浙江人群幽门螺杆菌cagA/vacA优势基因型和不同基因型混合感染的调查

目的　了解消化性溃疡和慢性胃炎患者感染的幽门螺杆菌 (Hp)cagA vacA优势基因型及不同基因型Hp感染、混合感染与疾病的关系。 方法　选择胃窦、胃体双份活检标本均培养出Hp的 42例慢性胃炎 (CG)和 3 6例消化性溃疡 (PU )患者作为研究对象 ,采用聚合酶链反应 (PCR)检测156份Hp分离株的cagA基因、vacA基因的信号区 (s)和中间区 (m )亚型 ,分析Hp基因型及多株Hp混合感染在CG和PU中的分布。结果　胃窦标本cagA基因的检测中 78例患者中有 75例 (96.2 % )为cagA阳性 ,相应的胃体标本中 ,76例患者 (97.4% )为cagA阳性 ,有 1例 (1.3 % )患者胃窦、胃体检出cagA状态不一的Hp混合菌株。在胃窦标本的vacA基因分型中 ,s1a m1、s1a m2、s1a m1b、s1a m1b m2 4种vacA基因型在 78例患者中所占比例分别为 6.4% (5 78)、55.1% (43 78)、2 6.9% (2 1 78)和 1.3 % (1 78) ,多株混合感染为 3 .8% (3 78) ;而相应的胃体标本中 ,前述四种vacA基因型所占比例依次为 6.4% (5 78)、53 .8% (42 78)、2 5.6% (2 0 78)和 3 .8% (3 78) ,多株混合感染为 5.1% (4 78)。cagA+ s1a m2和cagA+ s1a m1b在胃窦标本中占 51.3 % (40 78)和 2 6.9% (2 1 78) ,而在相应的胃体标本中占 52 .6% (41 78)和 2 5.6% (2 0 78)。少量胃窦、胃体     

67Ga心肌炎症显像对小儿病毒性心肌炎的诊断价值

目的 :探讨6 7Ga心肌显像对小儿病毒性心肌炎 (VMC)诊断的临床价值。方法 :静脉注射6 7Ga 枸橼酸盐 ,48h、72h后开始显像 ,观察心脏部位放射性浓聚情况 ,并计算心 /肺 (H/L)指数 ,根据H/L指数判断心肌炎性病变的严重程度 (H/L指数 >1.2为阳性 )。结果 :78例病毒性心肌炎患儿中 ,50例阳性 (占 64% ) ,其中急性期阳性率为 84% ,恢复期阳性率为 50 % ,慢性期为 2 9% ,急性期阳性率明显高于恢复期和慢性期 (P<0 .0 5)。结论 :心肌6 7Ga放射性浓聚与心肌炎病变程度呈正相关 ,直接反映了病变心肌的炎症反应情况 ,对诊断VMC有较高的临床价值 ,并对VMC治疗、预后有指导作用     

Cyclotron production of carrier-free 66Ga as a positron emitting label of albumin colloids for clinical use

A method for producing carrier free ⁶⁶Ga (T_1/2:9.4h; ⁺) by ⁴He bombardment of natural copper targets is presented. ⁶⁶Ga is formed by means of the ⁶³Cu (⁴He, n) ⁶⁶Ga reaction. Production yields are given in the 17.5 to 8 MeV ⁴He energy range. Chemical purification of ⁶⁶Ga from the copper target is described. The only radionuclidic impurity found in the final product was ⁶⁷Ga. Albumin colloids from commercially available kits designed for use with ^99mTc could easily be labeled with ⁶⁶Ga and employed for studies of the lymphatic system by positron emission tomography.     

Equine herpesvirus type 1 infected cell polypeptides: evidence for immediate early/early/late regulation of viral gene expression

