The Application of 18 F-FES PET in Clinical Cancer Care : A Systematic Review.

INTRODUCTION: [ 18 F]fluoroestradiol (FES) can be used for the noninvasive visualization and quantification of tumor estrogen receptor (ER) expression and activity and was FDA-approved as a diagnostic agent in May 2022 for detecting ER-positive lesions in patients with recurrent or metastatic breast cancer. PET imaging was also used to detect ER-positive lesions and malignancy among patients with uterine, ovarian, and other ER-positive solid tumors. We conducted a systemic review of the studies on FES PET imaging used among patients with cancer not limited to breast cancer to better understand the application of FES PET imaging. METHODS: PubMed/MEDLINE and Cochrane Library databases were used to perform a comprehensive and systematic search and were updated until August 15, 2022. Two authors independently reviewed the titles and abstracts of the retrieved articles by using the search algorithm and selected the articles based on the inclusion and exclusion criteria. All statistical analyses were conducted using R statistical software. RESULTS: Forty-three studies with 2352 patients were included in the qualitative synthesis, and 23 studies with 1388 patients were included in the quantitative analysis, which estimated the FES-positive detection rate. Thirty-two studies (77%) included breast cancer patients in 43 included studies. The FES SUV mean was higher in patients with endometrial cancer (3.4-5.3) than in those with breast cancer (2.05) and uterine sarcoma (1.1-2.6). The pooled detection rates of FES PET imaging were 0.80 for breast and 0.84 for ovarian cancer patients, both similar to that of 18 F-FDG. The FES uptake threshold of 1.1 to 1.82 could detect 11.1% to 45% ER heterogeneity, but the threshold of FES uptake did not have consistent predictive ability for prognosis among patients with breast cancer, unlike uterine cancer. However, FES uptake can effectively predict and monitor treatment response, especially endocrine therapy such as estradiol, ER-blocking agents (fulvestrant and tamifoxen), and aromatase inhibitors (such as letrozole and Z-endoxifen). CONCLUSIONS: [ 18 F]fluoroestradiol PET is not only a convenient and accurate diagnostic imaging tool for detecting ER-expressing lesions in patients with breast and ovarian cancer but also among patients with uterine cancer. [ 18 F]fluoroestradiol PET is a noninvasive predictive and monitoring tool for treatment response and prognosis.

Comparing the Detection Performance Between Multiparametric Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen PET/CT in Patients With Localized Prostate Cancer: A Systematic Review and Meta-analysis.

PURPOSE: Multiparametric MRI (mpMRI) has been promoted as an auxiliary diagnostic tool for prostate biopsy. However, prostate-specific membrane antigen (PSMA) including 68 Ga-PSMA-11, 18 F-DCFPyL, and 18 F-PSMA-1007 applied PET/CT imaging was an emerging diagnostic tool in prostate cancer patients for staging or posttreatment follow-up, even early detecting. Many studies have used PSMA PET for comparison with mpMRI to test the diagnostic ability for early prostate cancer. Unfortunately, these studies have shown conflicting results. This meta-analysis aimed to compare the differences in diagnostic performance between PSMA PET and mpMRI for detecting and T staging localized prostatic tumors. METHODS: This meta-analysis involved a systematic literature search of PubMed/MEDLINE and Cochrane Library databases. The pooling sensitivity and specificity of PSMA and mpMRI verified by pathological analysis were calculated and used to compare the differences between the 2 imaging tools. RESULTS: Overall, 39 studies were included (3630 patients in total) from 2016 to 2022 in the current meta-analysis and found that the pooling sensitivity values for localized prostatic tumors and T staging T3a and T3b of PSMA PET were 0.84 (95% confidence interval [CI], 0.83-0.86), 0.61 (95% CI, 0.39-0.79), and 0.62 (95% CI, 0.46-0.76), respectively, whereas those of mpMRI were found to be 0.84 (95% 0.78-0.89), 0.67 (95% CI, 0.52-0.80), and 0.60 (95% CI, 0.45-0.73), respectively, without significant differences ( P > 0.05). However, in a subgroup analysis of radiotracer, the pooling sensitivity of 18 F-DCFPyL PET was higher than mpMRI (relative risk, 1.10; 95% CI, 1.03-1.17; P < 0.01). CONCLUSIONS: This meta-analysis found that whereas 18 F-DCFPyL PET was superior to mpMRI at detecting localized prostatic tumors, the detection performance of PSMA PET for localized prostatic tumors and T staging was comparable to that of mpMRI.

