Preparation and preliminary biological evaluation of 99mTc-ANMdU

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.     

Preclinical evaluation on ~(125)I-BMIPP

The biodistribution of 125I-BMIPP and the variation of myocardial uptake of 125I-BMIPP using the metabolic intervention drug were reported. Myocardial uptake of the 125I-BMIPP in rats showed a peak of 5.70ID%/g at 2 min. The ratios of myocardium to blood, to liver and to lung at 30 min were 3.40, 2.64 and 2.88 respectively. The initial elimination half time of 4.0 min in rabbits was in accordance with the half elimination time of free fatty acid from blood. Myocardial uptake of 125I-BMIPP in the group of glucose-insulin was significantly increased (p<0.05) than those of the normal control. In vivo and in vitro binding test for 125I-BMIPP to HSA showed a rather constant level of activation up to 2 h. Partition coefficients (1gP) were 1.93 and 1.68, respectively.     

Preparation and biodistribution of ^99Tc^m-PIDP as bone imaging agent

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 SnCI2.2H2Cl2·2H2O 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.     

99Tcm-DTPA-Folate的制备及其荷瘤裸鼠体内分布

制备了99Tcm-DTPA-Folate并对其在荷瘤裸鼠的体内分布进行了初步探索.将叶酸(Folate)与DTPA连接,合成DTPA-Folate,再用99Tcm标记,考察标记物的纯度和稳定性,并进行荷人SGC-7901胃癌肿瘤裸鼠的体内分布特性研究.结果表明,99Tcm-DTPA-Folate的标记率＞98%.标记物室温放置4h,放化纯度＞90%.裸鼠腹腔注射99Tcm-DTPA-Folate后8h,肿瘤与周围肌肉的含量比值高达7.51.     

新型骨显像剂99Tcm-ZL的制备和动物实验研究

以氯化亚锡为还原剂、用99Tcm标记唑来膦酸(ZL)制得99Tcm-ZL,研究了SnCl2·2H2O和ZL的用量以及溶液pH对标记率的影响,在pH=3-9、ZL的用量大于2mg和SnCl2·2H2O的用量大于40μg时,室温反应8min,可获放化纯和标记率大于90%的99Tcm-ZL,标记后6h内放化纯度保持不变.并对99Tcm-ZL的小鼠体内分布和兔显像进行了研究.小鼠体内生物分布表明,静脉注射后30min时,骨摄取达13.45%ID/g,am骨/肌和am骨/血分别达到28.01和16.96;兔显像表明,静脉注射75min后,即可获得清晰的骨显像.研究表明,99Tcm-ZL是一种稳定性好、制备简便、值得进一步深入研究的骨显像剂.     

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.     

Preparation and primary biological evaluation of novel nitrido-Re complexes/lipiodol

Two new nitrido-¹⁸⁸Re complexes were prepared by a modified method in high yield. These complexes were stable in vitro. The biodistribution in normal mice showed that these nitrido-¹⁸⁸Re complexes could accumulate in liver and dissipate quickly from almost all organs. TAE was performed with the use of lipiodol solutions of two complexes to rabbit VX2 liver tumor models. SPECT images showed that the two lipiodol solutions could remain in tumor for about 9 h (¹⁸⁸ReN-NEPTDD/lipiodol) and 12 h (¹⁸⁸ReN-NEMMPTDD/lipiodol), respectively.     

99Tcm-HYNIC-β-Ala-BBN（7-14）NH2的制备及其初步评价

99mTc-HYNIC--Ala-BBN(7-14)NH2 was prepared by choosing Tricine and EDDA as coligands, and the in vitro stability and biodistribution were compared for these two compounds. ITLC and HPLC analyses showed that the labeling yield of both compounds was more than 95%, and the radiochemical purity (RCP) after purification of Sep-Pak C18 cartridge was more than 99%. Both compounds showed pretty good stability in saline and fetal bovine serum, but cysteine challenge assay showed that the stability of 99mTc- HYNIC(EDDA)--Ala-BBN(7-14)NH2 was much better than 99mTc-HYNIC (Tricine)--Ala-BBN(7-14)NH2, with the RCP was more than 95% and less than 90%, respectively, at 24 h incubation at 37. Pattern of blood clearance of 99mTc-HYNIC(EDDA)--Ala-BBN(7-14)NH2 and 99mTc-HYNIC(Tricine)--Ala -BBN(7-14)NH2 was defined as two-compartment model, with T1/2冄 calculated to be 0.27 min and 1.55 min, and T1/2円 calculated to be 18.1 min and 29.7 min, respectively. Biodistribution revealed that the %ID/g of 99mTc-HYNIC(Tricine)- -Ala-BBN(7-14)NH2 was higher than that of 99mTc-HYNIC(EDDA)--Ala- BBN(7-14)NH2 for all of tissues at all time points of experiment; The uptake in kidneys for both compounds was relatively high, as the uptake in livers and intestines for 99mTc-HYNIC(Tricine)--Ala-BBN(7-14)NH2 was significantly higher than 99mTc-HYNIC(EDDA)--Ala-BBN(7-14)NH2, that meant that 99mTc-HYNIC(EDDA)--Ala-BBN(7-14)NH2 was mainly excreted through kidneys, while 99mTc-HYNIC(Tricine)--Ala-BBN(7-14)NH2 was excreted through both kidneys and hepatobiliary system. The above data demonstrated that 99mTc-HYNIC(EDDA)--Ala-BBN(7-14)NH2 possessed better chemical and biological properties.     

