β甲基对125碘苯代十五烷酸(125I-BMIPP)的初步动物实验

为了解脂肪酸代谢显像剂 β甲基对12 5碘苯代十五烷酸 (12 5I -BMIPP)在动物体内的分布、清除和代谢干预对其心肌摄取的变化等行为 ,进行了12 5I -BMIPP的动物研究。结果显示 ,禁食SD大鼠心肌对12 5I -BMIPP的摄取高 ,最大吸收值为 5 .70 %/ g ,在心肌中滞留 1h都不变 ,至12 0min心肌摄取仍高达 2 .19± 0 .4 2ID %/ g ;30min心 /血、心 /肝和心 /肺比分别为 3.4 0、2 .6 4和 2 .88;12 5I-BMIPP在肝、肺中的摄取低 ,排泄快 ;甲状腺摄取低 ,至 12 0min ,甲状腺摄取值为 0 .0 2ID %/g ;12 5I-BMIPP与小鼠体内、外血浆蛋白结合稳定 ;异常毒性试验合格 ,每千克小鼠接受的量是人的 5 0 0倍 ;pH为 7.0 0和 7.4 0时的分配系数 (logP)分别为 1.93和 1.6 8;代谢干预研究结果显示 ,葡萄糖胰岛素干预组心肌摄取明显升高 ,与对照组相比差异具有极显著的意义。     

对碘苯代十五烷酸的初步动物实验

为了解脂肪代谢代像剂＾１２５Ｉ－对碘苯代十五烷酸（ＩＰＰＡ）在动物体内的分布，清除等行为，进行了＾１２５Ｉ－ＩＰＰＡ动物实验，结果表明，大鼠心肌对＾１２５Ｉ－ＩＰＰＡ的摄取高而快，最大心肌摄取值为４．４ＩＤ％／ｇ，半清除时间Ｔ１／２α＝３．８ｍｉｎ，甲状腺摄取低，至１２０ｍｉｎ，甲状腺摄取值仅为０．００５ＩＤ％／ｏｒｇａｎ。兔血药清除Ｔ１／２α＝２．７ｍｉｎ，＾１２５Ｉ－ＩＰＰＡ与小鼠体内血浆蛋白     

Preclinical pharmacological study on ^125I—IPPA

Myocardial uptake of ^125I-IPPA in rats showed a Peak of 4.4% of injected dose per gram.The half elimination time of myocardium was 3.8min and the maximal uptake of thyroid is only 0.005%ID/organ at 120min.The initial half time of 2.7min in rabbits was obtained from the elimination curve of radioactivity in blood.In vitro binding test for 125I-IPPA to HSA showed rather constant level of activation during two hours.The second peak of extraction was observed in major organs of rats,in rabbits‘ elimination of radioacivity and in binding test for 125I-IPPA to ablumin in vivo.Toxicity trial was up to standard.The tolerance of a mouse to IPPA was 560 times as high as that of a person to IPPA,It demonstrated that ^125I-IPPA could be quickly exptracted by myocardium,and its catabolites were excreted in the urine with almost no iodine loss.All the results were found to agree with the expectations based on the principal metabolic path of phenyl fatty acid.     

Preclinical pharmacological study on 125I-IPPA

Myocardial uptake of ¹²⁵I-IPPA in rats showed a peak of 4.4% of injected dose per gram.The half elimination time of myocardium was 3.8min and the maximaluptake of thyroid is only 0.005%ID/organ at 120min. The initial halftime of 2.7min in rabbits was obtained from the elimination curve ofradioactivity in blood. In vitro binding test for ¹²⁵I-IPPA to HSAshowed rather constant level of activation during two hours.The second peak of extraction was observed in major organs ofrats, in rabbits' elimination of radioactivity and in bindingtest for ¹²⁵I-IPPA to albumin in vivo. Toxicity trial was up tostandard. The tolerance of a mouse to IPPA was 560 times as highas that of a person to IPPA. It demonstrated that ¹²⁵I-IPPA couldbe quickly extracted by myocardium, and its catabolites were excretedin the urine with almost no iodine loss. All the results were found toagree with the expectations based on the principal metabolic path ofphenyl fatty acid.     

