摘要
目的探讨^99Tc^m-1-羟基-3-（2-丁基-1皿咪唑-1-基）丙烷-1，1-双膦酸（BIPrDP）用于骨显像的可能性。方法以2-丁基咪唑为原料，经过3步反应得到BIPrDP。以SnCl2为还原剂，在100℃下沸煮BIPrDP钠盐溶液（50mg／ml，100μl）与新鲜淋洗的Na^99Tc^mO4溶液（37．0MBq）混合液30min，制得^99Tc^mBIPrDP。用TLC测定标记率和稳定性。测定^99Tc^mBIPrDP在正辛醇-水中的脂水分配系数（10gP）和在新鲜肝素抗凝的人血血浆中的血浆蛋白结合率。向ICR小鼠尾静脉注射0．2ml（7．4MBq）^99Tc^mBIPrDP，分别在5、10、15、30、60、120和240min时处死小鼠，取其心、肝、脾、肺、肾、骨骼、肌肉、性腺、肠、胃、脑和血液，测其质量及放射性计数，计算％ID／g及骨放射性与各组织中放射性的比值。计算血药清除动力学方程。对新西兰兔静脉注射^99Tc^m-BIPrDP后于不同时间显像。用单因素方差分析方法对不同时间各组织％ID／g进行统计学分析。结果^99Tc^m-BIPrDP的标记率和放化纯均〉95％，在放置6h后仍具有很好的稳定性。^99Tc^m-BIPrDP在pH值为7．0和7．4时的logP分别为-2．396±0．035和-2．242±0．025，^99Tc^m-BIPrDP的血浆蛋白结合率为（47．07±0．05）％。在注射^99Tc^m-BIPrDP30min后小鼠骨摄取达到最大值（19．20％ID／g），且能持久，在4h时为18．98％ID／g。在所有的非靶向性组织中，^99Tc^m-BIPrDP在肾的摄取最高，5min时为24．50％ID／g，4h为5．22％ID／g。其他重要器官普遍摄取较低，在4h时肌肉和脑最低，分别为0．18％ID／g和0．03％ID／g。在5min时^99Tc^m-BIPrDP在血液中的摄取为18．60％ID／g，随后迅速降低，在4h时仅为0．40％ID／g，血药动力学方程为C=9．109e^-0262t＋2．696e^-0.00558t。从药物清除曲线可看出该药在小鼠体内血液清除速率较快，与小鼠体内分布中的血液清除趋势-致。注射^99Tc^m-BIPrDP后1h即可获得清晰的兔骨显影，在其他软组织中摄取低，清除快。各组织不同时间％ID／g差异有统计学意义（F=5．65-859．24，P均〈0．05）。结论^99Tc^m-BIPrDP制备方便，骨显影清晰，是-种较有潜力的新型骨显像剂。
Objective To investigate the feasibility of ^99Tc^m-1-hydroxy-3-（2-butyl-lH-imidazo1-1- yl） propane-1, 1-diphosphonic acid （BIPrDP） as a new bone imaging agent. Methods BIPrDP was synthe- sized by three steps from the raw material 2-butyl-lH-imidazole. 99Tem-BIPrDP were prepared with mixed BIPrDP （50 mg/ml, 100 μl） and freshly eluted Na^99Tc^m O4 （37.0 MBq） in the presence of the reducing a- gent SnC12 （ 1 mg/ml, 100 μ1） at boiling temperature for 30 min. The labeling yield and stability of ^99Tc^m- BIPrDP were measured with TLC. Partition coefficient in octanol-water and plasma protein binding ratio tohuman heparin anticoagulation plasma of ^99Tc^m- BIPrDP was checked. ICR mice were sacrificed at 5, 10, 15, 30, 60, 120 and 240 min after tail vein injection of 0.2 ml （7.4 MBq） freshly prepared ^99Tc^m-BIPrDP. Samples of blood, heart, liver, spleen, lung, kidney, bone, muscle, gonad, intestine, stomach and brain were taken, weighed and the gamma counts measured. The biodistribution of the radiolabeled compound in different organs was calculated and expressed as % ID/g. Bone-to-organ uptake ratios were calculated by the % ID/g values. The kinetics of blood clearance was calculated. Bone imaging was performed in New Zeal- and rabbit after intravenous injection of ^99Tc^m-BIPrDP. One-way analysis of variance was used to analyze the %ID/g at different times points. Results Radiolabeling yield of ^99Tc^m-BIPrDP was more than 95% and the labeled complex was stable at least up to 6 h in vitro. The octanol-water partition coefficients （log P） for ^99 Tc^m-BIPrDP were - 2. 396 ± 0. 035 and - 2. 242 ± 0.025 at pH values of 7.0 and 7.4, respectively. The plasma protein binding rate of 99Tcm-BIPrDP was （47.07 ±0.05 ）%. The bone uptake of ^99Tc^m-BIPrDP in mice reached a maximum of 19.20 % ID/g at 30 rain after injection, and this high level of uptake persisted 4 h later at 18.98 % ID/g. Kidney uptake was highest among all the non-target organs, but decreased from 24.50 % ID/g at 5 min to 5.22 % ID/g at 4 h. The labeling compounds were excreted mainly through the kidneys, and the uptake in other important organs were extremely low. The muscle and brain exhibited the two lowest uptake, with values of 0.18 % ID/g and 0.03 % ID/g at 4 h, respectively. The uptake of blood was 18.60 %ID/g at 5 min,and then decreased rapidly; the uptake was only 0.40 % ID/g at 4 h. The pharmacokinetic equation was C =9. 109e^-0.262t ± 2. 696e^-0.00558t. From the blood kinetic curve, it was con- cluded that the complex ^99Tc^m-BIPrDP eliminated rapidly from the blood, which was consistent with the bio- distribution results in mice. A clear bone image of rabbit was obtained 1 h after the injection of ^99Tc^m- BIPrDP, which suggested that the selectivity of bone absorption was very good. Low uptake and rapid clearance in other soft tissues could be seen from the whole-body images. The % ID/g at different time points was signifi- cantly different （ F = 5.65 - 859.24, all P 〈 0. 05）. Conclusion The preparation of ^99Tc^m-BIPrDP is con- venient and exhibits high uptake in bone, which suggests its potential as a novel bone imaging agent.
出处
《中华核医学与分子影像杂志》
CSCD
北大核心
2012年第5期379-384,共6页
Chinese Journal of Nuclear Medicine and Molecular Imaging
基金
国家自然科学基金（20801024）
江苏省自然科学基金（BK2009077）
江苏省卫生厅科技项目（H200963）