四种~(99m)Tc标记的乙撑-双(半胱胺酸酯)生物效应比较

本文对四种不同长度碳链烷基酯ECD[N,N′-乙撑-双(L-半胱胺酸乙酯)]衍生物的生物效应进行了比较,研究结果表明,烷基碳链的长度与它们各自的脂溶性、血浆蛋白(HSA)的结合率、脑摄取量呈正相关,但与脑清除速度呈负相关。注射后10s,~(99m)Tc-MCD、~(99m)Tc-ECD、~(99m)Tc-PCD和~(99m)Tc-BCD在大鼠脑的浓度(％I.D/g)分别为0.45、0.59、0.96和0.68。由猴的全身显像所见,注药后1.5h脑药物浓度分别为1.3、3.1、3.2和2.2(％I.D),肝内的放射性浓聚最高,经代谢有较大部分由肾排出。     

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。     

Preparation and primary biological evaluation of novel nitrido-188Re complexes/lipiodol

Two new nitrido-188Re complexes were prepared by a modified method in high yield.These complexes were stable in vitro.The biodistribution in normal mice showed that these nitrido-188Re complexes could accumulate in liver and dissipate quickly from almost all organs.TAE was performed with the use of lipiodol solutions of two complexes to rabbit VX2 liver tumor models.SPECT images showed that the two lipiodol solutions could remain in tumor for about 9 h (188ReN-NEPTDD/lipiodol) and 12 h (188ReN-NEMMPTDD/Iipiodol),respectively.     

Biodistribution and pharmacokinetics of ^99mTc—CQDO and ^99mTc—CQDO—MeB for new myocardial imaging agent

A comparison of ~(99m)Tc- CQDO and ~(99m)Tc-CQDO-MeB has been made for biodistribution and pharmacokinetics. ~(99m)Tc-CQDO and its adducts of methaneboronic acid ~(99m)Tc-CQDO-MeB were prepared by the reduction of Na~(99m)TcO_4 with SnCl_2·2H_2O in aqueous solution. Radiochemical purity of ~(99m)Tc-CQDO and ~(99m)Tc-CQDO-MeB determined by TLC were over 95% after extraction. Biodistributions of ~(99m)Tc-CQDO and ~(99m)Tc-CQDO-MeB in mice demonstrated that both of them could be easily absorbed by myocardium, and the peak uptake of each were 10.83±2.2% ID/g and 11.84±1.69%ID/g, respectively. ~(99m)Tc-CQDO showed rapid clearance from myocardial tissue while ~(99m)Tc-CQDO-MeB had long retention in heart muscle. The myocardial uptake of ~(99m)Tc-CQDO was only 5.88±1.66%ID/g at 10 min. and the uptake of ~(99m)Tc-CQDO-MeB was 7.42±0.17%ID/g at 60 min. The elimination of each from blood has a biexponential pattern, the first T_(1/2) is 1.38 and 1.5 min, respectively. The partition coefficient of ~(99m)Tc-CQD     

Preparation of ^99mTc-PQQE and preliminary biological evaluation for the NMDA receptor

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.     

Synthesis and biological evaluation of 18F-FB-NGA as a hepatic asialoglycoprotein receptor PET imaging agent

Abstract 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 N- succinimidyl-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-F/3 -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 -FB- NGA was estimated to be 7.8-78.3 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. J SF-FB-NGA is probably a potential PET liver imaging agent.     

Preparation and preliminary evaluation of [^55Co]（II）vancomycin

Co-55 （t1/2=17.53 h） was produced by 150 uA irradiation of a natural nickel target using 15 MeV protons. It was separated from the irradiated target material by two ion exchange chromatography steps with a radiochemical yield of 〉95% and was used for the preparation of [^55Co]vancomycin （[^55Co]VAN）. Optimization studies were performed using Co-57 due to its longer half-life. Cobalt-57 （t1/2=271.79 d） was produced by irradiation of a natural nickel target with 150 pA current of 22 MeV protons. The 57Co was separated from the irradiated target material using a no-carrier-added method with a radiochemical yield of 〉97%. Both products were controlled for radionuclide and chemical purity. The solutions of [^55Co]VAN were prepared （radiochemical yield〉80%） starting with 55Co acetate and vancomycin at room temperature after 30 min. A precise solid phrase extraction （SPE） method was developed using Si Sep-Pak in order to purify/reconstitute the final formulation for animal studies. [^55Co]VAN showed a radiochemical purity of more than 99%. The resultant specific activity was about 1.15 TBq/mmol. It is proved that the tracer is stable in the final product and in presence of human serum at 37℃ up to 24 h. Biodistribution study of [55Co]VAN in normal rats was undertaken for up to 72 h.     