Pharmacological studies of dopamine transporter imaging agent 125／131I－β－CIT

To prepare ^125/131I-β-CIT(2β-carbomethoxy-3β-(4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT),the labeling method from tributylstannyl precursor with peracetic acid has been reported in this article.The radiochemical purity(RCP) of the labeled compound was over 95% determined by HPLC and TLC.The stability,partition coefficients were also determined.The pharmacological studies of the imaging agent were performed in rats,mice,rabbits and normal monkey.The ligand showed preferable uptake in rats,mice,rabbits and normal monkey.The ligand showed preferable uptake in brain (1.9%ID/organ in rats and 4.5%ID/organ in mice at 5min).The ratios of striatum/cerebellum,hippocampus/cerebellum and cortex/cerebellum were 29.8,3.97and 4.75 at 6h in rats,and 8.52,2.99 and 3.06 at 6h in mice,respectively.In monkey brain imaging the ratios of striatum/frontal cortex(ST/FC)and striatum/occipital cortex(ST/OC) were 5.14 and 5.97 at 4h.respectively,All of above showed the high affinity of the ligand to DAT,The compound was primarily metabolized in liver because the hepatic uptake was much higher than other organs(75.4%ID/organ at 18h).The half-life of blood elimination was 5min.The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity,which evaluated the safety of the agent.All the results suggest that β-CIT can be used as a potential DAT imaging agent.     

125I标记的羊抗人IgG多克隆抗体在荷人结肠癌裸鼠体内的生物分布及γ显像

采用Iodogen法对羊抗人IgG多克隆抗体(GAHG)进行125I标记,评价其体外稳定性及药代动力学性质,观察125I-GAHG在荷HT-29人结肠癌裸鼠中的生物分布和γ显像,探讨肿瘤细胞分泌的IgG作为靶点进行肿瘤放射免疫显像和治疗的可能性。结果显示,125I-GAHG具有良好的体外稳定性,其血液清除符合二室模型,T1/2α和T1/2β分别为1.19 h和43.99 h。尾静脉给药后,与125I标记的正常羊IgG(125I-GIgG)对照相比,125I-GAHG具有更加明显的肿瘤摄取。瘤体内给药显示125I-GAHG在肿瘤部位具有良好的滞留。在静脉注射后72 h,肿瘤摄取达到最大,为6.71 ± 2.19 %ID/g。靶组织与非靶肿瘤放射性比值(T/NT)随着时间延长逐渐增高。上述结果表明,肿瘤分泌的IgG为肿瘤放射免疫显像和靶向治疗提供了新的靶点和研究思路。     

99mTc标记新型硼酸结构快速心肌灌注显像药物的制备及初步显像评价

^99mTc-TEBO为临床批准的快速心肌灌注显像药物,该药物初始摄取高,但心肌滞留不稳定,为此,本研究通过优化其硼酸结构,分别制备标记物^99mTc-2SP、^99mTc-4LPA及^99mTc-2MDM,制备时间均为30 min,均为无色澄明液体,放化纯度均>95%,分别在健康小型猪体内进行SPECT动态显像,并与99mTc TEBO进行对比。结果表明：^99mTc-TEBO注射后0~5 min,左室心肌快速摄取,但随后心肌放射性迅速洗脱,在10 min时心肌约洗脱至峰值的75%,与心血池放射性浓度比值为1.63。^99mTc-2SP引入2-甲磺酰基吡啶-5-硼酸基后心肌初始摄取高,心肌滞留时间明显延长,心肌洗脱较缓慢,左室心肌均清晰显影,在第10 min时心肌摄取仍可保持峰值的95%,与心血池放射性浓度比值为3.75,明显高于^99mTc-TEBO。而另外两种显像剂^99mTc-4LPA和^99mTc-2MDM在注射后15 min内显像不理想。因此,^99mTc-2SP是有潜力的心肌灌注显像药物。     

18F标记哒嗪酮类似物的制备及其在小鼠体内的生物分布

设计并合成了一种18F标记哒嗪酮类似物：2-特丁基-4-氯-5-(2 氟[18F]乙氧基)-2H-3-哒嗪酮（18F-FP2）,通过生物分布实验评价了其用于心肌灌注显像的可行性。18F-FP2的总制备时间为70～90 min,校正后的放化产率为53.0%±5.2%,放化纯度>98%;18F-FP2为脂溶性化合物,在水溶液中可稳定放置3 h以上。生物分布实验结果显示,18F-FP2在肝、肺中初期摄取高,注射后2 min分别为（14.53±2.36）%ID/g和（33.69±10.79）%ID/g,但清除很快,注射后15 min,其肝、肺的清除率已分别达57.7%和86.2%。18F-FP2的心肌摄取较低,最高摄取值为（4.09±0.53）%ID/g（注射后2 min）。这可能因标记侧链上未带苯环造成的,说明哒嗪酮侧链的芳环结构对心肌的摄取与滞留有较大影响。     

