Use of Radioiodinated Peptide Arg-Arg-Leu Targeted to Neovasculari- zation as well as Tumor Cells in Molecular Tumor Imaging.

Abstract

OBJECTIVE:

To explore a tumor peptide imaging agent Arginine-Arginine-Leucine (Tyr-Cys-Gly-Gly-Arg-Arg- Leu-Gly-Gly-Cys, tripeptide RRL [tRRL]) that targeted to tumor cells and tumor-derived endothelial cells (TDECs) and primarily investigate the possible relationship between tRRL and vascular endothelial growth factor receptor 2 (VEGFR-2).

METHODS:

The tRRL sequence motif was identified as a tumor molecular marker specifically binding to TDECs. Tyrosine was conjugated to the amino terminal of RRL (Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys) for labeling with radionuclide iodine-131 ((131)I-tRRL). The uptake ability and molecular binding of tRRL to tumor cells and angiogenic endothelium were studied using flow cytometry and radioactivity counter in vitro. Whether VEGFR-2 is the binging site of tRRL was investigated. Biodistribution and single-photon emission computed tomography (SPECT) imaging of (131)I-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice.

RESULTS:

In vitro cellular uptake experiments revealed that tRRL could not only adhere to tumor angiogenic endothelial cells but also largely accumulate in malignant tumor cells. VEGFR-2, which is highly expressed on TDECs, was probably not the solely binding ligand for tRRL targeted to tumor angiogenic endothelium. (131)I-tRRL mainly accumulated in tumors in vivo, not other organs at 24 h after injection. SPECT imaging with (131)I-tRRL clearly visualized tumors in nude mice, especially at 24 h.

CONCLUSION:

Radioiodinated tRRL offers a noninvasive nuclear imaging method for functional molecular imaging of tumors targeted to neovascularization, and may be a promising candidate for tumor radioimmunotherapeutic carrier.

• Authors: Xia Lu, Ping Yan, Rong-Fu Wang, Meng Liu, Ming-Ming Yu, Chun-Li Zhang
• Journal: Chinese journal of cancer research = Chung-kuo yen cheng yen chiu (Chin J Cancer Res) Vol. 24 Issue 1 Pg. 52-9 (Mar 2012) ISSN: 1000-9604 [Print] China
• PMID: 23359762 (Publication Type: Journal Article)