A competitive indirect time-resolved fluoroimmunoassay(TRFIA) was developed for detection of zearalenone(ZEN) in cereals,in which ZEN conjugated to bovine serum albumin(BSA) is used as solid-phase antigen.A competitiv...A competitive indirect time-resolved fluoroimmunoassay(TRFIA) was developed for detection of zearalenone(ZEN) in cereals,in which ZEN conjugated to bovine serum albumin(BSA) is used as solid-phase antigen.A competitive indirect TRFIA was conducted by simultaneously incubating ZEN in standard or extracted samples with anti-ZEN monoclonal antibody over ZEN-BSA coated plates,and then determining the bound ZEN monoclonal antibody with goat anti-mouse europium conjugate.Samples were extracted with methanol/water...展开更多
A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in condi...A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in conditions of 0.1 mg SnCl2.2H2O at pH 6.0 and 99TcmO4? in aqueous solution for 20 min at room temperature. The labeling yield and radiochemical purity of 99Tcm-PIDP are both higher than 95%. The biodistribution results show that the bone uptake is up to 8.47% ID/g which is the maximum of bone uptake at 30 min after injection of 99Tcm-PIDP in mice. The pharmacokinetic parameters can be estimated from the exponential equation of C=59.565e-11.307t+2.069e-1.211t. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-PIDP. The results indicate that 99Tcm-PIDP has highly selective uptake in the skeletal and low uptake, rapid clearance in soft tissues, so it would be a potential novel bone imaging agent.展开更多
Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of t...Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value(SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer(CRC) in mice. Methods: Colorectal liver metastases(CRLM) xenograft models were established by injecting tumor cells(LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. ^(18)F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^(18)F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the ^(18)F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1 α(HIF-1 α) and serum starvation-induced glucose transporter 1(GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, ^(18)F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between ^(18)F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ^(18)F-FMISO SUVmax ratio and HIF-1 α or GLUT-1 expression in tumor-bearing tissues. Conclusions: ^(18)F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.展开更多
Asialoglycoprotein receptor(ASGP-R)is a hepatic membrane receptor that uniquely exists on the surface of mammalian hepatocytes,and has been used as target of liver functional imaging agents for many years.We labeled t...Asialoglycoprotein receptor(ASGP-R)is a hepatic membrane receptor that uniquely exists on the surface of mammalian hepatocytes,and has been used as target of liver functional imaging agents for many years.We labeled the Galactosyl-neoglycoalbumin(NGA)with 18F to get a PET molecular probe 18F-FB-NGA and evaluated its ability as a liver functional PET imaging agent.The 18F-FB-NGA was prepared with NGA by conjugation with Nsuccinimidyl-4-18F-fluorobenzoate(18F-SFB)and purified with PD-10 desalting column.The radiolabeling yield and radiochemical purity of 18F-FB-NGA were determined by radio-HPLC.Starting with 18F-F–,the total time for 18F-FB-NGA was about 120±10 min.The decay-corrected radiochemical yield is about 25–30%.The radiochemical purity of purified 18F-FB-NGA was more than 98%.Labeled with 185–1850 MBq 18F-SFB,the specific activity of 18F-FBNGA was estimated to be 7.83–78.3 TBq/mmol.Biodistribution of 18F-FB-NGA in normal mice was investigated after injection through the tail vein.The results showed that the liver accumulated 39.47±3.42 and 12.12±6.11%ID/g at 10 and 30 min after injection,respectively.Dynamic MicroPET images in mice were acquired with and without block after injection of the radiotracer,respectively.High liver activity accumulation was observed at 5 min after injection in normal group.On the contrary,the liver accumulation was significantly lower after block,indicating the specific binding to ASGP-R.18F-FB-NGA is probably a potential PET liver imaging agent.展开更多
Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correl...Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,^(68)Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer ^(68)Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.展开更多
Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with c...Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.展开更多
Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers pro...Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.展开更多