EHV-1 polypeptide synthesis was examined in productively infected rabbit kidney and hamster embryo cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses of extracts from [35S]methionine- and 3H-amino acid-labeled-infected and mock-infected cultures revealed the presence of 30 infected cell-specific polypeptides (ICPs) which ranged in apparent molecular weights from 16.5K to 213K. Twenty-two of these ICPs comigrated with virion structural proteins. Four ICPs (203K, 176K, 151K, 129K) were detected in extracts of infected cultures labeled in the presence or absence of actinomycin D (Act D) immediately after release from a 4-hr treatment with cycloheximide (CH). These polypeptides, which were designated as EHV-1 immediate early (alpha) ICPs, were not detected in unblocked (non-CH-treated) infected cells. The most abundant ICP was a 31.5K nonstructural protein which, in addition to a 74K protein, was detected in unblocked infected cells at 2-3 hr postinfection. These proteins appeared to be regulated as early (beta) ICPs, since neither protein was observed in Act D-treated cultures released from CH block. Twelve ICPs were classified as late (gamma) polypeptides on the basis of their reduced synthesis in cultures in which viral DNA replication was inhibited by phosphonoacetic acid. All but one (40K) of these late ICPs corresponded to virion structural proteins.     

Exploring the radiosynthesis and in vitro characteristics of [68Ga]Ga‐DOTA‐Siglec‐9

Vascular adhesion protein 1 is a leukocyte homing‐associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283–297 of sialic acid‐binding IgG‐like lectin 9 (Siglec‐9) “CARLSLSWRGLTLCPSK” bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([⁶⁸Ga]Ga‐DOTA‐Siglec‐9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [⁶⁸Ga]Ga‐DOTA‐Siglec‐9 are presented and compared with previously published methods. A simple, robust radiosynthesis of [⁶⁸Ga]Ga‐DOTA‐Siglec‐9 with a yield of 62% (non decay‐corrected) was identified, and it had a radiochemical purity >98% and a specific radioactivity of 35 MBq/nmol. Furthermore, the protein binding and stability of [⁶⁸Ga]Ga‐DOTA‐Siglec‐9 were analyzed in vitro in mouse, rat, rabbit, pig, and human plasma and compared with in vivo pig results. The plasma in vitro protein binding of [⁶⁸Ga]Ga‐DOTA‐Siglec‐9 was the lowest in the pig followed by rabbit, human, rat, and mouse. It was considerably higher in the in vivo pig experiments. The in vivo stability in pigs was lower than the in vitro stability. Despite considerable species differences, the observed characteristics of [⁶⁸Ga]Ga‐DOTA‐Siglec‐9 are suitable as a positron emission tomography tracer.     

Diagnosing infection of extracardiac conduit in children

Summary Between August 1985 and July 1992, at our center, 142 Japanese children had an extracardiac conduit operation to reconstruct the right ventricular outflow tract. The study group consisted of 22 of these 142 children who had a persistent fever and whose serum was positive for acute-phase reactants after the operation. We present the diagnostic findings for 10 children with infection of an extracardiac conduit that had been placed to restore the continuity of the right ventricle-pulmonary artery. They were part of the group of 22 children who were followed over the past 7 years with blood cultures, echocardiography, and⁶⁷Ga imaging. All 10 developed a persistent fever and were seropositive for acute-phase reactants. Conduit infection was diagnosed in only 2 patients by the detection of vegetation on echocardiography and was diagnosed in 9 of the 10 patients by an abnormal⁶⁷Ga uptake in the area of the artificial vessels used to reconstruct the pulmonary artery. The present study compared the use of blood cultures, echocardiography, and⁶⁷Ga imaging in diagnosing an infection of the extracardiac conduit. The sensitivity of blood cultures in diagnosing an extracardiac conduit infection was 70% (7/10), and the specificity was 92% (1/12).⁶⁷Ga imaging showed a higher sensitivity than echocardiography in diagnosing infection of an extracardiac conduit.     

Automated synthesis of 68Ga/177Lu-PSMA on the Trasis miniAllinOne

Prostate-specific membrane antigen (PSMA)-based radioligands for positron emission tomography (PET)/computed tomography (CT) studies represent the gold standard for detection of recurrent prostate cancer (PCa). [⁶⁸Ga]PSMA-HBED-CC is a PET radiotracer suitable for detection of PCa, and its clinical use has become widespread over the last few years. In this contribution, we detail our GMP-compliant production of [⁶⁸Ga]PSMA-HBED-CC using the Trasis miniAllinOne radiosynthesizer and report synthetic and clinical data for the first 100 productions of 2019. Additionally, we detail our efforts towards a GMP-compliant production of the radiotherapeutic [¹⁷⁷Lu]PSMA-I&T using the same synthesis module. PSMA-based radioligand therapy (RLT) offers a possible future treatment in cases of metastatic castration-resistant PCa, and GMP-compliant routine production methods are therefore called for. This report highlights how PSMA-based agents for theranostic purposes can be conveniently produced at a single radiochemistry Good Manufacturing Practice (GMP) site, thereby facilitating optimized detection and treatment of PCa.     