New Rosane Diterpenoids and Their Analogs from Euphorbia ebracteolata Hayata.

Phytochemical investigation of the roots of Euphorbia ebracteolata Hayata resulted in the isolation of three new rosane diterpenoids, euphebracteolatins C-E (1-3), along with fourteen known analogs (4-17). Their structures were determined on the basis of extensive spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR. Euphebracteolatin C (1) contains a C-1/C-10 double bond and a keto group at C-7, and euphebracteolatins D and E (2-3) possess an aromatic ring-A in their skeleton. The plausible biogenetic pathways of all the isolates were also proposed. Furthermore, compounds 1 and 9 showed selective cytotoxicity against HepG2 cells with IC50 values of 14.29 and 12.33 µM, respectively, and 2-3 displayed moderate cytotoxicity against three human cancer lines, with IC50 values ranging from 23.69 to 39.25 µM.

Comparison of the Detection Performance Between FAP and FDG PET/CT in Various Cancers: A Systemic Review and Meta-analysis.

PURPOSE: 18F-FDG is the dominant radiotracer in oncology; however, it has limitations. Novel labeled fibroblast activation protein (FAP) radiotracers have been developed and published in several studies. Thus, this meta-analysis aimed to compare the detection rates (DRs) of FDG and FAP, based on previous studies from a systematic review. METHODS: PubMed/MEDLINE and Cochrane library databases were used to perform a comprehensive and systematic search and are updated to April 30, 2022. The DR, relative risk, and the SUVmax were calculated between the FAP and FDG tracers. Finally, the sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve of FAP and FDG were analyzed using gold and reference standards. RESULTS: Thirty studies (1170 patients) were included in the meta-analysis. The relative risks of FAP DR for the primary tumor, recurrent tumor, lymph node metastasis, and distant metastasis were FDG 1.06- to 3.00-fold per patient and per lesion. For the primary tumor, FAP uptake was most intense in pancreatic cancer, followed by head and neck, cervical, colorectal, lung, gastric, and hepatocellular carcinoma, and was higher than FDG except for urological system cancer. The sensitivity (0.84-0.98), diagnostic odds ratio (19.36-358.47), and summary receiver operating characteristic curve (0.94-0.99) of FAP based on patient and lesion were better for primary tumors, LN metastasis, and distant metastasis than FDG. CONCLUSIONS: Fibroblast activation protein is an extremely potential radiotracer to replace most of the use of FDG in oncology. It is noteworthy that the FAP tracers for primary tumors had low specificity despite excellent sensitivity and had lower uptake than FDG in urological system cancer. In addition, the difference in detection between FAP and FDG for LN metastasis could not be certain in sarcoma.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

BACKGROUND: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. MAIN BODY: This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. CONCLUSION: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry.

Jolkinolide B: A comprehensive review of its physicochemical properties, analytical methods, synthesis and pharmacological activity.

Jolkinolide B is a typical ent-abietane-type diterpenoid, which is first found in Euphorbia jolkini. It is one of the most important active components in many toxic Euphorbia plants. In recent years, jolkinolide B has garnered increasing attention due to its high potent and multiple pharmacological activities. In order to better understand the research status of jolkinolide B, relevant information about jolkinolide B was collected from scientific databases (SciFinder Scholar, PubMed, ACS website, Elsevier, Web of Science, Google Scholar, Science Direct, and CNKI). There are few studies on chemical synthesis and biosynthesis of jolkinolide B. In addition, researchers on the activities of jolkinolide B are mostly concentrated at the cellular level, and there is a lack of research on the mechanism. In this review, the possible applications of jolkinolide B were systematically illustrated for the first time, from plant sources, physicochemical properties, analytical methods, synthesis and pharmacological activities. Jolkinolide B exhibits extensive pharmacological properties, including anticancer, anti-inflammatory, anti-osteoporosis, and anti-tuberculosis activities. Pharmacological activities of jolkinolide B were mainly focused on anticancer and anti-inflammatory activities, and the mechanism of action may be related with inhibition of JAK/STAT pathway, NF-κB pathway and PI3K/Akt/mTOR pathway. In addition, the extraction methods and analytical methods discussed in this review, will facilitate the development of novel herbal products for better healthcare solutions.

Neuroinflammation in Low-Level PM2.5-Exposed Rats Illustrated by PET via an Improved Automated Produced [18F]FEPPA: A Feasibility Study.