Technetium-99m-labeled-5-{2-sulfanylethyl-[2-(2-sulfanylethylamino)acetyl]amino}-methyl-2′-deoxy- uridine (99mTc-ANMdU) was reported. The precursor ANMdU was synthesized by six-step reactions and all intermediates we...Technetium-99m-labeled-5-{2-sulfanylethyl-[2-(2-sulfanylethylamino)acetyl]amino}-methyl-2′-deoxy- uridine (99mTc-ANMdU) was reported. The precursor ANMdU was synthesized by six-step reactions and all intermediates were verified with MS and 1HNMR. Using SnCl2 as reducing agent, a labeling reaction was carried out at 100°C for 30 min. The radiochemical purity of the 99mTc-ANMdU was 96.68%. Partition coefficients were 0.92 and 0.70 at pH 7.0 and 7.4 of the phosphate buffer saline, respectively. Biodistribution of 99mTc-ANMdU in normal mice showed that the initial uptake of 99mTc-ANMdU in vivo and the clearance was rapid.展开更多
TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99Tc...TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99TcmO4 with SnCl2·2H2O in aqueous solution for 10 min at room temperature. Both labeling yield and radiochemical - purity of Tcm-TADP were more than 95%. The biodistribution in rats and bone scan in rabbits were also studied. The 99 uptake of organ was expressed as %ID/g. The results showed that the bone uptake is up to 17.17%ID/g which is the maximum of bone uptake at 30 min after injection of Tcm-TADP in rats, bone-to-muscle and bone-to-blood uptake 99 ratios were 61.32 and 13.21, respectively. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-TADP and clearance in soft tissue was visible. The preparation of 99Tcm-TADP was convenient and 99Tcm-TADP exhibited high uptake in bone, and it would be a potential new bone imaging agent.展开更多
The interleukin-11(IL-11)and the IL-11 receptorα-subunit(IL-11Rα)have been demonstrated to regulate the invasion and proliferation of tumor cells.Our study intends to evaluate a noninvasive imaging of IL-11Rαexpres...The interleukin-11(IL-11)and the IL-11 receptorα-subunit(IL-11Rα)have been demonstrated to regulate the invasion and proliferation of tumor cells.Our study intends to evaluate a noninvasive imaging of IL-11Rαexpression in breast tumors using near-infrared(NIR)fluorescent dye Cy7-labeled IL-11 mimic peptide CGRRAGGSC.This work evaluated the IL-11Rαexpression of breast tumor cells and the binding status of this peptide to IL-11Rαin vitro and in vivo by using Western blotting,immunofluorescence staining and near-infrared fluorescence imaging.Our biochemical study showed that IL-11Rαwas overexpressed in breast tumor cells(MCF-7).The cell-binding assay demonstrated specific binding of peptide CGRRAGGSC to MCF-7 cells in vitro.In vivo imaging results showed that NIR fluorescent signals of Cy7-CGRRAGGSC were selectively accumulated in tumor and metabolic organs.While in the blocking experiment,free CGRRAGGSC obviously blocked the concentration of the Cy7-CGRRAGGSC in the tumors.These results suggested that IL-11Rαmay be used as a potential target for noninvasive imaging in IL-11Rαoverexpressed tumors.Furthermore,the imaging agent of near-infrared fluorescent dye Cy7-labeled CGRRAGGSC is suitable for IL-11Rαexpression imaging study in vivo.展开更多
The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stan...The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stannous fluoride (SnF 2 ) as reducing agent. Biological characteristics of 99m Tc-PQQE include lipophilic and the charge properties were compared to 99m Tc-PQQ. The biodistributions of 99m Tc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99m Tc-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2β) results indicate that the residence time of 99m Tc-PQQE (203.92) in the body is twice as long as 99m Tc-PQQ (100.45). The uptake of 99m Tc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99m Tc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99m Tc-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that 99m Tc-PQQE has some specific targeting to the NMDA receptor.展开更多
A novel zoledronic acid derivative,1-hydroxy-2-(2-butyl-1H-imidazole-1-yl)-ethylidene-l,l- diphosphonic acid(BIDP),was synthesized and labeled with ^(99)Tc^m.The detailed kinetic study on the labeling reaction between...A novel zoledronic acid derivative,1-hydroxy-2-(2-butyl-1H-imidazole-1-yl)-ethylidene-l,l- diphosphonic acid(BIDP),was synthesized and labeled with ^(99)Tc^m.The detailed kinetic study on the labeling reaction between BIDP and ^(99)Tc^m was carried out.The results indicated that the reaction rate constants k were 0.0258,0.0268, 0.0305,0.0323,0.0351 and 0.0384 min^(-1)at 0℃,5℃,10℃,15℃,20℃and 25℃,respectively.From the Arrhenius equation k=A·e^(-E_Δ/(RT)),the activation energy E_a of the labeling reaction was calculated to be 10.45 kJ/mol.And the correlation between k and temperature(T)was also deduced as In k=-1258.8×(l/T)+0.9531.In addition,it was found that in order to get a high radiolabeling yield(RLY)(>90%),the reaction temperature must be up to 12℃.展开更多
