18F-FP-PEG2-β-Glu-RGD2: A Symmetric Integrin αvβ3-Targeting Radiotracer for Tumor PET Imaging

Abstract

Radiolabeled cyclic arginine-glycine-aspartic (RGD) peptides can be used for noninvasive determination of integrin αvβ3 expression in tumors. In this study, we performed radiosynthesis and biological evaluation of a new 18F-labeled RGD homodimeric peptide with one 8-amino-3,6-dioxaoctanoic acid (PEG2) linker on the glutamate β-amino group (18F-FP-PEG2-β-Glu-RGD2) as a symmetric PET tracer for tumor imaging. Biodistribution studies showed that radioactivity of 18F-FP-PEG2-β-Glu-RGD2 was rapidly cleared from blood by predominately renal excretion. MicroPET-CT imaging with 18F-FP-PEG2-β-Glu-RGD2 revealed high tumor contrast and low background in A549 human lung adenocarcinoma-bearing mouse models, PC-3 prostate cancer-bearing mouse models, and orthotopic transplanted C6 brain glioma models. 18F-FP-PEG2-β-Glu-RGD2 exhibited good stability in vitro and in vivo. The results suggest that this tracer is a potential PET tracer for tumor imaging.

Synthesis and comparative in vivo evaluation of 99mTc(CO)3‐labeled PEGylated and non‐PEGylated cRGDfK peptide monomers

“…Small PEG units (PEG 2 , PEG 3 , PEG 4 ) incorporated in RGD peptides are reported to improve the pharmacokinetics, whereas long-chain PEG (MW = 3400) due to increase in molecular size lead to spatial hindrance thus reducing the affinity toward the receptors as well as clearance. [26][27][28] In the present study, medium-sized PEG 7 linker was introduced with an aim of increasing the biological half-life of the peptide that may lead to increase in the tumor uptake of the radiotracer.…”

“…PEGylation of peptides is a common method to manipulate the pharmacokinetics . Effect of shorter PEGs, PEG 2 , PEG 3 , and PEG 4 as well as longer PEG (MW = 3400) on the in vivo kinetics of radiolabeled RGD peptides has been reported in the literature. In this study, we incorporated a medium PEG with seven repeating units of ethylene glycol (___O___CH 2 ___CH 2 ___) 7 at ε‐amino group of lysine of cRGDfK peptide.…”

Molecular imaging of integrins in oncology

“…42 During the last 2 years, some modifications in the molecular architecture of the RGDbased tracers have been described. One evaluated compound 43 This study shows that minor structural modifications can easily be applied to successful compounds, yielding similar imaging results but no improvement or progress in the field.…”

PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin αvβ3 Receptors

“…The effects of a symmetric beta-Glu linker in combination with a PEG 2 (3-(2-(2-aminoethoxy)ethoxy)propanoic acid) connecting the β -glutamate’s amino group with the radiolabeling domain were studied with the 18 F-labeled c(RGD) homodimeric peptide [ 18 F]FP-PEG 2 - β -E[c(RGDyK)] 2 17 ( Figure 5 ) [ 47 ]. The protruding free PEG-amino group of the symmetric β -glutamate linker in PEG 2 - β -E[c(RGDyK)] 2 encountered less steric hindrance for the installation of [ 18 F]FP compared to the asymmetric PEG- α -E[c(RGDyK)] 2 , resulting in a higher-yielding radiolabeling preparation of [ 18 F]FP-PEG 2 - β- E[c(RGDyK)] 2 17 (c.a.…”