Preparation and preliminary evaluation of [55Co](Ⅱ)vancomycin

Co-55 (t1/2=17.53 h) was produced by 150 μA irradiation of a natural nickel target using 15 MeV protons. It was separated from the irradiated target material by two ion exchange chromatography steps with a radiochemical yield of>95% and was used for the preparation of [55Co]vancomycin ([55Co]VAN). Optimization studies were per-formed using Co-57 due to its longer half-life. Cobalt-57 (t1/2=271.79 d) was produced by irradiation of a natural nickel target with 150 μA current of 22 MeV protons. The 57Co was separated from the irradiated target material using a no-carrier-added method with a radiochemical yield of>97%. Both products were controlled for radionuelide and chemical purity. The solutions of [55Co]VAN were prepared (radiochemical yield>80%) starting with 55Co acetate and vancomycin at room temperature after 30 min. A precise solid phrase extraction (SPE) method was developed using Si Sep-Pak in order to purify/reconstitute the final formulation for animal studies. [55Co]VAN showed a radiochemical purity of more than 99%. The resultant specific activity was about 1.15 TBq/mmol. It is proved that the tracer is stable in the final product and in presence of human serum at 37℃ up to 24 h. Biodistribution study of [55Co]VAN in normal rats was undertaken for up to 72 h.     

A comprehensive study on energy absorption and exposure buildup factors for some essential amino acids, fatty acids and carbohydrates in the energy range 0.015-15 MeV up to 40 mean free path

The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) have been calculated for some essential amino acids, fatty acids and carbohydrates in the energy region 0.015-15 MeV up to a penetration depth of 40 mfp (mean free path). The five parameter geometric progression (G-P) fitting approximation has been used to calculate both EABF and EBF. Variations of EABF and EBF with incident photon energy, penetration depth and weight fraction of elements have been studied. While the significant variations in EABF and EBF for amino acids and fatty acids have been observed at the intermediate energy region where Compton scattering is the main photon interaction process, the values of EABF and EBF appear to be almost the same for all carbohydrates in the continuous energy region. It has been observed that the fatty acids have the largest EABF and EBF at 0.08 and 0.1 MeV, respectively, whereas the maximum values of EABF and EBF have been observed for aminoacids and carbohydrates at 0.1 MeV. At the fixed energy of 1.5 MeV, the variation of EABF with penetration depth appears to be independent of the variations in chemical composition of the amino acids, fatty acids and carbohydrates. Significant variations were also observed between EABF and EBF which may be due to the variations in chemical composition of the given materials.     

Preparation and preliminary evaluation of [^55Co]（II）vancomycin

Co-55 (t1/2=17.53 h) was produced by 150 μA irradiation of a natural nickel target using 15 MeV protons. It was separated from the irradiated target material by two ion exchange chromatography steps with a radiochemical yield of >95% and was used for the preparation of [55Co]vancomycin ([55Co]VAN). Optimization studies were per- formed using Co-57 due to its longer half-life. Cobalt-57 (t1/2=271.79 d) was produced by irradiation of a natural nickel target with 150 μA current of 22 MeV protons. The 57Co was ...     

氚标记23-羟基白桦酸的制备及其在动物体内的评价

制备氚标23-羟基白桦酸(3H-23-HBA),并对其在正常鼠及荷瘤鼠的体内分布进行初步探索。23-HBA经23位氧化、硼氚化钠还原后制得3H-23-HBA,考察了标记物的纯度和稳定性,并在ICR小鼠、接种肝癌HepA肿瘤的小鼠体内研究其生物分布特征。结果显示:(1)所得标记物放射化学纯度>95%,放射性比活度为3.33×105Bq/μg(23-HBA);(2)标记化合物的四氢呋喃溶液在–20℃稳定;(3)小鼠尾静脉注射3H-23-HBA(10mg/kg,3.7×105Bq/只)后,在血中清除慢,血浆中原形药约占60%;(4)小鼠尾静脉注射3H-23-HBA(10mg/kg,3.7×105Bq/只)后,在胆、肝、肠浓聚,消除慢;肿瘤鼠肺、胆中摄取高于正常鼠,尤其是胆,至注射后8h仍高达106.89%±47.4%ID/g。实体瘤与对侧肌肉组织的摄取比约为2。3H-23-HBA纯度高,稳定性好,适用于23-HBA药代动力学研究。