To evaluate the clinical value of combined determination of serum PGⅠ, PGⅡ and GAS for early diag-nosis of gastric cancer, the serum levels of PGⅠ, PGⅡ and GAS in 190 healthy controls and 129 patients with gas-tri...To evaluate the clinical value of combined determination of serum PGⅠ, PGⅡ and GAS for early diag-nosis of gastric cancer, the serum levels of PGⅠ, PGⅡ and GAS in 190 healthy controls and 129 patients with gas-tric disorders were measured by RIA. The 129 patients include 68 cases of gastric cancer. The results showed that the serum levels of PGⅠ and PGⅠ/PGⅡ ratio in gastric cancer patients were obviously lower than those in healthy controls, while comparing with controls, the serum GAS levels were significantly higher. The diagnostic accuracy of the determinations for gastric cancer was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) levels of serum PGⅠ, PGⅠ/PGⅡ ratio and GAS were 0.833, 0.842 and 0.851, respec-tively. As serum PGⅠ or PGⅠ/PGⅡ ratio or GAS were combined, the sensitivity and specificity of determination for gastric cancer diagnosis were 94.2% and 73.4%, respectively. All these results indicated that the combined deter-mination of serum PGⅠ, PGⅡ and GAS levels may be used as a tool for primary screening of gastric cancer.展开更多
The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-memantine.The affinity and specificity...The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-memantine.The affinity and specificity were determined by radio-ligand receptor binding assay(RRA).Biodistribution in vivo in mice was performed.The results showed that ^(99)Tc^m-N-ethyl-N_2S_2-memantine bound to a single site on NMDA receptor with a K_d of 584.32 nmol/L and a B_(max)of 267.05 nmol/mg.A competitive analysis showed that such specific binding could be inhibited by specific inhibitors of NMDA receptor,such as ketamine and(+)-MK-801.The biodistribution exhibited rapid uptake and favorable retention in mice brains.The major radioactivity was metabolized by the hepatic system.A two-compartment model of C=4.49e^(-0.083t)+ 1.42e^(-0.0016t)was established,and the half life was 8.35 min in blood.In conclusion,the new radio-ligand ^(99)Tc^m-N-ethyl-N_2S_2-Memantine has a moderate affinity and specific binding to NMDA receptor,and can easily cross the blood-brain barrier(BBB).Therefore,it may be a potential NMDA receptor imaging agent.展开更多
Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimer's disease(AD). The existence of neurofibrillary tangles(NFTs) consisting of tau p...Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimer's disease(AD). The existence of neurofibrillary tangles(NFTs) consisting of tau protein are one kind of the pathological features of AD, and its level of severity is correlated with the stage of AD.However, no clinically approved positron emission tomography(PET) probe is currently available for selective imaging of neurofibrillary tangles on patients. In this paper, we report our studies on biological characteristics of [18F]-THK523 as a novel tau imaging probe. With low molecular weight, [18F]-THK523 is stable, electrically neutral, lipophilic and non-mass concentration-dependent. Preliminary biological studies have shown the excellent properties of [18F]-THK523 as brain imaging tracer for further research.展开更多
Extensive accumulation of neurofibrillary tangles(NFTs)consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer's disease.However,no PET probe i...Extensive accumulation of neurofibrillary tangles(NFTs)consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer's disease.However,no PET probe is currently available for selective detection of NFTs in the living human brain.[^(18)F]-THK523 was developed as a potential in vivo imaging probe for tau pathology.In this paper,we report a new protected precursor,2-((2-(4-((tert-butoxycarbonyl)amino)phenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(THK-7),instead of2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(BF241),and an improved automated radiosynfhesis of[^(18)F]-THK523 and the study on chemical kinetics of the labeling reaction of[^(18)F]-THK523,with high-yield(70±5%,n=6,decay-corrected to end of bombardment),and high radiochemical purity(>90%)and specific activity(2.5±0.5Ci/umol)from protected precursor on fully automated module at the end of radiosynthesis(45-55 min).The chemical kinetics for[^(18)F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.展开更多
This work was to develop a semi-automated synthesis of 18F-9-fluoropropyl-9-desmethyl-DTBZ (18F-FP-DTBZ) and validate its potential as a vesicular monoamine transporter 2 (VMAT2) ligand.18F-FP-DTBZ was synthesized by ...This work was to develop a semi-automated synthesis of 18F-9-fluoropropyl-9-desmethyl-DTBZ (18F-FP-DTBZ) and validate its potential as a vesicular monoamine transporter 2 (VMAT2) ligand.18F-FP-DTBZ was synthesized by a semi-automated procedure in a 21-35% yield without decay correction and with a radiochemical purity of >98%.Bioistribution in rats exhibited a favorable brain uptakes of the ligand (0.31±0.04 ID% at 60min post injection,n=8).The highest radioactivity located in VMAT2 enriched striatal tissue.The target-to-nontarget ratio (striatum/cerebellum,ST/CB) was 4.81±0.84.Blocking studies implied that