Novel small peptides derived from VEGF125-136: potential drugs for radioactive diagnosis and therapy in A549 tumor-bearing nude mice

Abstract

Vascular endothelial growth factor receptor (VEGFR) is a critical factor in tumor angiogenesis and has been considered a potential target for receptor-mediated radionuclide imaging and therapy. In this study, we identified two peptides (QKRKRKKSRKKH and RKRKRKKSRYIVLS) derived from VEGF125-136 that displayed high binding affinities to VEGFR and strong inhibition of A549 cell growth. 99mTc- and 188Re-labeled peptides displayed high labeling efficiency and favorable stability in saline and human plasma. At the cellular level, the radiolabeled peptides could bind with A549 cells and be internalized via the VEGFR-1-mediated pathway. 99mTc/188Re-labeled peptide was significantly accumulated at xenograft tumors, as observed with single-photon emission computed tomography (SPECT) planar imaging. Moreover, 188Re-labeled peptides significantly inhibited tumor growth, prolonged the survival time of the tumor-bearing nude mice and resulted in much more necrotic regions and apoptotic cells in the A549 xenograft tumors. These results demonstrated that these two peptides as candidate drugs for radionuclide imaging and tumor therapy.

Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives

“…A number of peptides have been radiolabeled with 188 Re, mainly somatostatin derivatives (164–168). Other considered targets include gastrin releasing peptide receptor (GRPr) with bombesin (169) or GRPr-antagonist RM26 (170), α V β 3 integrin (169), NK1 receptors, with Substance P (171), HCC with SP94 peptide (172), VEGFR (173) or GRP78, a specific cancer cell-surface marker (174). Much work has also been done on targeting melanoma, either through melanin or melanocortin-1 receptor (MC1-R) (162, 175, 176).…”

PET Imaging of VEGFR with a Novel 64Cu-Labeled Peptide

“…Besides, several research efforts have been put toward affibody and peptide-based radiotracers. 35,36 These molecules showed satisfactory PK and image contrast, but their imaging mode is based on SPECT, which significantly limits signal sensitivity and image quality. Compared to SPECT, PET exhibits several advantages, including improved image quality, greater interpretive certainty, higher diagnostic accuracy, and lower patient dosimetry.…”

“…Several molecular imaging agents have been applied to detect and quantify VEGFR in angiogenic tumors, such as radiotracers for use in single-photon emission computed tomography (SPECT) and positron emission tomography (PET). − For example, Chen et al developed PET radiotracers based on VEGF-A isoforms for imaging VEGFR. , More recently, several VEGFR-2-specific monoclonal antibodies labeled with copper-64 or zirconium-89 have shown encouraging results for the selective imaging of VEGFR-2. , Despite these advances, mAb-based imaging agents have shown unfavorable pharmacokinetics (PK) and high nonspecific uptake. Besides, several research efforts have been put toward affibody and peptide-based radiotracers. , These molecules showed satisfactory PK and image contrast, but their imaging mode is based on SPECT, which significantly limits signal sensitivity and image quality. Compared to SPECT, PET exhibits several advantages, including improved image quality, greater interpretive certainty, higher diagnostic accuracy, and lower patient dosimetry .…”