Small animal PET is a quantitative imaging technique that can noninvasive and dynamically image the distribution of positron-labeled radiopharmaceuticals in vivo,therefore representing a new means of providing information for drug development and evaluation.This article reviews the fundamental basis of PET imaging and their application in preclinical drug discovery and development.

Objective To evaluate the effectiveness and safety of higenamine (HG),a pharmaco logical stress agent,for the detection of myocardial ischemia using SPECT.Methods This study was an open,multi-center,randomized and positively controlled trial with crossover references.It consisted of 120patients clinically confirmed or suspected of myocardial ischemia.Each patient underwent a resting MPI and two separate stress MPI in a randomized crossover manner with intravenous administration of HG or adenosine (Ad) on different days.The severity and extent of myocardial ischemia were diagnosed on stress MPI.The degree of vascular stenosis in terms of percentage narrowing was measured by CAG (＞50％ was defined as coronary disease),thus defined as gold standard.The diagnostic efficacy of HG and Ad was compared.Vital signs,routine blood and urine tests,blood biochemical items and side effects were documented for evaluation of procedure safety.Two-sample t test,x2 or Fisher's exact test,and Kappa test were used.Results A total of 109 patients completed the trim and CAG.The diagnostic sensitivity,specificity,accuracy,positive predictive value,negative predictive value of HG MPI were 56.1％ (32/57),78.8％ (41/52),67.0％(73/109),74.4％ (32/43) and 62.1％ (41/66),respectively,which were not significantly different from those ofAd MPI (52.6％ (30/57),82.7％ (43/52),67.0％ (73/109),76.9％ (30/39) and 61.4％(43/70) ;x2 =0-0.2476,all P＞0.05).The sensitivity of HG vs Ad MPI in the diagnosis of single-,double-and triple-vessel ischemia was 29.6％ (8/27) vs 22.2％ (6/27),64.7％ (11/17) vs 64.7％ (11/17)and 100％ (13/13) vs 100％ (13/13),respectively.The concordance between HG and Ad for the detection of LAD,LCX and RCA ischemia was 95.41％ (104/109),97.25％ (106/109) and 97.25％ (106/109) (Kappa=0.8905,0.8420 and 0.8874).HG did not induce significant systolic blood pressure change during or after administration.Both HG and Ad could induce temporary decrease of diastolic blood pressure.Either HG or Ad induced significantly increased HR during administration and 5 min after administration.The clinical laboratory profile (hematology,serum chemistry,and urinalysis) was either normal or with no significant change.A total of 176 side effects (e.g,dyspnea,short breath,palpitation,dizziness,headache) were found related to HG (69.2％,83/120) and Ad (77.5％,93/120) administration (x2=2.1307,P＞0.05),which were mostly mild and transient.Conclusion HG is a safe and effective pharmacological stress test agent as compared to adenosine for the detection of CAD with SPECT perfusion imaging.

Objective To synthesize 68 Ga-1,4,7,10-tetraazacyclododecane-N,N',N,N()-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide (68Ga-DOTATATE) manually and automatically,validate its qualities in vitro,and evaluate its biodistribution in ICR mice and the microPET imaging in nude mice bearing pancreatic AR42J tumor.Methods 68Ga-DOTATATE was synthesized by automatic method using commercial metal isotope multifunctional module with strong cation exchange (SCX) column and by manual method.Both the products were measured for quality control.For the biodistribution study 5 groups of ICR mice were injected with 68Ga-DOTATATE(1.11 MBq) and executed at 10,30,60,120 and 240 min postinjection,respectively.The organs were weighted,and ％ ID/g was calculated.Nude mice bearing pancreatic AR42J tumor were intravenously injected with 3.7 MBq 68Ga-DOTATATE,and then microPET imaging was acquired at 10,30,60,120,18 and 240 min.Results 68Ga-DOTATATE could be successfully synthesized by the automatic and manual methods.Both the product injections were colorless and clear.The pH value was 6.5±0.1.For the products obtained from the two methods,the radiochemical purities were over 99％,and the products were stable for 4 h at room temperature.For the automatic method,68Ga-DOTATATE was synthesized within 30 min and with the radiochemical yield of (51.8±3.2)％ (time decay corrected).For the manual method,the time used for the synthesis was 20 min,and the labeling yield was over 99％.Three batches of the products were aseptic and pyrogen-free.In ICR mice,68Ga-DOTATATE was excreted by the kidney,and showed relatively high accumulation in the liver,spleen,pancreas and adrenal glands,while lower in the bone and soft tissue.The clearance from blood was fast with (4.41±0.81) ％ID/g at 10 min postinjection and (0.78 ± 0.32) ％ ID/g at 1 h.MicroPET imaging showed increased uptake of 68GaDOTATATE in the tumor tissues,and T/NT were 2.01±0.29(10 min),6.74±2.90(30 min) and 4.46±2.05 (60 min),respectively.Conclusions 68 Ga-DOTATATE could be successfully synthesized manually and automatically.The products reach to the specification of radioactive drugs and could be used as an attractive positron emitting radiotracer for detection of the somatostatin receptor-positive tumors.