striatum uptake could be blocked by DTBZ (a VMAT2 inhibitor) but could not by CFT (a dopamine transporter inhibitor).MicroPET imaging with 18F-FP-DTBZ in normal rats gave high quality images in which high radioactivity were observed in the striatal tissue.Time-and-activity curves revealed good retention in the target (striatum) and rapid clearance in the background (cerebellum),which resulted in a maximum ST/CB ratio of 5.08±0.81 (n=3) in 80-120min.By contrast,the 6-hydroxydopamine unilateral lesioned rats gave asymmetrical striata images with higher 18F-FP-DTBZ concentration on the unlesioned side (unlesioned-ST/CB=5.21±0.38,n=3) than the lesioned (lesioned-ST/CB=2.34±0.51).The results validated that 18F-FP-DTBZ is a favorable PET ligand binding to VMAT2.展开更多
This work was to investigate the pharmacologic characteristics of 18F-FECNT (2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane) as a dopamine transporter (DAT) PET imaging agent. Its partition co...This work was to investigate the pharmacologic characteristics of 18F-FECNT (2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane) as a dopamine transporter (DAT) PET imaging agent. Its partition coefficients were determined in n-octanol and phosphate buffer (PB) (pH 7.0 and pH 7.4). 6-Hydroxydopamine (6-OHDA) left-sided lesioned Parkinsonian rats were established and validated by rotational behavior tests. Biodistribution in vivo in mice, autoradiography in normal and hemi-Parkinsonian rat brains, and toxicity test were performed. The results showed that partition coefficients were 34.14 (pH 7.0) and 56.41 (pH 7.4), respectively. Biodistribution exhibited rapid uptake and favorable retention in the mice brains. The major radioactivity was metabolized by the hepatic system. The autoradiography showed that 18F-FECNT was highly concentrated in striatum, and that the left and the right striatal uptake were symmetrical in normal SD rat brains. In left-sided lesioned PD rat brains, the striatal uptake of 18F-FECNT bilaterally decreased in comparison with normal rats. No significant uptake was visible in the 6-OHDA lesioned-sided striatal areas. The results demonstrated that 18F-FECNT binds to DAT was specific. Toxicity trial displayed that the acceptable dose per kilogram to mice was 625 times greater than that to human. These indicate that 18F-FECNT is a potentially safe and useful DAT PET imaging agent in the brain.展开更多
In this work,a calculation method of chemical kinetics was established for labeling reaction of 99mTc-N-ethyl-N2S2-memantine,a potential NMDA receptor imaging agent prepared in our laboratory.Four groups of vials (3 v...In this work,a calculation method of chemical kinetics was established for labeling reaction of 99mTc-N-ethyl-N2S2-memantine,a potential NMDA receptor imaging agent prepared in our laboratory.Four groups of vials (3 vials per group) were added with 0.02 mL (1 mg/mL) N-ethyl-N2S2Memantine,0.08 mL (40 mg/mL) GH,0.05 mL (10 mg/mL) EDTA-2Na,0.035 mL (2 mg/mL) SnF2,0.8 mL phosphate buffer(1mol/L,pH 6.5) and 37 MBq Na99mTcO4.The vials were incubated at 70℃,80℃,90℃ or 100℃.Samples were taken with capillary from the vials at 2,5,10,20,30,40 and 60min.Labeling yields were determined by TLC.Order of reaction n,rate constant k,activation energy Ea and half life t1/2 of labeling reaction were calculated with the kinetics software we compiled.Mean labeling yields of 99m Tc-N-ethyl-N2S2-memantine at 2,5,10,20,30,40 and 60min were (1) 13.5,15.7,34.0,64.8,81.9,91.4 and 95.4 at 70℃;(2) 13.2,20.5,40.1,70.0,88.2,94.5 and 95.6 at 80℃;(3) 15.6,22.9,43.7,74.3,87.2,93.4 and 96.1 at 90℃;and (4) 20.5,25.8,45.3,81.1,92.2,95.6 and 96.0 at 100℃.The other parameters were;n =1;k=0.053,0.061,0.063 and 0.076 L/min at 70℃,80℃,90℃ and 100℃,respectively;Ea=12.38 kJ/L;t1/2=13.11,11.45,11.05 and 9.07min at 70℃,80℃,90℃ and 100℃,respectively.The mean labeling yield increased with temperature and time,optimized at 100℃ and 40-60min.The concentration of 99mTc-N-ethyl-N2S2-Memantine was larger than that of Na99mTcO4,so n=1.The k increased with reaction,hence the accelerated reaction rate at higher temperatures.The labeling reaction was not so difficult because of the low Ea.The t1/2 decreased with increasing reaction temperature,hence the acceleration of labeling reaction.展开更多
基金supported by the Innovation Fund for Technology Based Firms (06C26213201075)National High Technology Research and Development Program of China (863 Program) (2008AA102415)
文摘A competitive indirect time-resolved fluoroimmunoassay(TRFIA) was developed for detection of zearalenone(ZEN) in cereals,in which ZEN conjugated to bovine serum albumin(BSA) is used as solid-phase antigen.A competitive indirect TRFIA was conducted by simultaneously incubating ZEN in standard or extracted samples with anti-ZEN monoclonal antibody over ZEN-BSA coated plates,and then determining the bound ZEN monoclonal antibody with goat anti-mouse europium conjugate.Samples were extracted with methanol/water...
