MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide
MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide
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DOI：
10.1007/s00259-003-1452-2
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发表时间：
2004-08-01
影响因子：
9.1
通讯作者：
Conti, PS
中科院分区：
文献类型：
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作者：
Chen, XY;Park, R;Conti, PS
我们之前已经通过人工4-[F-18]氟苯甲酰基部分用氟-18标记环状RGD多肽c(RGDyK)，并将这种[F-18]FB-RGD放射性示踪剂应用于不同临床前肿瘤模型的α(V)-整合素表达成像，具有良好的肿瘤与背景对比度。然而，该示踪剂的肝胆排泄不良，肿瘤洗脱速度快，限制了其潜在的临床应用。本研究的目的是通过在F-18放射性标记和RGD部分之间插入一个异双功能聚乙二醇来修饰[F-18]FB-RGD示踪剂，并测试这种[F-18]FB-PEG-RGD示踪剂的脑肿瘤靶向性和体内动力学。在弱碱性条件下(pH=8.5)，将RGD-聚乙二醇偶联物与N-琥珀酰亚胺4-[F-18]氟苯甲酸酯([F-18]SFB)偶联，制备了[F-18]FB-PEG-RGD。以活化酯[F-18]SFB计，放化产率约为20-30%，比活度大于100GBq/mumol。在皮下U87 MG胶质母细胞瘤模型中，该示踪剂具有快速的血液清除、快速的肿瘤摄取和较高的摄取能力(给药30min时为5.2+/-0.5%ID/g)。肿瘤洗脱速度较快，4h后活性积聚降至2.2+/-0.4%ID/g。MicroPET和放射自显影成像显示，肿瘤与背景的比率非常高，肝脏、肾脏和肠道中的活动积聚有限。[F-18]FB-PEG-RGD对移植于小鼠前脑的U87 MG肿瘤具有良好的显示效果。尽管原位肿瘤的摄取明显低于原位肿瘤(P
We have previously labeled cyclic RGD peptide c(RGDyK) with fluorine-18 through conjugation labeling via a prosthetic 4-[F-18]fluorobenzoyl moiety and applied this [F-18]FB-RGD radiotracer for alpha(v)-integrin expression imaging in different preclinical tumor models with good tumor-to-background contrast. However, the unfavorable hepatobiliary excretion and rapid tumor washout rate of this tracer limit its potential clinical applications. The aims of this study were to modify the [F-18]FB-RGD tracer by inserting a heterobifunctional poly(ethylene glycol) (PEG, M.W. = 3,400) between the F-18 radiolabel and the RGD moiety and to test this [F-18]FB-PEG-RGD tracer for brain tumor targeting and in vivo kinetics. [F-18]FB-PEG-RGD was prepared by coupling the RGD-PEG conjugate with N-succinimidyl 4-[F-18]fluorobenzoate ([F-18]SFB) under slightly basic conditions (pH=8.5). The radiochemical yield was about 20-30% based on the active ester [F-18]SFB, and specific activity was over 100 GBq/mumol. This tracer had fast blood clearance, rapid and high tumor uptake in the subcutaneous U87MG glioblastoma model (5.2 +/- 0.5%ID/g at 30 min p.i.). Moderately rapid tumor washout was observed, with the activity accumulation decreased to 2.2 +/- 0.4%ID/g at 4 h p.i. MicroPET and autoradiography imaging showed a very high tumor-to-background ratio and limited activity accumulation in the liver, kidneys and intestinal tracts. U87MG tumor implanted into the mouse forebrain was well visualized with [F-18]FB-PEG-RGD. Although uptake in the orthotopic tumor was significantly lower (P