脑显像剂IMP的放射性碘标记及动物实验

文章报道了对本校合成的RS-N-Isopropyl-P-Iodoamphetamine进行~(125)I标记和动物实验的初步结果。我们采用水热法进行同位素交换反应,在Cu(II)和过量还原剂存在的条件下,可以方便地获得高标记率的~(125)I-IMP。经萃取纯化后,放化纯度>98%;游离~(125)I<1%。测定了在大鼠体内静脉注射~(125)I-IMP的分布,结果表明,~(125)I-IMP具有脑摄取率高、脑与血的比值大、在脑贮留时间长等优点,是一种有用的新型脑显象剂。     

Preclinical pharmacology study of neutral myocardial imaging agent ^99mTcN（NOEt）2

To explore the biological properties of a new neutral myocardial imaging agent ^99mTcN(NOEt)2,preparation and characterization of ^99mTcN(NOEt)2, kinetics of blood-drug clearance in rabbits,biodistribution in rats,test of undue toxicity in mice and myocardial imaging in dogs were performed and volunteer imaging,Radiochemical purity of 99m TcN(NOEt)2 was over than90% and stable for 6 hours at room temperature.Blood disappearance was analyzed with biexponential model,T1/2(α)=2.53min,T1/2(β)=330min and Cl=378mL/h were obtained.Biodistribution studies demonstrated that ^99mTcN(NOEt)2 localized selectively in myocardium of rats.Cardiac uptake were 2.79,2.25,2.00 and 1.88%ID/organ at 5,30,60 and 90min of postinjection,respectively.The heart-to-lung activity ratio was 1.16 at 60 min.Images showed that pulmonary uptake decreased faster than cardiac uptake in a dog.The mean heart-to-lung activity ratios in a dog were 1.69,2.40and 2.55at 10,30and 60min of postinjection,respectively.The heart was distinguishable on scans at 30min.Whole body imaging showed that cardiac uptake was 2.82%ID at 90min,but hepatic uptake was 30%ID and remained constant.The test of undue toxicity showed that the dose received by mice was 614 times as by human.Volunteer imaging suggests ^99mTcN(NOEt)2 redistribution with time.^99mTcN(NOEt)2 exhibited favorable stabilities,biological properties and safety,It is worth for further studying in human.     

红景天苷的碘标记及其在小鼠体内的分布

通过131碘标记红景天苷以探索红景天苷在神经母细胞(SH-SY5Y)中的摄取及在小鼠体内的代谢分布.采用氯胺-T法对红景天苷进行131碘标记;以聚酰胺薄膜为支持介质、V三氯甲烷:V甲醇:V丙酮:V水=6:3:1:1的下层液为展开剂,测定标记率及标记物放化纯;分析神经母细胞SH-SY5Y及肿瘤细胞MCF-7对131I-红景天苷的摄取;KM小鼠尾静脉注射131I-红景天苷(1.85 MBq/只,n=5),于5、10、30、60、120、240 min分别取心、肝、肺、肾、脾、肌、骨、脑、肠、血,称重、计数,计算每克组织百分注射剂量率(%ID/g).结果表明,131I-红景天苷标记率达98%,其放化纯在1、4、20 d分别为98.5%、97.3%、97.1%;SH-SY5Y对131I-红景天苷基本无摄取,在0.5-4 h内摄取维持在0.035%左右,而MCF-7则为0.1%;131I-红景天苷在体内主要通过肝代谢、肾排泄,其中肝和肾5 min%ID/g组织分别为7.71%和11.32%,4 h则分别下降为0.36%和0.3%;血液中清除也较快,5 min时为6.41%,4 h为0.35%;在脑中虽分布较少,但清除较慢,5 min时为0.27%,4 h为0.11%;在心、肺、脾、肌、骨及肠中分布不多.结论是,碘标红景天苷标记率高,标记物稳定;神经母细胞对131I-红景天苷基本无摄取.     

125I-interleukin-8 radiolabelling and in vivo distribution

1 Introduction Interleukin-8(IL-8) is expressed as a 99 aminoacid protein by monocytes, endothelial cells, fibro-blasts and many cell types of epithelial origin. Fol-lowing cleavage of a signal peptide and further prote-olytic processing at the ami…     

123I标记侧链脂肪酸BMIPP的研制

采用新生态Ｃｕ（Ｉ）催化碘同位素交换反应制备了＾１２３Ｉ－ＢＭＩＰＰ。经高效液相色谱法分离纯化,产品放射化学纯度＞９５％,放化产率为３０％－４０％,经细菌检验,热原检验证明无菌、无热原。动物体内分布显示心肌摄取＾１２３Ｉ－ＢＭＩＰＰ快速、存留时间长,与周围临近组织的放射性比值高,适合于ＳＰＥＣＴ代谢显像。     