基金Supported by the National Natural Science Foundation of China (No.20801024)Wu Jieping Medical Found(No.32067500615)
文摘A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in conditions of 0.1 mg SnCl2.2H2O at pH 6.0 and 99TcmO4? in aqueous solution for 20 min at room temperature. The labeling yield and radiochemical purity of 99Tcm-PIDP are both higher than 95%. The biodistribution results show that the bone uptake is up to 8.47% ID/g which is the maximum of bone uptake at 30 min after injection of 99Tcm-PIDP in mice. The pharmacokinetic parameters can be estimated from the exponential equation of C=59.565e-11.307t+2.069e-1.211t. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-PIDP. The results indicate that 99Tcm-PIDP has highly selective uptake in the skeletal and low uptake, rapid clearance in soft tissues, so it would be a potential novel bone imaging agent.
基金supported by grants from the National Natural Science Foundation of China(81471736,81671760 and 81873910)Scientific Research Transformation Special Fund of Heilongjiang Academy of Medical Sciences(2018415)Scientific Research Project of Health and Family Planning Commission of Heilongjiang Province(CR201807)
文摘Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value(SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer(CRC) in mice. Methods: Colorectal liver metastases(CRLM) xenograft models were established by injecting tumor cells(LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. ^(18)F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^(18)F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the ^(18)F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1 α(HIF-1 α) and serum starvation-induced glucose transporter 1(GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, ^(18)F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between ^(18)F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ^(18)F-FMISO SUVmax ratio and HIF-1 α or GLUT-1 expression in tumor-bearing tissues. Conclusions: ^(18)F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.
基金Supported by Jiangsu Province’s Key Medical Talents Program(No.RC2007097)Natural Science Foundation of Jiangsu Province,China(No.BK2010154)Science Foundation of Health Department of Jiangsu Province(No.H201226)
文摘Asialoglycoprotein receptor(ASGP-R)is a hepatic membrane receptor that uniquely exists on the surface of mammalian hepatocytes,and has been used as target of liver functional imaging agents for many years.We labeled the Galactosyl-neoglycoalbumin(NGA)with 18F to get a PET molecular probe 18F-FB-NGA and evaluated its ability as a liver functional PET imaging agent.The 18F-FB-NGA was prepared with NGA by conjugation with Nsuccinimidyl-4-18F-fluorobenzoate(18F-SFB)and purified with PD-10 desalting column.The radiolabeling yield and radiochemical purity of 18F-FB-NGA were determined by radio-HPLC.Starting with 18F-F–,the total time for 18F-FB-NGA was about 120±10 min.The decay-corrected radiochemical yield is about 25–30%.The radiochemical purity of purified 18F-FB-NGA was more than 98%.Labeled with 185–1850 MBq 18F-SFB,the specific activity of 18F-FBNGA was estimated to be 7.83–78.3 TBq/mmol.Biodistribution of 18F-FB-NGA in normal mice was investigated after injection through the tail vein.The results showed that the liver accumulated 39.47±3.42 and 12.12±6.11%ID/g at 10 and 30 min after injection,respectively.Dynamic MicroPET images in mice were acquired with and without block after injection of the radiotracer,respectively.High liver activity accumulation was observed at 5 min after injection in normal group.On the contrary,the liver accumulation was significantly lower after block,indicating the specific binding to ASGP-R.18F-FB-NGA is probably a potential PET liver imaging agent.
基金support from the National Natural Science Foundation of China(Grant No.:22076069)the Natural Science Foundation of Jiangsu Province(Grant No.:BK20201135)+1 种基金the Major Scientific Research Project of Jiangsu Commission of Health(Grant No.:ZDA2020007)the Science Technology and Development Project of Wuxi(Grant No.:Y20212013).
文摘Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,^(68)Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer ^(68)Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
基金supported by grants from the National Natural Science Foundation of China(81471736 and 81671760)the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(2015BAI01B09)Project of Research Foundation of the Talent of Scientific and Technical Innovation of Harbin City(2016RAXYJ063)
文摘Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.
基金Supported by National Natural Science Foundation,Nos.81171399,51473071,81101077,21401084,81401450 and 81472749Jiangsu Province Foundation,Nos.BE2014609,BE2012622,BL2012031 and BM2012066Wuxi Foundation,No.CSZ0N1320
文摘Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.
基金Supported by National Natural Science Foundation of China (20573048 and 20676051)Natural Science Foundation of Jiangsu Province (BK2008111, BK2008112)Department of Health of Jiangsu Province (H200624)
文摘Technetium-99m-labeled-5-{2-sulfanylethyl-[2-(2-sulfanylethylamino)acetyl]amino}-methyl-2′-deoxy- uridine (99mTc-ANMdU) was reported. The precursor ANMdU was synthesized by six-step reactions and all intermediates were verified with MS and 1HNMR. Using SnCl2 as reducing agent, a labeling reaction was carried out at 100°C for 30 min. The radiochemical purity of the 99mTc-ANMdU was 96.68%. Partition coefficients were 0.92 and 0.70 at pH 7.0 and 7.4 of the phosphate buffer saline, respectively. Biodistribution of 99mTc-ANMdU in normal mice showed that the initial uptake of 99mTc-ANMdU in vivo and the clearance was rapid.