Background: [18F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats. Results: Using this automated synthesis method, the RCY of the [18F]FEPPA was 38 ± 4% (n = 17, EOB) in a synthesis time of 83 ± 8 min from EOB. The radiochemical purity and molar activities were greater than 99% and 209 ± 138 GBq/µmol (EOS, n = 15), respectively. The quality of the [18F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]FEPPA was stable at 21 ± 2°C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [18F]FEPPA in the brain of PM2.5-exposed rats (n = 6) were higher than that of normal controls (n = 6) and regional-specific. Conclusions: Using the improved semipreparative HPLC purification, [18F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons.

The Detection Performance of 18 F-Prostate-Specific Membrane Antigen-1007 PET/CT in Primary Prostate Cancer : A Systemic Review and Meta-analysis.

BACKGROUND: Multiple tools are now available to determine the requirement for a biopsy to diagnose prostate cancer, and PET/CT with radiolabeled prostate-specific membrane antigen (PSMA)-targeting radiotracers has been recommended for detecting primary prostate cancer. Particularly, the radiotracer 18 F-PSMA-1007 was found to be more favorable for primary tumors compared with other PSMA-targeting radiotracers because of its low clearance via the urinary tract and better image resolution. Thus, we performed a systematic review and meta-analysis to more accurately evaluate the detection performance of 18 F-PSMA-1007 PET/CT in primary prostate cancer patients. METHODS: An update on the databases of PubMed/MEDLINE, EMBASE, and Cochrane Library for comprehensive literature search was performed on September 30, 2021. The pooling detection rate was calculated on a per-patient basis. The pooling median of the SUV max was analyzed from the included studies. Furthermore, the positive predictive value of 18 F-PSMA-1007 PET/CT with pathologic lesions was analyzed using the criterion standard. RESULTS: Twelve studies (540 patients total) were included in the meta-analysis. The overall pooling detection rate of 18 F-PSMA-1007 per patient was 94%, and the pooling median of SUV max located at the intraprostate tumor was 16 (range, 3.7-77.7). The positive predictive value of 18 F-PSMA-1007 per lesion with histopathological validation was 0.90, detecting regional lymph node metastasis was 0.94, and detecting localized prostatic tumors was 0.84. CONCLUSIONS: In the current meta-analysis, we revealed the excellent performance of 18 F-PSMA-1007 to detect localized prostatic tumor lesions and regional lymph node metastasis. Moreover, the uptake of localized tumors in primary prostate cancer was nearly liver uptake and may be considered a suspicious malignancy if it was equal to or greater than the liver uptake.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

BACKGROUND: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development. RESULTS: This commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals and also a contribution in relation to MRI-agents is included. CONCLUSION: Trends in (radio)chemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.

Design and implementation of single disease data quality management system based on hospital information system / 中华医院管理杂志

Quality management and control of single disease is a means to continuously improve medical quality and safety by building a set of quality control indicators and evaluation systems based on the whole process of disease diagnosis and treatment. In the actual single disease management process, the reporting of each disease involved data from various systems such as electronic medical records, and the data integration was difficult. While the traditional manual reporting method took a lot of time and the data accuracy could not be guaranteed. In the development process of hospital informatization, a hospital has designed a set of intelligent full-closed loop single disease management platform based on the hospital information system, by integrating the existing human and information data resources of the hospital. This platform integrated functions of single disease intranet reporting, in-depth capture of reporting elements, single-disease quality index management, and single-disease real-time intelligent control, in order to promote more refined and intelligent disease management and thus steadily improve medical quality and safety.

GMP-compliant fully automated radiosynthesis of [18F]FEPPA for PET/MRI imaging of regional brain TSPO expression.

