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

Li Li,Xiaoyuan Chen,Jinming Yu,Shuanghu Yuan

doi:10.3389/fonc.2022.837952

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.

Highlights

Angiogenesis, a well-known process by which new blood vessels sprout from the pre-existing capillaries, includes vascular endothelial cell activation, the degradation of vascular basement membrane during the activation, proliferation and migration of endothelial cells, and the construction of new blood vessels and vascular networks
The immature vessels are characterized by an undifferentiated endothelium and a lack of smooth muscles, and act as the vehicles for peripheral sprouting of new capillaries, invasion and distant metastasis [12–15]. These mechanisms are facilitated by the synergistic effects of transmission signals from the extracellular matrix (ECM) to endothelial cells, among which integrin binding to endothelial cell recognition sites is the first process to occur
For 18F-FPRGD2 uptake as a reflection of integrin avb3 staining on entire tumors, the mean SUVmax did not different between clear cell RCC (ccRCC) (4.1 ± 1.2) and papillary RCC (pRCC) (3.3 ± 0.7) [67]. These results indicated that integrin avb3 may highly expressed on tumor cells in ccRCC and new blood vessels in pRCC. 18F-FPRGD2 positron emission tomography (PET)/CT can reliably depict avb3 expression in renal tumors but is only representative of angiogenesis when tumor cells do not significantly express integrin avb3

Summary

Introduction

Angiogenesis, a well-known process by which new blood vessels sprout from the pre-existing capillaries, includes vascular endothelial cell activation, the degradation of vascular basement membrane during the activation, proliferation and migration of endothelial cells, and the construction of new blood vessels and vascular networks. In radioiodine refractoryIn differentiated thyroid cancer (RAIRDTC) patients, 18F-FDG PET/CT showed higher SUVmax compared to RGD PET/CT whether in primary tumor lesions or lymph node metastasis [91, 92]. These two tracers showed similar sensitivities of 82.3% in detecting lesions, but 68GaDOTA-RGD2 PET/CT had a higher specificity and accuracy of 100 and 86.4% compared to 50 and 75% for 18F-FDG PET/CT [92].

Results

Conclusion