文摘TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99TcmO4 with SnCl2·2H2O in aqueous solution for 10 min at room temperature. Both labeling yield and radiochemical - purity of Tcm-TADP were more than 95%. The biodistribution in rats and bone scan in rabbits were also studied. The 99 uptake of organ was expressed as %ID/g. The results showed that the bone uptake is up to 17.17%ID/g which is the maximum of bone uptake at 30 min after injection of Tcm-TADP in rats, bone-to-muscle and bone-to-blood uptake 99 ratios were 61.32 and 13.21, respectively. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-TADP and clearance in soft tissue was visible. The preparation of 99Tcm-TADP was convenient and 99Tcm-TADP exhibited high uptake in bone, and it would be a potential new bone imaging agent.
基金Supported by National Natural Science Foundation of China (No.81202032)Key University Science Research Project of Jiangsu Province (No. 16KJB320004)+2 种基金Jiangsu Provincial Health and Family Planning Commission Foundation (No.Z201502)Jiangsu Provincial Health and Family Planning Research Projects (No.H2018029)Key Laboratory of Nuclear Medicine of the Ministry of Health, Jiangsu Provincial Key Laboratory of Molecular Nuclear Medicine (No.KF201501)
文摘The interleukin-11(IL-11)and the IL-11 receptorα-subunit(IL-11Rα)have been demonstrated to regulate the invasion and proliferation of tumor cells.Our study intends to evaluate a noninvasive imaging of IL-11Rαexpression in breast tumors using near-infrared(NIR)fluorescent dye Cy7-labeled IL-11 mimic peptide CGRRAGGSC.This work evaluated the IL-11Rαexpression of breast tumor cells and the binding status of this peptide to IL-11Rαin vitro and in vivo by using Western blotting,immunofluorescence staining and near-infrared fluorescence imaging.Our biochemical study showed that IL-11Rαwas overexpressed in breast tumor cells(MCF-7).The cell-binding assay demonstrated specific binding of peptide CGRRAGGSC to MCF-7 cells in vitro.In vivo imaging results showed that NIR fluorescent signals of Cy7-CGRRAGGSC were selectively accumulated in tumor and metabolic organs.While in the blocking experiment,free CGRRAGGSC obviously blocked the concentration of the Cy7-CGRRAGGSC in the tumors.These results suggested that IL-11Rαmay be used as a potential target for noninvasive imaging in IL-11Rαoverexpressed tumors.Furthermore,the imaging agent of near-infrared fluorescent dye Cy7-labeled CGRRAGGSC is suitable for IL-11Rαexpression imaging study in vivo.
基金Supported by National Natural Science Foundation of China(No.30770602)Natural Science Foundation of Jiangsu Province,China(Nos.BK2010157 and BK2011167)
文摘The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stannous fluoride (SnF 2 ) as reducing agent. Biological characteristics of 99m Tc-PQQE include lipophilic and the charge properties were compared to 99m Tc-PQQ. The biodistributions of 99m Tc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99m Tc-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2β) results indicate that the residence time of 99m Tc-PQQE (203.92) in the body is twice as long as 99m Tc-PQQ (100.45). The uptake of 99m Tc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99m Tc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99m Tc-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that 99m Tc-PQQE has some specific targeting to the NMDA receptor.
基金Supported by National Natural Science Foundation of China(Nos.20801024 and 21001055)Natural Science Foundation of J iangsu Province(No.BK2009077)Science Foundation of Health Department of Jiangsu Province(No.H200963)
文摘A novel zoledronic acid derivative,1-hydroxy-2-(2-butyl-1H-imidazole-1-yl)-ethylidene-l,l- diphosphonic acid(BIDP),was synthesized and labeled with ^(99)Tc^m.The detailed kinetic study on the labeling reaction between BIDP and ^(99)Tc^m was carried out.The results indicated that the reaction rate constants k were 0.0258,0.0268, 0.0305,0.0323,0.0351 and 0.0384 min^(-1)at 0℃,5℃,10℃,15℃,20℃and 25℃,respectively.From the Arrhenius equation k=A·e^(-E_Δ/(RT)),the activation energy E_a of the labeling reaction was calculated to be 10.45 kJ/mol.And the correlation between k and temperature(T)was also deduced as In k=-1258.8×(l/T)+0.9531.In addition,it was found that in order to get a high radiolabeling yield(RLY)(>90%),the reaction temperature must be up to 12℃.