Objective To investigate the feasibility of using low Kv,low iodine contrast Agent concentration (dual low)CT scan techniques in Coronary CTA (CCTA).Methods Seventy-six patients undergoing CCTA were divided into Group A and Group B , randomly.Group A (38 patients)was the dual-low group,which was scanned with tube voltage of 100 kVp,and injected with iso-osmolarity contrast agent visipaque 270 (270 mg I/mL),with iterative reconstruction technique (ASIR 40%).Group B (38 pa-tients)was scanned with 120 kVp,and low osmolarity contrast agent omnipaque 350 (350 mg I/mL)and FBP reconstruction,The images are assessed double-blindly by two experienced radiologists.Five ROIs were placed onto the ascending root of aorta (AO), left main artery(LM),left anterior descending (LAD),left circumflex artery(LCX),right coronary artery (RCA),and the image qualities are evaluated objectively using CT values,noise,signal noise ratio (SNR),contrast noise ratio (CNR),and compared sta-tistically using Paired t-test.The radiation dosages,such as CTDIvol,DLP and ED were also recorded and compared with Paired t-test.Results CTDIvol,DLP and ED of Group A (dual low)decreased 35.7%,38.6% and 38.6% respectively compared with Group B,the iodine intake decreased 22.9%.While the image qualities of the two groups were not significantly different,all images are good enough for diagnosis,with Group A slightly better than Group B in radiologists’scores.Conclusion Voltage 100 kVp, combined with low contrast agent concentration of 270 mg I/mL can fully satisfy the diagnostics need in CCTA,and significantly lower both the radiation dosage and iodine intake.

OBJECTIVE:To establish a method for the simultaneous determination of chlorogenic acid,vitexin glucoside,vi-texin rhamnoside,vitexin,rutin and hyperoside in Crataegus pinnatifida. METHODS:With reference peak of vitexin glucoside, HPLC was conducted to calculate the relative correction factor(RCF)of chlorogenic acid,vitexin glucoside,vitexin rhamnoside, vitexin,rutin and hyperoside,then the contents of above-mentioned 5 components in C. pinnatifida were calculated. The column was Agilent ZORBAX SB C18 with mobile phase of 0.1% formic acid-acetonitrile-tetrahydrofuran (gradient elution) at a flow rate of 1.0 ml/min,the detection wavelength was 350 nm,column temperature was 30 ℃,and the injection volume was 10 μl. RE-SULTS:The linear range was 12.50-400.0 μg for chlorogenic acid(r=0.999 8),25.00-800.0 μg for vitexin glucoside(r=0.999 9), 31.25-1 000.0 μg for vitexin rhamnoside(r=0.999 9),6.470-260.0 μg for vitexin(r=0.999 9),2.50-80.0 μg for rutin(r=0.999 8) and 9.375-300.0 μg for hyperoside(r=0.999 9);RSDs of precision,stability and reproducibility tests were lower than 2.0%;re-coveries were 99.2%-103.9%(RSD=1.6%,n=6),97.9%-100.8%(RSD=1.2%,n=6),99.2%-100.8%(RSD=0.5%,n=6), 97.3%-101.3%(RSD=1.5%,n=6),98.0%-103.0%(RSD=1.9%,n=6)and 95.5%-101.5%(RSD=2.2%,n=6). RCFs of vitex-in glucoside with chlorogenic acid,vitexin rhamnoside,vitexin,rutin and hyperoside were 1.119,1.009,0.706,1.063 and 0.830, respectively. CONCLUSIONS:The method is simple with good precision,stability and reproducibility,and it can be sued for the simultaneous determination of 6 components in C. pinnatifida.

