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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.08.2004 | Original Article

MicroPET imaging of brain tumor angiogenesis with ¹⁸F-labeled PEGylated RGD peptide

verfasst von: Xiaoyuan Chen, Ryan Park, Yingping Hou, Vazgen Khankaldyyan, Ignacio Gonzales-Gomez, Michel Tohme, James R. Bading, Walter E. Laug, Peter S. Conti

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 8/2004

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Abstract

We have previously labeled cyclic RGD peptide c(RGDyK) with fluorine-18 through conjugation labeling via a prosthetic 4-[¹⁸F]fluorobenzoyl moiety and applied this [¹⁸F]FB-RGD radiotracer for α_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 [¹⁸F]FB-RGD tracer by inserting a heterobifunctional poly(ethylene glycol) (PEG, M.W. =3,400) between the ¹⁸F radiolabel and the RGD moiety and to test this [¹⁸F]FB-PEG-RGD tracer for brain tumor targeting and in vivo kinetics. [¹⁸F]FB-PEG-RGD was prepared by coupling the RGD-PEG conjugate with N-succinimidyl 4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) under slightly basic conditions (pH=8.5). The radiochemical yield was about 20–30% based on the active ester [¹⁸F]SFB, and specific activity was over 100 GBq/μmol. 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 [¹⁸F]FB-PEG-RGD. Although uptake in the orthotopic tumor was significantly lower (P<0.01) than in the subcutaneous tumor, the maximum tumor-to-brain ratio still reached 5.0±0.6 due to low normal brain background. The results of H&E staining post mortem agreed with the anatomical information obtained from non-invasive microPET imaging. In conclusion, PEGylation suitably modifies the physiological behavior of the RGD peptide. [¹⁸F]FB-PEG-RGD gave improved tumor retention and in vivo kinetics compared with [¹⁸F]FB-RGD.

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Titel: MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide
verfasst von: Xiaoyuan Chen
Ryan Park
Yingping Hou
Vazgen Khankaldyyan
Ignacio Gonzales-Gomez
Michel Tohme
James R. Bading
Walter E. Laug
Peter S. Conti
Publikationsdatum: 01.08.2004
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 8/2004
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-003-1452-2

Springer Medizin

Abstract

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