基金Supported by the Society Development Fund of Jiangsu Province (No.BS94012)
文摘To evaluate the clinical value of combined determination of serum PGⅠ, PGⅡ and GAS for early diag-nosis of gastric cancer, the serum levels of PGⅠ, PGⅡ and GAS in 190 healthy controls and 129 patients with gas-tric disorders were measured by RIA. The 129 patients include 68 cases of gastric cancer. The results showed that the serum levels of PGⅠ and PGⅠ/PGⅡ ratio in gastric cancer patients were obviously lower than those in healthy controls, while comparing with controls, the serum GAS levels were significantly higher. The diagnostic accuracy of the determinations for gastric cancer was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) levels of serum PGⅠ, PGⅠ/PGⅡ ratio and GAS were 0.833, 0.842 and 0.851, respec-tively. As serum PGⅠ or PGⅠ/PGⅡ ratio or GAS were combined, the sensitivity and specificity of determination for gastric cancer diagnosis were 94.2% and 73.4%, respectively. All these results indicated that the combined deter-mination of serum PGⅠ, PGⅡ and GAS levels may be used as a tool for primary screening of gastric cancer.
基金Supported by National Natural Science Foundation(No30770602)Jiangsu Natural Science Foundation(No BK2008111)
文摘The pharmacologic characteristics of ^(99)Tc^m-N-ethyl-N_2S_2-memantine,an NMDA receptor imaging agent,was investigated.It was prepared by a one-step reaction from N-ethyl-N_2S_2-memantine.The affinity and specificity were determined by radio-ligand receptor binding assay(RRA).Biodistribution in vivo in mice was performed.The results showed that ^(99)Tc^m-N-ethyl-N_2S_2-memantine bound to a single site on NMDA receptor with a K_d of 584.32 nmol/L and a B_(max)of 267.05 nmol/mg.A competitive analysis showed that such specific binding could be inhibited by specific inhibitors of NMDA receptor,such as ketamine and(+)-MK-801.The biodistribution exhibited rapid uptake and favorable retention in mice brains.The major radioactivity was metabolized by the hepatic system.A two-compartment model of C=4.49e^(-0.083t)+ 1.42e^(-0.0016t)was established,and the half life was 8.35 min in blood.In conclusion,the new radio-ligand ^(99)Tc^m-N-ethyl-N_2S_2-Memantine has a moderate affinity and specific binding to NMDA receptor,and can easily cross the blood-brain barrier(BBB).Therefore,it may be a potential NMDA receptor imaging agent.
基金ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (No.10576030 and No.10576016) and the National Basic Research Program of China (No.61337).
基金Supported by National Natural Science Foundation of China(Nos.81271516 and 81371625)Program of Shanghai Science and Technology Commission(Nos.13JC1401503 and 14DZ1930402)+1 种基金Shanghai Municipal Health and Family Planning Commission(No.2013313)Exchange Programme Foundation of Doctoral Student under the Office for Graduate Medical Education,Fudan University
文摘Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimer's disease(AD). The existence of neurofibrillary tangles(NFTs) consisting of tau protein are one kind of the pathological features of AD, and its level of severity is correlated with the stage of AD.However, no clinically approved positron emission tomography(PET) probe is currently available for selective imaging of neurofibrillary tangles on patients. In this paper, we report our studies on biological characteristics of [18F]-THK523 as a novel tau imaging probe. With low molecular weight, [18F]-THK523 is stable, electrically neutral, lipophilic and non-mass concentration-dependent. Preliminary biological studies have shown the excellent properties of [18F]-THK523 as brain imaging tracer for further research.
基金Supported by National Natural Science Foundation of China(Nos.81271516 and 81371625)Program of Shanghai Science and Technology Commission(Nos.13JC1401503 and 14DZ1930402)+1 种基金the exchange program fund of doctoral student under the office for Graduate Medical EducationFudan University and Shanghai Municipal Health and Family Planning Commission(No.2013313)
文摘Extensive accumulation of neurofibrillary tangles(NFTs)consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer's disease.However,no PET probe is currently available for selective detection of NFTs in the living human brain.[^(18)F]-THK523 was developed as a potential in vivo imaging probe for tau pathology.In this paper,we report a new protected precursor,2-((2-(4-((tert-butoxycarbonyl)amino)phenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(THK-7),instead of2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(BF241),and an improved automated radiosynfhesis of[^(18)F]-THK523 and the study on chemical kinetics of the labeling reaction of[^(18)F]-THK523,with high-yield(70±5%,n=6,decay-corrected to end of bombardment),and high radiochemical purity(>90%)and specific activity(2.5±0.5Ci/umol)from protected precursor on fully automated module at the end of radiosynthesis(45-55 min).The chemical kinetics for[^(18)F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.