Objective To analyze the clinical and pathological features of advanced colorectal serrated adenoma(ACSA). Methods The endoscopic and pathological features of 156 cases of ACSA and 121 cases of non-ACSA diagnosed in General Hospital, Tianjin Medical University from January 2010 to March 2016 were retrospectively analyzed and compared.Results ACSA and non-ACSA cases accounted for 56.3%(156/277)and 43.7%(121/277)of all patients with colorectal serrated lesions,respectively. The mean age of ACSA patients was 57.79±13.65 years and 89(57.1%)of these patients were male. There was no significant difference in age and gender between ACSA and non-ACSA patients. A total of 161 ACSA lesions were diagnosed,including 71 sessile serrated adenoma/polyps and 90 traditional serrated adenomas. Among the 161 ACSA lesions,there were 29(18.0%)lesions whose diameter≥10 mm, and 84(52.2%) lesions located in the proximal colon, which were more than non-ACSA(84/161 VS 49/134,P=0.007). ACSA was classified under endoscopy into pedunculated type(20/161),sub-pedunculated type(35/161), sessile type(24/161),flat type(79/161)and laterally spreading tumor(3/161), and the distribution of lesion type was significantly different from non-ACSA(P<0.001). One hundred and sixty(99.4%)ACSA lesions were diagnosed as dysplasia, including 158 low degree dysplasia and 2 high degree dysplasia.Moreover,16 ACSA patients were accompanied with synchronous advanced colorectal neoplasia(sACN), and large serrated polyps(diameter≥10 mm)might have a strong association with sACN(OR=4.35, 95%CI:1.467-12.894, P<0.05). Conclusion ACSA is more common in proximal colon and sub-pedunculated type,sessile type and flat type. ACSA diameter≥10 mm is significantly associated with sACN.

The study was to observe the therapeutic effect of HJ-1 NO--HFJV respirator on treating pulmonary edema caused by seawater drowning. Seawater was infused into the rabbit's lung to establish the animal model of pulmonary edema caused by seawater drowning(PE-SWD). Then the animals were divided into three groups: simple PE-SWD model as control group, treat group(animal model treated with HFJV respirator and four medicines) and HFJV respiratior plus NO group. Pao2, Sao2 and pH were measured by the blood-gas analyzer. The survival time and seawater drowing-respiratiory distress syndrom(SW-RDS) were observed. The results showed that Pao2, Sao2 in NO group were remarkably higher than that of PE-SWD control group, and the survival time was longer than that of medicine treated group and the incidence of SW-RDS decreased to zero. We assume that HJ-1 NO-HFJV respirator is efficient on treating pulmonary edema.
Animals ; Disease Models, Animal ; High-Frequency Jet Ventilation ; instrumentation ; Near Drowning ; complications ; Nitric Oxide ; therapeutic use ; Pulmonary Edema ; etiology ; therapy ; Rabbits

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Objective:To evaluate the diagnostic value of 99Tc m-pyrophosphate (PYP) in transthyretin cardiac amyloidosis. Methods:From December 2018 to July 2019, 17 patients (9 males, 8 females, age: (53.4±13.0) years) with suspected cardiac amyloidosis underwent 99Tc m-PYP imaging in Peking Union Medical College Hospital were prospectively included. Visual score and semi-quantitative values (heart to contralateral ratio, H/CL) of 99Tc m-PYP uptake were used to diagnose transthyretin amyloidosis (ATTR). Biopsies and genetic measurements were also developed to evaluate the diagnostic value of the imaging. Results:Five of the 17 patients were diagnosed as ATTR with a visual score of 2-3, H/CL≥1.5, and confirmed with the biopsy or gene test. Four patients were diagnosed as ATTR with positive genetic results but no cardiac symptoms, and their visual scores were between 0 and 1 with H/CL<1.5. Considering the young age of the patients, amyloid deposition might have not yet caused visceral damage. Visual score of other 8 patients with negative 99Tc m-PYP imaging were also between 0 and 1 with H/CL<1.5, 2 of 8 were confirmed with light chain amyloidosis (AL) by biopsy, 3 were clinically diagnosed as AL and 3 were ATTR excluded. The accuracy of 99Tc m-PYP imaging for diagnosing ATTR was 11/11. Conclusion:99Tc m-PYP imaging is helpful for non-invasive diagnosis of transthyretin cardiac amyloidosis.