Radioiodine-labeling of EGCG and Its Biodistribution in Mice

To establish the ¹²⁵I-EGCGlabeling method and investigate the biodistribution of ¹²⁵I-EGCG inmice, ¹²⁵I-EGCG was prepared by Iodogen solid labeling method, andwere isolated and purified by Sephadex-G25 agarose, The labeling yield andradiochemical purity of ¹²⁵I-EGCG was analyzed by polymide TLC. Thelabeling yield of ¹²⁵I-EGCG was 89.4% and its radiochemicalpurity(RCP) were 96.4%. The Biodistribution of ¹²⁵I-EGCG in mice wasmeasured at different times after caudal vein injection with 185 kBq for eachmice. The biodistribution in mice demonstrated that ¹²⁵I-EGCG wasdistributed into broad organs and tissuuues, especially in the Stomach, Smallintestine and Submaxillay gland, and the biggest uptake of ¹²⁵I-EGCGin there organs was 15.92、5.83and 11.56 %ID·g^-1respectively at 15 min post injection. In addition, ¹²⁵I-EGCG wascleared out from blood guickly, and theuptake of ¹³¹I-EGCG in blood was 11.95 at 5 min, anddecreased to 1.25 at 4 h post injection. Therefore, ¹²⁵I-EGCG wasstable and it was metabolized mainly in Stomach, Small intestine, Submaxillaygland, worthy of further investigation to trace the compound in vivo and invitro.     

~(125)I-OxLDL-Ab在正常小鼠及动脉粥样硬化动物模型体内的生物分布

分别采用高效液相色谱法、紫外分光光度法对OxLDL-Ab进行定性、定量分析,评价~(125)I-OxLDL-Ab在正常动物和动脉粥样硬化模型动物的体内分布。正常动物采用昆明小鼠,模型采用载脂蛋白E基因敲除的小鼠(apolipoprotein E-deficient mice,ApoE~(-/-))。高效液相色谱条件为:磷酸缓冲液(PB,0.2 mol/L,pH=7.4)为流动相,流速1.0mL/min,检测波长220nm;紫外分光光度法测得蛋白浓度的标准曲线为:y=0.664 5x-0.008 3,r2=0.999 7。~(125)I-OxLDL-Ab在正常小鼠体内分布实验结果表明:除甲状腺外,各器官的放射性摄取随时间延长而减少,无明显浓集;在注射~(125)I-OxLDL-Ab后1d各器官代谢消除超过2/3,7d后血液中完全清除。~(125)I-OxLDL-Ab在ApoE~(-/-)鼠体内的分布实验中采用w=2%的KI溶液封闭了甲状腺,消除了甲状腺高摄取的影响;靶器官肺有较高放射性摄取,且在注射后4~8h显示出放射性浓集;除血外,其它各器官的靶器官/非靶器官的放射性摄取比值(T/NT)均大于1,其中T/Mu(肌肉)8,显示出~(125)I-OxLDL-Ab对靶器官有一定的选择性。标记抗体的体内靶向性是显像研究中至关重要的一环,要进一步用于动脉粥样硬化早期显像诊断,还需进一步提高靶器官/非靶器官的放射性摄取比值,提高其在体内与其抗原的亲和性。     

Preparation and Biological Evaluation of Novel 18F-labeled Phosphonuim Cation for Myocardial Perfusion Imaging with PET

In order to develop new PET myocardial perfusion imaging agent, a novel¹⁸F labeled phosphonium cation: (3-(［¹⁸F］fluoromethyl)benzyl) tris (2, 6-dimethoxyphenyl) phosphonium salt, ¹⁸F-2, had been designed and prepared. Biological evaluation of¹⁸F-2 had been performed in Kunming normal mice.¹⁸F-2 was obtained by a simple one-pot method and the radiochemical yield was (31±3)%. The total radio-synthesis time was less than 60 min and the radiochemical purity of final radiotracer was more than 95%. The biodistribution of¹⁸F-2 displayed a high heart uptake and good retention. The heart uptake of¹⁸F-2 at 5 and 60 min post-injection were (53.88±7.45)%ID/g and (23.93±3.28)%ID/g, respectively.¹⁸F-2 exhibited low radio-accumulation in non-target tissues and rapid clearance in liver, lung and blood. The heart to liver, heart to lungs and heart to blood ratio values were 3.99, 3.80 and 9.17, respectively. The results indicated that¹⁸F-2 could be as a promising myocardial perfusion imaging agent for PET imaging.     

