以2-乙基咪唑、5-溴戊酸乙酯和PCl3为原料,合成了一种唑来膦酸衍生物:1-羟基-5-(2-乙基-1H-咪唑-1-基)戊烷-1,1-双膦酸(EIPeDP),将其与放射性元素99mTc(Ⅳ)进行标记形成配合物,研究了EIPeDP用量和反应体系pH值对标记率的影响.结果表明,当pH值为5～6、EIPeDP为5 mg、SnCl2·2H2O为100 μg和Na99mTcO4为92.5 MBq时,可获得满意的标记率和放化纯(均大于97％).标记物99mTc-EIPeDP具有良好的体外稳定性.动物体内实验表明,兔经注射99m Tc-EIPeDP 1 h后获得的骨显像图质量明显优于99mTc-ZL和99mTc-MDP.表明99mTc-EIPeDP是一种制备简便、稳定性好和骨显像性能优异的新型放射显像剂.
参考文献
| [1] | Palma E,Correia J D,Campello M P,et al.Bisphosphonates as Radionuclide Carriers for Imaging or Systemic Therapy[J].Mol Biosyst,2011,7:2950-2966. |
| [2] | Lin J H.Bisphosphonates:A Review of Their Pharmacokinetic Properties[J].Bone,1996,18:75-85. |
| [3] | WU Mingshu,CHEN Ruyu,HUANG You.Progress in Synthesis of Bisphosphonic (ate) Analogues[J].Chinese J Org Chem,2004,24 (5):485-497 (in Chinese).吴明书,陈茹玉,黄有.双膦酸及其酯类化合物的合成研究进展[J].有机化学,2004,24(5):485-497. |
| [4] | HAO Erjun,LIAN Jie,SU Yongxiang.Improved Synthesis of Zoledronate Sodium[J].Chem Reag,2009,31 (5):383-385(in Chinese).郝二军,廉洁,苏永祥.唑来膦酸钠的合成工艺改进[J].化学试剂,2009,31 (5):383-385. |
| [5] | Widler L,Jaeggi K A,Glatt M,et al.Highly Potent Geminal Bisphosphonates:From Pamidronate Disodium (Aredia) to Zoledronic Acid(Zometa)[J].J Med Chem,2002,45(17):3721-3738. |
| [6] | Russell R G G,Croucher P I,Rogers M J.Bisphosphonates:Pharmacology,Mechanisms of Action and Clinical Uses[J].Osteoporos Int,1999,9(2):66-80. |
| [7] | Teixeira F C,Antunes I F,Curto M J M,et al.Novel 1-Hydroxy-1,1-Bisphosphonates Derived from Indazole:Synthesis and Characterization[J].Arkat USA Inc,2009:69-84. |
| [8] | Subramanian G,McAfee J G,Blair R J,et al.Technetium-99m-Methylene Diposphonate:a Superior Agent for Skeletal Imaging:Comparison with Other Technetium Complexes[J].J Nucl Med,1975,16:744-755. |
| [9] | Paes F M,Serafini A N.Systemic Metabolic Radiopharmaceutical Therapy in the Treatment of Metastatic Bone Pain[J].Semin Nucl Med,2010,40:89-104. |
| [10] | Lewington V J.Bone-Seeking Radionuclides for Therapy[J].J Nucl Med,2005,46(1):38S-47S. |
| [11] | Pandit-Taskar N,Batraki M,Divgi C R.Radiopharmaceutical Therapy for Palliation of Bone Pain from Osseous Metastases[J].J Nucl Med,2004,45(8):1358-1365. |
| [12] | Love C,Din A S,Tomas M B,et al.Radionuclide Bone Imaging:An Illustrative Review[J].Radiographics,2003,23:341-358. |
| [13] | WANG Hongyong,LUO Shineng,XIE Minhao,et al.The New Bone Imaging Agent:Preparation and Biodistribution of 99Tcm-ZL[J].Nucl Tech,2006,29:438-441 (in Chinese).王洪勇,罗世能,谢敏浩,等.新型骨显像剂:99Tcm-ZL的制备和动物实验研究[J].核技术,2006,29:438-441. |
| [14] | Datta A,Panwar P,Chuttani K,et al.Synthesis of 99mTc-DOTMP and Its Preclinical Evaluation as a Multidentate Imaging Agent for Skeletal Metastases[J].Cancer Biother Radiopharm,2009,24(1):123-128. |
| [15] | NIU Guosai,LUO Shineng,YAN Xiaohong,et al.The Preparation and Biodistribution of 99 Tcm-EIDP[J].Nucl Tech,2008,31:698-701 (in Chinese).牛国塞,罗世能,严孝红,等.99Tcm-EIDP的制备及生物学分布[J].核技术,2008,31:698-701. |
| [16] | Ogawa K,Saji H.Advances in Drug Design of Radiometal-Based Imaging Agents for Bone Disorders[J].Int J Mol Imaging,2011:1-7. |
| [17] | Asikoglu M,Durak F G.The Rabbit Biodistribution of a Therapeutic Dose of Zoledronic Acid Labeled with Tc-99m[J].Appl Radiat Isot,2009,67(9):1616-1621. |
| [18] | Motaleb M A,Sakr T M.Synthesis and Preclinical Pharmacological Evaluation of 99mTc-TEDP as a Novel Bone Imaging Agent[J].J Label Compd Radiopharm,2011,54:597-601. |
| [19] | Lin J G,Qiu L,Cheng W,et al.Development of Superior Bone Scintigraphic Agent from a Series of 99mTc-Labeled Zoledronic Acid Derivatives[J].Appl Radiat Isot,2012,70:848-855. |
| [20] | Qiu L,Cheng W,Lin J G,et al.Synthesis and Biological Evaluation of Novel 99mTc-Labelled Bisphosphonates as Superior Bone Imaging Agents[J].Molecules,2011,16:6165-6178. |
| [21] | Lin J G,Qiu L,Cheng W,et al.Preparation and in Vivo Biological Investigations on a Novel Radioligand for Bone Scanning:Technetium-99 m Labeled Zoledronic Acid Derivative (IPrDP)[J].Nucl Med Biol,2011,38:619-629. |
| [22] | SU Biquan,SHENG Li.The Phase-transfer Catalysts in Organic Synthesis Reactions[J].Chem Eng,2003,6:67-68 (in Chinese).苏碧泉,盛丽.有机合成反应中的相转移催化剂[J].化学工程师,2003,6:67-68. |
| [23] | HUI Xinping,ZHANG Linmei,ZHANG Ziyi.Application of Phase Transfer Catalysis in Heterocyclic Chemistry[J].Chinese J Org Chem,1999,19 (5):458-467 (in Chinese).惠新平,张林梅,张自义.相转移催化在杂环化学中的应用[J].有机化学,1999,19(5):458-467. |
| [24] | Qiu L,Cheng W,Lin J G,et al.Synthesis and Evaluation of A Series of 99mTc-labelled Zoledronic Acid Derivatives as Potential Bone Seeking Agents[J].J Radioanal Nucl Chem,2013,295:545-552. |
上一张
下一张
上一张
下一张
计量
- 下载量()
- 访问量()
文章评分
- 您的评分：
-
10%
-
20%
-
30%
-
40%
-
50%