BACKGROUND: Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. The second-generation PET ligand [18F]FEPPA specifically binds TSPO to enable in vivo visualization and quantification of neuroinflammation. We optimized a fully automated radiosynthesis method and evaluated the utility of [18F]FEPPA, the second-generation PET ligand specifically binds TSPO, in a mouse model of systemic LPS challenge to detect TSPO-associated signals of central and peripheral inflammation. In vivo dynamic PET/MR imaging was performed in LPS-induced and control mice after [18F]FEPPA administration. The relationship between the [18F]FEPPA signal and the dose of LPS was assessed. The cytokine levels (i.e., TNF-α, Il-1ß, Il-6) in LPS-induced mice were measured by RT-PCR. Standard uptake value (SUV), total volume of distribution (VT) and area under the curve (AUC) were determined based on the metabolite-uncorrected plasma input function. Western blotting and immunostaining were used to measure TSPO expression in the brain. RESULTS: The fully automated [18F]FEPPA radiosynthesis produced an uncorrected radiochemical yield of 30 ± 2% within 80 min, with a radiochemical purity greater than 99% and specific activity of 148.9‒216.8 GBq/µmol. Significant differences were observed in the brain after [18F]FEPPA administration: SUV, VT and AUC were 1.61 ± 0.1, 1.25 ± 0.12 and 1.58 ± 0.09-fold higher in LPS-injected mice than controls. TNF-α, Il-1ß and Il-6 mRNA levels were also elevated in the brains of LPS-injected mice. Western blotting revealed TSPO (p < 0.05) and Iba-1 (p < 0.01) were upregulated in the brain after LPS administration. In LPS-injected mice, TSPO immunoactivity colocalized with Iba-1 in the cerebrum and TSPO was significantly overexpressed in the hippocampus and cerebellum. The peripheral organs (heart, lung) of LPS-injected mice had higher [18F]FEPPA signal-to-noise ratios than control mice. CONCLUSIONS: Based on the current data on ligand specificity and selectivity in central tissues using 7 T PET/MR imaging, we demonstrate that [18F]FEPPA accumulations significant increased in the specific brain regions of systemic LPS-induced neuroinflammation (5 mg/kg). Future investigations are needed to determine the sensitivity of [18F]FEPPA as a biomarker of neuroinflammation as well as the correlation between the PET signal intensity and the expression levels of TSPO.

Ethnopharmacology, phytochemistry, pharmacology, clinical applications and toxicology of the genus Stellera Linn.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Stellera Linn. consists of species of perennial herbs and shrubs, and is mainly distributed in the temperate regions of east Asia to west Asia. There are 10∼12 species in the world, two species in China: Stellera chamaejasme Linn. and Stellera formosana Hayata ex Li. As recorded, the roots of Stellera species are used to dissipate phlegm and relieve pain. The roots and the barks can be used for papermaking. AIM OF THIS REVIEW: This review aims to summarize the ethnopharmacological uses, chemical constituents, pharmacological activities, clinical applications and toxicology of the genus Stellera to better understand their therapeutic potential in the future. MATERIALS AND METHODS: The relevant information of the genus Stellera was collected from scientific databases (Pubmed, ACS website, SciFinder Scholar, Elsevier, Google Scholar, Web of Science and CNKI). Information was also gathered from 'Flora Republicae Popularis Sinicae (〈〈〉〉)', folk records, conference papers on ethnopharmacology, Ph.D. and Masters' Dissertation. RESULTS: Stellera plants have been studied as traditional folk medicines all around the world. The chemical constituents of Stellera species mainly comprise terpenoids, flavonoids, coumarins, lignans, and so on. Extracts and compounds of Stellera species exhibit extensive pharmacological activities, such as anti-tumor, anti-viral, anti-convulsive, anti-epileptic, anti-bacterial and anti-insect activities, etc. Clinical applications have suggested that the genus Stellera has the effects in treating several skin diseases and cancers, however, the results should be further verification. The genus Stellera plants are toxic and should be used reasonable. CONCLUSION: This paper reviewed the ethnopharmacological uses, chemical constituents, pharmacology, clinical applications and toxicology of the genus Stellera. The genus Stellera has broad application prospects. However, further in-depth studies are needed to determine the medical uses of the genus and its chemical constituents, pharmacological activities, clinical applications and toxicology.

Synthesis and analysis of 4-(3-fluoropropyl)-glutamic acid stereoisomers to determine the stereochemical purity of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) for clinical use.