Biological evaluation on 125I-ADAM as serotonin transporter ligand

ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) is suggested as a promising serotonin transporter (SERT) imaging agent for central nervous system. In this paper, biodistribution studies in rats showed that the initial uptake of 131I-ADAM in the brain was high (1.087%ID at 2 min post-injection), and consistently displayed the highest binding (between 60~240 min post-injection) in hypothalamus, a region known with the highest density of SERT. The specific binding((T/CB)-1) of 131I-ADAM in hypothalamus were 2.94, 3.03 and 3.09 at 60, 120 and 240 min post-injection, respectively. The (T/CB)-1 was significantly blocked by pretreatment with paroxetine, which is known as a serotonin site reuptake inhibitor, while another nonselective competing drug (5HT2A antagonist) Ketanserin, showed no block effect. The rat brain autoradiography and analysis showed that there was a high 131I-ADAM uptake in hypothalamus, the ratio of hypothalamus/cerebellum was significantly reduced from 7.94±0.39 to 1.30±0.56 by pretreatment with paroxetine at 60 min post-injection. Blood clearance kinetics was performed in rats, and the initial half-life of 13.79 min and late half-life of 357.14 min were obtained. The kinetic equation is: C=3.6147e-0.0725t 1.0413e-0.0028t. The thyroid uptake was 0.009% ID and 1.421% ID at 2 min and 120 min post-injection, respectively, suggesting that in vivo deiodination may be the major route of metabolism. Toxicity trial showed that the dose per kilogram administered to mice was 1000 times greater than that to humans, assuming a weight of 50kg. These data suggest that 131I-ADAM may be useful for SPECT imaging of SERT binding sites in the brain.     

The preclinical pharmacological study of dopamine transporter imaging agent ^18F-FP-β-CIT

The paper is to study pharmacologic characteristics of 18F-FP-β-CIT (18F-N-(3-fluoropropyl)-2β-carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18F-FP-β-CIT in aqueous solution was over 95% after standing at room temperature for 4h. Biodistribution displayed rapid uptake in rat brain (1.375 %ID/organ at 5min and 0.100 %ID/organ at 180 min) and the striatal uptake was 1.444, 0.731, 0.397, 0.230 and 0.146 %ID/g at 5, 30, 60, 120 and 180 min, respectively. The values of striatum/cerebellum, striatum /frontal cortex and striatum / hippocampus in rat's brain at 30 min were 3.38, 2.17 and 2.40 respectively. The uptake in striatum can be blocked by β-CFT, suggesting that 18F-FP-β-CIT binds to DAT peculiarly. The compound was rapidly cleared from monkey's blood. The striatal uptake was bilaterally decreased in the left-sided lesioned PD rats, compared with normal control. Brain PET imaging studies in normal monkey showed that 18F-FP-β-CIT was concentrated in striatum. The test of undue toxicity showed that the dose received by mice was 1250 times as by human, which indicates that 18F-FP-β-CIT is very safe. So 18F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity.     

Preparation andBiodistribution of Myocardial Perfusion Imaging Agent 18F-TPT

⁹⁹Tc^m-sestamibi is typically used as amyocardial perfusion imaging agent for SPECT, however, the high uptake of liverand lung compromise the diagnostic accuracy. PET has higher spatial resolutionand quantitative measurement of myocardial tracer uptake. The lipophiliccationic compound, (4-[¹⁸F]fluorophenyl)triphenylphosphoniumion (¹⁸F-TPT)was synthesized as a potential positron emission tomography (PET) myocardialperfusion agent, biodistribution studies in the NH rats and Micro PET/CTimaging studies in the SD rats were performed. Total synthesis time was about 1h and the uncorrected synthesis yield was 2.5%, radiochemical purity was higherthan 99.5%, the product had good stability at room temperature. Biodistributiondata in rats showed high levels of accumulation in the heart with stableretention and rapid blood clearance, Heart-to-liver ratios at 30, 60, 90,and120 min were 33.1, 14.8, 25.7 and 17.3, respectively; Micro PET/CT imagingin the SD rat showed intense cardiac uptake and non-target tissues as liver,lung uptake were washed out quickly. The result show that ¹⁸F-TPT may have potential as amyocardial perfusion imaging agent for PET.     

Preparation and preliminary biological evaluation of 99Tcm-TADP as bone imaging agent

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. 99Tcm-TADP was prepared with 5 mg TADP at Ph 7.0 by joining 99TcmO4 with SnCl2·2H2O in aqueous solution for 10 min at room temperature. Both labeling yield and radiochemical purity of 99Tcm-TADP were more than 95%. The biodistribution in rats and bone scan in rabbits were also studied. The 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 99Tcm-TADP in rats, bone-to-muscle and bone-to-blood uptake 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.