|
|
|
| Design and Development on Tumor Imaging of Nonpeptide Small Molecular Antagonists of Integrin αⅤβ3 |
| LI Ling;ZHANG Chun-li;WANG Rong-fu |
| Nuclear Medicine Department of Peking University First Hospital, Beijing 100034, China |
|
|
|
|
Abstract Integrin αⅤβ3 is significant to tumor angiogenesis, which is necessary for tumor growth and metastasis. So, it’s beneficial for us to make noninvasive visualizations and targeted treatments in tumor patients to detect malignant tumors and inhabit tumor metastasis early by using radiolabeled integrin αⅤβ3 antagonists which have high specificity and affinity to integrin αⅤβ3. This article will focus on the current researches on nonpeptide small molecular antagonists of integrin αⅤβ3 by computerassisted drug design(CADD) to review the nonpeptide antagonists of integrin αⅤβ3 in present progress. Also, it makes an analysis on the applications of radiolabeled small molecular antagonists as probes in tumor imaging.
|
|
Received: 01 January 1900
|
|
|
|
| [1] |
Beer AJ, Schwaiger M. Imaging of integrin alphavbeta3 expression[J]. Cancer Metastasis Rev, 2008, 27(4): 631-644.
|
| [2] |
Liu ZF, Wang F, Chen X. Integrin αⅤβ3 targeted cancer therapy[J]. Drug Development Research, 69(6): 329-339.
|
| [3] |
Dijkgraaf I, Boerman OC. Radionuclide imaging of tumor angiogenesis[J]. Cancer Biother Radiopharm, 2009, 24(6): 637-647.
|
| [4] |
黄云鹏. 整合素αⅤβ3在肿瘤血管生成中的作用[J]. 中国肿瘤, 2007, 16(1): 35-38.
|
| [5] |
张春丽,杨铭,王荣福. RGD肽与整合素αⅤβ3受体结合的构效关系及放射性标记配体的设计[J]. 肿瘤学杂志,15(1): 76-81.
|
| [6] |
刘红洁,王荣福,张春丽,等. 131I标记RGD环肽在荷瘤小鼠体内分布与显像研究[J]. 中国医学影像技术, 2008, 24(1): 131-133.
|
| [7] |
Edwards D, Jones P, Haramis H, et al. 99mTc-NC100692——a tracer for imaging vitronectin receptors associated with angiogenesis: a preclinical investigation[J]. Nucl Med Biol, 2008,35(3): 365-375.
|
| [8] |
Roed L, Oulie I, McParland BJ, et al. Human urinary excretion of NC100692, a RGDpeptide for imaging angiogenesis[J]. Eur J Pharm Sci, 2009, 37(3-4): 79-83.
|
| [9] |
Raguse JD, Gath HJ, Bier J, et al. Cilengitide (EMD 121974) arrests the growth of a heavily pretreated highly vascularised head and neck tumour[J]. Oral Oncol, 2004, 40(2): 228-230.
|
| [10] |
Ruoslahti E, Pierschbacher MD. Arg-Gly-Asp: a versatile cell recognition signal[J]. Cell, 1986, 44(4): 517-518.
|
| [11] |
Wester HJ, Schottelius M, Scheidhauer K, et al. Comparison of radioiodinated TOC, TOCA and Mtr-TOCA: the effect of carbohydration on the pharmacokinetics[J]. Eur J Nucl Med Mol Imaging, 2002, 29(1): 28-38.
|
| [12] |
Chen X, Hou Y, Tohme M, et al. Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor alphavbeta3integrin expression[J]. J Nucl Med, 2004, 45(10): 1 776-1 783.
|
| [13] |
Chen X, Tohme M, Park R, et al. MicroPET imaging of alphavbeta3integrin expression with 18F-labeled dimeric RGD peptide[J]. Mol Imaging, 2004, 3(2): 96-104.
|
| [14] |
Li ZB, Cai W, Cao Q, et al. 64Cu-labeled tetrameric and octameric RGD peptides for smallanimal PET of tumor alpha(Ⅴ) beta(3) integrin expression[J]. J Nucl Med, 2007, 48(7): 1 162-1 171.