(4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is a positron emission tomography (PET) imaging agent for measuring the system xC- transporter activity. It has been used for the detection of various cancers and metastasis in clinical trials. [18F]FSPG is also a promising diagnostic tool for evaluation of multiple sclerosis, drug resistance in chemotherapy, inflammatory brain diseases, and infectious lesions. Due to the very short half-life (110 min) of 18F nuclide, [18F]FSPG needs to be produced on a daily basis; therefore, fast and efficient synthesis and analytical methods for quality control must be established to assure the quality and safety of [18F]FSPG for clinical use. To manufacture cGMP-compliant [18F]FSPG, all four nonradioactive stereoisomers of FSPG were prepared as reference standards for analysis. (2S,4S)-1 and (2R,4R)-1 were synthesized starting from protected L- and D-glutamate derivatives in three steps, whereas (2S,4R)-1 and (2R,4S)-1 were prepared in three steps from protected (S)- and (R)-pyroglutamates. A chiral HPLC method for simultaneous determination of four FSPG stereoisomers was developed by using a 3-cm Chirex 3126 column and a MeCN/CuSO4(aq) mobile phase. In this method, (2R,4S)-1, (2S,4S)-1, (2R,4R)-1, and (2S,4R)-1 were eluted in sequence with sufficient resolution in less than 25 min without derivatization. Scale-up synthesis of intermediates for the production of [18F]FSPG in high optical purity was achieved via stereo-selective synthesis or resolution by recrystallization. The enantiomeric excess of intermediates was determined by HPLC using a Chiralcel OD column and monitored at 220 nm. The nonradioactive precursor with >98% ee can be readily distributed to other facilities for the production of [18F]FSPG. Based on the above accomplishments, cGMP-compliant [18F]FSPG met the acceptance criteria in specifications and was successfully manufactured for human use. It has been routinely prepared and used in several pancreatic ductal adenocarcinoma metastasis-related clinical trials.

Three-step two-pot automated production of NCA [18F]FDOPA with FlexLab module.

Automated three-step two-pot production of no-carrier-added (NCA) [18F]FDOPA was first implemented in the iPHASE FlexLab module. Decay-corrected radiochemical yield (RCY) of [18F]FDOPA synthesized by this method was 10~14% (n = 7) with a synthesis time of ~110 min [18F]FDOPA was obtained in > 95% of radiochemical purity with a molar activity of ~431 GBq/µmol. With the method successfully implementing on the commercial FlexLab module and its built-in step-by-step activity monitoring, further processes optimization would be achieved.

Synthesis and evaluation of 2-(2'-((dimethylamino)methyl)-4'-(2-fluoroethoxy-substituted)phenylthio)benzenamine derivatives as potential positron emission tomography imaging agents for serotonin transporters.

A series of diphenylsulfide derivatives with various substitutions at the 4-position on phenyl ring A and different lengths of the 2-fluoroethoxy-substituted side-chain at the 4'-position on ring B were synthesized and evaluated as potential positron emission tomography (PET) imaging agents for serotonin transporters (SERT). These ligands exhibited high SERT binding affinities (Ki = 0.11-1.3 nM) and the 4-methyl-substituted (4-Me) compounds 7a and 8a displayed excellent selectivity for SERT versus norepinephrine transporters (NET) (392- and 700-fold, respectively). In the parallel artificial membrane permeability assay (PAMPA), these ligands demonstrated moderate to high brain penetration, and the 4-Me analogs showed higher BBB permeability than the corresponding 4-F analogs. The 2-fluoroethoxy-substituted ligands showed higher metabolic stability and lower lipophilicity than 4-F-ADAM. [18F]7a-c were readily prepared using an automatic synthesizer and exhibited significant uptake and slow washout in rat brains. At 120 min after iv injection, [18F]7a exhibited the highest uptake in the midbrain, whereas [18F]7b exhibited the highest uptake in the hypothalamus and midbrain. After treatment with citalopram, a SERT-selective ligand, the uptake of [18F]7a in the hypothalamus and striatum was significantly decreased. The potent and highly selective SERT binding and the selective and reversible accumulation in SERT-rich brain regions suggested that [18F]7a is a promising lead for the further development of novel [18F]-labeled PET imaging agents for SERT binding sites in the brain.

RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. @*Materials and Methods@#We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. @*Results@#Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. @*Conclusion@#RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.

Evaluation of red blood cell distribution width and platelet distribution width in combination with Glasgow Coma Score for the prognosis of patients with severe traumatic brain injury / 医学研究生学报

