrointestinal surgery in the First Affiliated Hospital of Wannan Medical College from January 2017 to June 2020 were analyzed. Patients were assigned to two surgical groups: Conventional laparoscopic-assisted radical resection for CRC (CLA, 75cases) and laparoscopic-assisted radical resection for CRC with NOSE (La-NOSE, 50 cases). The following were compared: clinical and pathological characteristics; intraoperative, bacteriological, and oncological results; postoperative inflammation and immune response indexes. Bacteriological results were obtained by aerobic and anaerobic bacterial culture of peritoneal wash fluid and oncology results by cytological analysis of peritoneal wash liquid exudation. Inflammation indicators included postoperative C-reactive protein (CRP) and procalcitonin (PCT) trend reactions. The immune index was the level of postoperative T lymphocytes (CD3, CD4/CD8). All data were analyzed by using SPSS statistical version 18.0 for windows. Measurement data are presented as the means ± standard deviations, and two-group comparisons were performed using the t-test. Comparisons of count data were performed using the chi-square test. p <0.05 indicates that the difference was statistically significant. Results: The bacterial culture positive rate was not significant in the La-NOSE group (15/50 vs 19/75) than in the CLA group. The exfoliative cytology (EC) rate of the peritoneal wash fluid was 0 in both groups.The La-NOSE group had a significantly higher postoperative day 2(POD2) CRP and PCT level than the CLA group. The POD2 CD3 and CD4/CD8 levels were higher in the La-NOSE group than in the CLA group. There was no significant difference in the incidence of postoperative complications between the two groups (La-NOSE group vs CLA group: 3/50 vs 6/75) (p>0.05). Conclusions: Although the incidence of intra-abdominal contamination is high, it does not develop into a severe infectious disease, and does not lead to the implantation of free tumor cells into the abdominal cavity. Therefore, it is safe for the NOSE to treat colorectal cancer.

A Modified Anastomosis Technique for Esophagojejunostomy after Laparoscopy-Assisted Total Gastrectomy: A Single Team Preliminary Experience.

RESULTS: There were no significant differences between the cRY group and pRY group regarding age, sex, BMI, neoadjuvant therapy, preoperative comorbidities, history of laparotomy, ASA score, tumor location, pathological stage, total operative time, incision length, blood loss, time-to-first flatus, time-to-first soft diet, and postoperative hospital stays. The proportions of patients who received a 21 mm stapler were higher in the cRY group (7/44) than that in the pRY group (0/68) (P = 0.003). 7 anastomotic complications were reported (6 in the cRY group versus 1 in pRY group; P = 0.028) of which five (83.3%) in the cRY were anastomotic stenosis versus none in the pRY group (P = 0.044). CONCLUSIONS: The application of pant-shaped anastomosis for esophagojejunostomy after LTG is a safe and feasible procedure and has an advantage when the jejunum diameter is small.