OBJECTIVE To determi ne the contents of total fla vonoids i n Scutellaria barbata standard decoction ，evaluate in vitro antioxidant activity ，establish the fingerprint and conduct chemical pattern recognition analysis. METHODS The contents of total flavonoids in S. barbata standard decoction （calculated by scutellarein ）were determined by ultraviet-visible spectrophotometry. In vitro antioxidant activity of S. barbata standard decoction was investigated by free radical scavenging tests of 1，1-diphenyl- 2-trinitrophenylhydrazine（DPPH）and 2，2′-azino-bis（3-ethylbenzothiazoline-6-sulfonic acid ）ammonium salt （ABTS）；HPLC method was adopted. Using scutellarin as reference ，the fingerprints of 16 batches of S. barbata standard decoction were drawn and evaluated by Similarity Evaluation System of TCM Chromatogram Fingerprint （2004 A edition ），and the common peaks were determined；Pearson correlation analysis was carried out by using SPSS 24.0 software to screen substances with in vitro antioxidant activity. Taking them as variables ，cluster analysis and principal component analysis were carried out by using SPSS 24.0 and SIMCA 14.1 software. RESULTS The linear range of total flavonoids were 2.106-21.06 μg/mL（R2＝0.999 3）；RSDs of precision ， reproducibility and stability tests （120 min）were all lower than 2％；the recovery was 100.62％（RSD＝0.55％，n＝6）；the contents of total flavonoids were 0.634-1.053 mg/mL. Median inhibitory concentration （IC50） of DPPH radical scavenging experiment ranged 1.120-3.602 mg/mL，and IC 50 of ABTS radical scavenging e xperiment range d 0.684-1.327 mg/mL. The results of correlation analysis showed that the content of total flavonoids Δ 基金项目 ：河北省高校省级重点学科建设项目 （No.冀教 in S. barbata standard decoction was negatively correlated 高〔2013〕4号）；承德医学院自然科学研究计划项目（No.201824） ＊讲师，硕士。研究方向：中药质量控制 。电话：0314-2291186。 with the IC 50 of DPPH free radical and ABTS free radical E-mail：duyilongww@sina.com scavenging experiment ，and the correlation coefficients were # 通信作者 ：教授，硕士。研究方向 ：中药质量控制 。电话： －0.976 and －0.940 respectively（P＜0.01）. There were 18 0314-2291186。E-mail：phf2301@163.com common peaks in the fin gerprints of 16 batches of S. barbata 中国药房 2022年第33卷第4期 China Pharmacy 2022Vol. 33 No. 4 ·425· standard decoction ；the s imilarities were 0.964-0.997. A total of 4 common peaks were identified ，such as scutellarin （peak 8）， scutellarein（peak 14），luteolin（peak 15），apigenin（peak 17）.In the HPLC fingerprints of S. barbata standard decoction ，the peak areas of peak 3-4，8-9，12-15 and 17 were significantly negatively correlated with the IC 50 of DPPH free radical and ABTS free radical scavenging experiment （P＜0.05）. The results of cluster analysis showed that 16 batches of S. barbata standard decoction could be clustered into two categories ，of which S 2，S7-S8 and S 14-S16 were clustered into one category ，S1，S3-S6 and S 9-S13 were clustered into one category. By principal component analysis ，16 batches of S. barbata standard decoction were divided into two categories ，of which S 2，S4，S7 and S 14-S16 were clustered into one category ，and S 1，S3，S5-S6 and S 8-S13 were clustered into one. The comprehensive scores were high in the samples of S 4，S13，S15. CONCLUSIONS Established HPLC fingerprint and chemical pattern recognition analysis method can be used to evaluate the quality of S. barbata standard decoction ； peak 3-4，8-9，12-15 and 17 and total flavonoids are the potential material basis for S. barbata standard decoction to scavenge DPPH free radical and ABTS free radical.