Pharmacokinetics and tumor retention of 125I-labeled RGD peptide are improved by PEGylation
Pharmacokinetics and tumor retention of 125I-labeled RGD peptide are improved by PEGylation
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DOI：
10.1016/j.nucmedbio.2003.07.003
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Conti, PS
中科院分区：
文献类型：
--
作者：
Chen, XY;Park, R;Conti, PS
肿瘤生长和转移依赖于血管生成。整合素α(v)β(3)在血管生成血管以及多种人类恶性肿瘤中过度表达，这表明这种黏附受体的适当标记拮抗剂在肿瘤放射性核素成像和治疗方面具有潜力。包含精氨酸 - 甘氨酸 - 天冬氨酸（RGD）氨基酸序列的小的首尾相连的环肽已被放射性标记，并在临床前动物模型中进行了研究。然而，这种示踪剂血液清除快、肾脏和肝脏摄取高以及从肿瘤中快速洗脱，使其在临床应用中无效。在本研究中，我们用单官能甲氧基聚乙二醇（mPEG，分子量 = 2000）修饰环五肽c(RGDyK)，并用I - 125标记RGD - mPEG偶联物。我们通过对皮下移植U87MG胶质母细胞瘤的小鼠进行直接组织取样和放射自显影，研究了I - 125 - RGD - mPEG的肿瘤靶向效果和体内药代动力学特性。与I - 125 - RGD类似物相比，这种聚乙二醇化的RGD肽显示出血液清除更快、肾脏摄取更低以及肿瘤摄取时间延长，且不影响受体靶向能力。（C）2004爱思唯尔公司。保留所有权利。
Tumor growth and metastasis are angiogenesis dependent. Overexpression of integrin alpha(v)beta(3) in angiogenic vessels as well as various malignant human tumors suggests the potential of suitably labeled antagonists of this adhesion receptor for radionuclide imaging and therapy of tumors. Small head-to-tail cyclic peptides including the Arg-Gly-Asp (RGD) amino acid sequence have been radiolabeled and studied in preclinical animal models. However, the fast blood clearance, high kidney and liver uptake, and rapid washout from tumors make this type of tracer ineffective for clinical applications. In this study we modified the cyclic pentapeptide c(RGDyK) with monofunctional methoxy-PEG (mPEG, M.W. = 2,000) and labeled the RGD-mPEG conjugate with I-125. We studied the tumor targeting efficacy and in vivo pharmacokinetic properties of I-125-RGD-mPEG by means of direct tissue sampling and autoradiography in mice xenografted subcutaneously with U87MG glioblastoma. Compared to the I-125-RGD analog, this PEGylated RGD peptide revealed faster blood clearance, lower kidney uptake, and prolonged tumor uptake without compromising the receptor targeting ability. (C) 2004 Elsevier Inc. All rights reserved.