ObjectiveAt present, there are few studies on prognostic indicators for patients with severe traumatic brain injury (STBI). This paper aims to explore its significance by analyzing the demographic characteristics of patients with STBI, as well as parameters such as clinical laboratory test indicators.MethodsA retrospective analysis was performed on 139 STBI patients admitted to the Department of Emergency Medicine, General Hospital of Eastern Theater Command from January 2017 to December 2018. According to the 28-day death event, the participants were divided into the survival group (n=108) and the death group (n=31). Indicators such as Glasgow Coma Score (GCS), red blood cell distribution width (RDW), platelet distribution width (PDW) and clot-related indicators were collected. Univariate and multivariate logistic regression were used to analyze the risk factors related to death, and receiver operating characteristic (ROC) curve was adopted to determine their prognostic values.ResultsThere were significant differences in GCS, RDW and PDW between the two groups. RDW (OR=4.577, 95% CI: 1.704-12.291), PDW (OR=1.346, 95% CI: 1.093-1.657) and GCS (OR=0.469, 95% CI: 0.301-0.730) were risk factors for death of STBI patients. The area under the curve (AUC) of RDW, PDW and GCS scores were 0.735 (0.640-0.840), 0.675 (0.553-0.796) and 0.737 (0.638-0.837), respectively, and the AUC of the combination of the three was 0.840 (0.748-0.932), which was significantly better than that of single diagnosis.ConclusionRDW, PDW combined with GCS can effectively evaluate the prognosis of patients with STBI, which has important guiding value for clinicians′ diagnosis and treatment.

An one-pot two-step automated synthesis of [18F]T807 injection, its biodistribution in mice and monkeys, and a preliminary study in humans.

[18F]T807 is a potent tau protein imaging agent. In order to fulfill the demand from preclinical and clinical studies, we developed an automated one-pot two-step synthesis of this potent tau imaging agent and studied its stability, and dosimetry in mice and monkeys. We also conducted a preliminary study of this imaging agent in humans. Using this one-pot two-step method, the radiochemical yield (RCY) of [18F]T807 was 20.5 ± 6.1% (n = 15) at the end of bombardment (EOB) in a synthesis time of 70±5 min. The chemical and radiochemical purities were >90% and the specific activities were 151 ± 52 GBq/µmol. The quality of [18F]T807 synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]T807 injection was stable at room temperature for up to 4 h after the end of synthesis (EOS). The estimated effective dose of the [18F]T807 injection extrapolated from monkeys was 19 µSv/MBq (n = 2), while the estimated effective doses of the [18F]T807 injection extrapolated from fasted and non-fasted mice were 123 ± 27 (n = 3) and 94 ± 19 (n = 4) µSv/MBq, respectively. This one-pot two-step automated method produced the [18F]T807 injection with high reproducibility and high quality. PET imaging and radiation dosimetry evaluation in mice and Formosan rock monkeys suggested that the [18F]T807 injection synthesized by this method is suitable for use in human PET imaging studies. Thus, this method could fulfill the demand for the [18F]T807 injection in both preclinical and clinical studies of tauopathies, especially for nearby study sites without cyclotrons.

Evaluation of 5-[18F]fluoro-2'-deoxycytidine as a tumor imaging agent: A comparison of [18F]FdUrd, [18F]FLT and [18F]FDG.

One of the hallmarks of cancer is increased cell proliferation. Measurements of cell proliferation by estimation of DNA synthesis with several radiolabeled nucleosides have been tested to assess tumor growth. Deoxycytidine can be phosphorylated by deoxycytidine kinase (dCK) and is incorporated into DNA. This study evaluated a radiofluorinated deoxycytidine analog, 5-[18F]fluoro-2'-deoxycytidine ([18F]FdCyd), as a proliferation probe and compared it with 5-[18F]fluoro-2'-deoxyuridine ([18F]FdUrd), 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), and [18F]fluorodeoxyglucose ([18F]FDG) in a tumor-bearing mouse model. [18F]FdCyd was synthesized from two precursors by direct electrophilic substitution. The serum stability and partition coefficient of [18F]FdCyd were evaluated in vitro. Positron emission topography (PET) imaging of Lewis lung carcinoma (LLC)-bearing mice with [18F]FdCyd, [18F]FdUrd, [18F]FLT, and [18F]FDG were evaluated. [18F]FdCyd was stable in mouse serum and normal saline for up to 4 h. With all radiotracers except [18F]FLT, PET can clearly delineate the tumor lesion. [18F]FdCyd and [18F]FdUrd showed high accumulation in the liver and kidney. The SUV and tumor-to-muscle (T/M) ratios derived from PET imaging of the radiotracers were [18F]FDG > [18F]FdCyd > [18F]FdUrd > [18F]FLT. Selective retention in tumors with a favorable tumor/muscle ratio makes [18F]FdCyd a protential candidate for further investigation as a proliferation imaging agent.