基金Supported by the National Natural Science Foundation of China (30970844)the Outstanding Medical Professionals Foundation of Jiangsu Province (RC2011096)Natural Science Foundation of Jiangsu Province of China (BK2010155)
文摘This work was to develop a semi-automated synthesis of 18F-9-fluoropropyl-9-desmethyl-DTBZ (18F-FP-DTBZ) and validate its potential as a vesicular monoamine transporter 2 (VMAT2) ligand.18F-FP-DTBZ was synthesized by a semi-automated procedure in a 21-35% yield without decay correction and with a radiochemical purity of >98%.Bioistribution in rats exhibited a favorable brain uptakes of the ligand (0.31±0.04 ID% at 60min post injection,n=8).The highest radioactivity located in VMAT2 enriched striatal tissue.The target-to-nontarget ratio (striatum/cerebellum,ST/CB) was 4.81±0.84.Blocking studies implied that striatum uptake could be blocked by DTBZ (a VMAT2 inhibitor) but could not by CFT (a dopamine transporter inhibitor).MicroPET imaging with 18F-FP-DTBZ in normal rats gave high quality images in which high radioactivity were observed in the striatal tissue.Time-and-activity curves revealed good retention in the target (striatum) and rapid clearance in the background (cerebellum),which resulted in a maximum ST/CB ratio of 5.08±0.81 (n=3) in 80-120min.By contrast,the 6-hydroxydopamine unilateral lesioned rats gave asymmetrical striata images with higher 18F-FP-DTBZ concentration on the unlesioned side (unlesioned-ST/CB=5.21±0.38,n=3) than the lesioned (lesioned-ST/CB=2.34±0.51).The results validated that 18F-FP-DTBZ is a favorable PET ligand binding to VMAT2.
基金Supported by the National Natural Science Foundation of P. R. China (30570518)High Technology Research and Development Program of Jiangsu Province of China (BG2007603)Science Foundation of Health Department of Jiangsu Province of China (H200401)
文摘This work was to investigate the pharmacologic characteristics of 18F-FECNT (2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane) as a dopamine transporter (DAT) PET imaging agent. Its partition coefficients were determined in n-octanol and phosphate buffer (PB) (pH 7.0 and pH 7.4). 6-Hydroxydopamine (6-OHDA) left-sided lesioned Parkinsonian rats were established and validated by rotational behavior tests. Biodistribution in vivo in mice, autoradiography in normal and hemi-Parkinsonian rat brains, and toxicity test were performed. The results showed that partition coefficients were 34.14 (pH 7.0) and 56.41 (pH 7.4), respectively. Biodistribution exhibited rapid uptake and favorable retention in the mice brains. The major radioactivity was metabolized by the hepatic system. The autoradiography showed that 18F-FECNT was highly concentrated in striatum, and that the left and the right striatal uptake were symmetrical in normal SD rat brains. In left-sided lesioned PD rat brains, the striatal uptake of 18F-FECNT bilaterally decreased in comparison with normal rats. No significant uptake was visible in the 6-OHDA lesioned-sided striatal areas. The results demonstrated that 18F-FECNT binds to DAT was specific. Toxicity trial displayed that the acceptable dose per kilogram to mice was 625 times greater than that to human. These indicate that 18F-FECNT is a potentially safe and useful DAT PET imaging agent in the brain.
基金Supported by the Jiangsu Natural Science Foundation (BK2008111,BK2010157)the National Natural Science Foundation of China (30770602)
文摘In this work,a calculation method of chemical kinetics was established for labeling reaction of 99mTc-N-ethyl-N2S2-memantine,a potential NMDA receptor imaging agent prepared in our laboratory.Four groups of vials (3 vials per group) were added with 0.02 mL (1 mg/mL) N-ethyl-N2S2Memantine,0.08 mL (40 mg/mL) GH,0.05 mL (10 mg/mL) EDTA-2Na,0.035 mL (2 mg/mL) SnF2,0.8 mL phosphate buffer(1mol/L,pH 6.5) and 37 MBq Na99mTcO4.The vials were incubated at 70℃,80℃,90℃ or 100℃.Samples were taken with capillary from the vials at 2,5,10,20,30,40 and 60min.Labeling yields were determined by TLC.Order of reaction n,rate constant k,activation energy Ea and half life t1/2 of labeling reaction were calculated with the kinetics software we compiled.Mean labeling yields of 99m Tc-N-ethyl-N2S2-memantine at 2,5,10,20,30,40 and 60min were (1) 13.5,15.7,34.0,64.8,81.9,91.4 and 95.4 at 70℃;(2) 13.2,20.5,40.1,70.0,88.2,94.5 and 95.6 at 80℃;(3) 15.6,22.9,43.7,74.3,87.2,93.4 and 96.1 at 90℃;and (4) 20.5,25.8,45.3,81.1,92.2,95.6 and 96.0 at 100℃.The other parameters were;n =1;k=0.053,0.061,0.063 and 0.076 L/min at 70℃,80℃,90℃ and 100℃,respectively;Ea=12.38 kJ/L;t1/2=13.11,11.45,11.05 and 9.07min at 70℃,80℃,90℃ and 100℃,respectively.The mean labeling yield increased with temperature and time,optimized at 100℃ and 40-60min.The concentration of 99mTc-N-ethyl-N2S2-Memantine was larger than that of Na99mTcO4,so n=1.The k increased with reaction,hence the accelerated reaction rate at higher temperatures.The labeling reaction was not so difficult because of the low Ea.The t1/2 decreased with increasing reaction temperature,hence the acceleration of labeling reaction.