Preliminary Clinical Application of RGD-Containing Peptides as PET Radiotracers for Imaging Tumors

Abstract

Angiogenesis is a common feature of many physiological processes and pathological conditions. RGD-containing peptides can strongly bind to integrin αvβ3 expressed on endothelial cells in neovessels and several tumor cells with high specificity, making them promising molecular agents for imaging angiogenesis. Although studies of RGD-containing peptides combined with radionuclides, namely, 18F, 64Cu, and 68Ga for positron emission tomography (PET) imaging have shown high spatial resolution and accurate quantification of tracer uptake, only a few of these radiotracers have been successfully translated into clinical use. This review summarizes the RGD-based tracers in terms of accumulation in tumors and adjacent tissues, and comparison with traditional 18F-fluorodeoxyglucose (FDG) imaging. The value of RGD-based tracers for diagnosis, differential diagnosis, tumor subvolume delineation, and therapeutic response prediction is mainly discussed. Very low RGD accumulation, in contrast to high FDG metabolism, was found in normal brain tissue, indicating that RGD-based imaging provides an excellent tumor-to-background ratio for improved brain tumor imaging. However, the intensity of the RGD-based tracers is much higher than FDG in normal liver tissue, which could lead to underestimation of primary or metastatic lesions in liver. In multiple studies, RGD-based imaging successfully realized the diagnosis and differential diagnosis of solid tumors and also the prediction of chemoradiotherapy response, providing complementary rather than similar information relative to FDG imaging. Of most interest, baseline RGD uptake values can not only be used to predict the tumor efficacy of antiangiogenic therapy, but also to monitor the occurrence of adverse events in normal organs. This unique dual predictive value in antiangiogenic therapy may be better than that of FDG-based imaging.

Systematic Review: Targeted Molecular Imaging of Angiogenesis and Its Mediators in Rheumatoid Arthritis

“…The small size of the peptides allows them to be rapidly distributed and excreted from the body. Several promising variants of these RGD peptides with improved biodistribution and pharmacokinetics for α v β 3 integrin [79,84,207] are currently under clinical investigation for RA. Although α v β 3 is the main integrin used for imaging and targeting purposes, with relatively successful clinical application in the context of oncology and even in RA, there is still room for exploring other members of the integrin family.…”

Integrated MRI–Immune–Genomic Features Enclose a Risk Stratification Model in Patients Affected by Glioblastoma

“…These contentions, together with the limited clinical significance of Tumor Mutational Burden (TMB), have further tangled the road to define valid biomarkers in a GB setting. In this regard, actual interest has been shifted toward the intense immune-vascular interplay taking place in GB in reason of novel methodological approaches [61], and biologic discoveries on tumor immunity [62] and angiogenesis [63].…”

Identification of an IGF2BP2-Targeted Peptide for Near-Infrared Imaging of Esophageal Squamous Cell Carcinoma

“…Novel peptide-based molecular probes have facilitated cancer detection immensely, owing to the advent and rapid evolution of phage display technology [ 18 , 19 ]. Arg-Gly-Asp (RGD) peptide analogs, which target integrin α Ⅴ β 3 , have shown tremendous potential in the preliminary clinical exploration of the characterization of tumor angiogenesis [ 20 , 21 ] and have thus encouraged the exploration of a series of tumor-targeting peptides.…”