Preclinical evaluation of potential infection‐imaging probe [68Ga]Ga‐DOTA‐K‐A9 in sterile and infectious inflammation

The development of bacteria‐specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N?‐tetraacetic acid (DOTA) conjugated peptide [⁶⁸Ga]Ga‐DOTA‐K‐A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [⁶⁸Ga]Ga‐DOTA‐K‐A9 synthesis omitting the use of acetone was developed, yielding 93 ± 0.9% radiochemical purity. The in vivo infection binding specificity of [⁶⁸Ga]Ga‐DOTA‐K‐A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine‐induced inflammation and compared with 2‐deoxy‐2‐[¹⁸F]fluoro‐D‐glucose ([¹⁸F]FDG). The scans showed that [⁶⁸Ga]Ga‐DOTA‐K‐A9 accumulated in all the infected mice at injected doses ≥3.6 MBq. However, the tracer was not found to be selective towards infection, since the [⁶⁸Ga]Ga‐DOTA‐K‐A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5‐carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA‐K‐A9, the microscopy results suggested that TAMRA‐K‐A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [⁶⁸Ga]Ga‐DOTA‐K‐A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria.     

Automated production of [68Ga]Ga‐DOTANOC and [68Ga]Ga‐PSMA‐11 using a TRACERlab FXFN synthesis module

The interest in gallium‐68 labelled positron‐emission tomography probes continues to increase around the world. However, one of the barriers for routine clinical use is the cost of the automated synthesis units for relatively simple labelling procedures. Herein, we describe the adaptation of a TRACERlab FX_FN synthesis module for the automated production of gallium‐68 radiopharmaceuticals using a cation‐exchange cartridge for postprocessing of the ⁶⁸Ge/⁶⁸Ga generator eluate. The recovery of activity from the cartridge was 95.6% to 98.9% using solutions of acidified sodium chloride (5 M with pH = 1‐3). The radiosyntheses of [⁶⁸Ga]Ga‐DOTANOC and [⁶⁸Ga]Ga‐PSMA‐11 were performed using acetate sodium buffer or 4‐(2‐hydroxyethyl)piperazine‐1‐ethanesulfonic acid, with a total duration of 21 and 23 minutes, respectively, including generator elution and radiopharmaceutical dispensing. Activity yields were 77% ± 2% for [⁶⁸Ga]Ga‐PSMA‐11 and 68% ± 3% for [⁶⁸Ga]Ga‐DOTANOC (n > 100). The labelled peptides had a radiochemical purity exceeding 97%, and all quality control parameters were in conformity with the limits prescribed by the European Pharmacopoeia.     

Bis(Methylpyridine)‐EDTA Derivative as a Potential Ligand for PET Imaging: Synthesis,Complexation, and Biological Evaluation

A novel transitional metal ligand derivatized from EDTA‐conjugated 2‐amino‐4‐methyl pyridine, an acyclic vehicle (EDTA‐Mepy₂) was designed, synthesized, and characterized for PET imaging with ⁶⁸Ga. The drug likeliness and appropriate lipophilicity were first analyzed by molecular docking studies which shows interactive property of ligand with serum albumin protein (HSA: PDB 1E78), at Lys199, Arg257, and His242 residues, which make it more appropriate in transportation as a specific ligand for PET imaging. As a confirmation, binding constant of the ligand with human serum albumin was calculated at λ_ex = 350 nm which was found to be 4.9 × 10³ m ^?1. The pharmacokinetics of ⁶⁸Ga‐EDTA‐Mepy₂ was analyzed by blood kinetics (t_1/2 slow: 3 h 56 min and t_1/2 fast: 32 min) and biodistribution (maximum%ID/g was found in kidney at 1 h). Further the capability of this ligand was analyzed as optical marker also, by recording λ_ex = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed λ_em = 280 nm. Additionally, in physiological conditions where its stability was calculated, suggests 15–20 times selectivity over the endogenously present metal ions (K_GaL/K_ZnL = 14.3, K_GaL/K_CuL = 18.1).