|
| [15] |
倪广惠,姜凤超. 整合素αⅤβ3拮抗剂的研究进展[J]. 药学学报, 2006, 41(7): 577-582.
|
| [16] |
Marinelli L, Lavecchia A, Gottschalk KE, et al. Docking studies on alphaⅤ beta3 integrin ligands: pharmacophore refinement and implications for drug design[J]. J Med Chem, 2003, 46(21): 4 393-4 404.
|
| [17] |
Moitessier N, Henry C, Maigret B, et al. Combining pharmacophore search, automated docking, and molecular dynamics simulations as a novel strategy for flexible docking. Proof of concept: docking of arginine-glycine-aspartic acid-like compounds into the alphaⅤ beta3 binding site[J]. J Med Chem, 2004, 47(17): 4 178-4 187.
|
| [18] |
Dayam R, Aiello F, Deng J, et al. Discovery of small molecule integrin alphavbeta3 antagonists as novel anticancer agents[J]. J Med Chem, 2006, 49(15): 4 526-4 534.
|
| [19] |
程刚英,倪广惠,姜凤超. 整合素αⅤβ3受体拮抗剂药效团模型的研究[J]. 药学学报, 2009, 44(4): 379-385.
|
| [20] |
Casiraghi G, Rassu G, Auzzas L, et al. Grafting aminocyclopentane carboxylic acids onto the RGD tripeptide sequence generates low nanomolar alphaⅤ beta3/alphaⅤ beta5 integrin dual binders[J]. J Med Chem, 2005, 48(24): 7 675-7 687.
|
| [21] |
Feuston BP, Culberson JC, Duggan ME, et al. Binding model for nonpeptide antagonists of alpha(Ⅴ)beta(3) integrin[J]. J Med Chem, 2002, 45(26): 5 640-5 648.
|
| [22] |
Raboisson P, Desjarlais RL, Reed R, et al. Identification of novel short chain 4-substituted indoles as potent alphaⅤ beta3 antagonist using structure-based drug design[J]. Eur J Med Chem, 2007, 42(3): 334-343.
|
| [23] |
纪庆,周圆,彭晖，等. 整合素αⅤβ3小分子抑制剂的设计及活性测定[J]. 中国医学科学院学报,2007,29(3): 347-352.
|
| [24] |
Zhou Y, Peng H, Ji Q, et al. Discovery of small molecule inhibitors of integrin αⅤβ3 through structurebased virtual screening[J]. Bioorg Med Chem Lett, 2006, 16: 5 878-5 882.
|
| [25] |
Chen X, Park R, Tohme M, et al. MicroPET and autoradiographic imaging of breast cancer αⅤ-integrin expression using 18F- and 64Cu-labeled RGD peptide[J]. Bioconjugate Chem, 2004, 15(1): 41-49.
|
| [26] |
Janssen ML, Oyen WJ, Dijkgraaf I, et al. Tumor targeting with radiolabeled alpha(Ⅴ)beta(3) integrin binding peptides in a nude mouse model[J]. Cancer Res, 2002, 62(21): 6 146-6 151.
|
| [27] |
Janssen M, Oyen WJ, Massuger LF, et al. Comparison of a monomeric and dimeric radiolabeled RGDpeptide for tumor targeting[J]. Cancer Biother Radiopharm, 2002, 17(6): 641-646.
|
| [28] |
Beer AJ, Haubner R, Goebel M, et al. Biodistribution and pharmacokinetics of the alphaⅤ beta3-selective tracer 18F-galacto-RGD in cancer patients[J]. J Nucl Med, 2005, 46(8): 1 333-1 341.
|
| [29] |
Schnell O, Krebs B, Carlsen J, et al. Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography[J]. Neuro Oncol, 2009, 11(6): 861-870.
|
| [30] |
Harris TD, Kalogeropoulos S, Nguyen T, et al. Design, synthesis, and evaluation of radiolabeled integrin alphaⅤ beta3 receptor antagonists for tumor imaging and radiotherapy[J]. Cancer Biother Radiopharm, 2003, 18(4): 627-641.
|
|
|
|
