Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Research Article

A Uniquely Modified DKL-based Peptide Probe for Positron Emission Tomography Imaging

Author(s): Yi Liu, Zhengjie Wang, Xiang Li, Fei Kang, Xiaowei Ma, Weidong Yang, Wenhui Ma* and Jing Wang*

Volume 25, Issue 1, 2019

Page: [96 - 103] Pages: 8

DOI: 10.2174/1381612825666190329151326

Price: $65

Abstract

Peptides containing the asparagine-glycine-arginine (NGR) motif can target the tumor neovascular biomarker CD13/aminopeptidase N receptor. D-K6L9 is a tumor-selective anti-cancer peptide. To improve the capacity of NGR peptides to target tumors, we joined the NGR and D-K6L9 peptides to form NKL. Next, we linked 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to NKL and labeled it with gallium 68 (68Ga, t1/2 = 67.7 min) to form 68Ga-DOTA-NKL. This novel probe was characterized in vitro. 68Ga-DOTA-NKL was stable in phosphate buffered saline at room temperature and in human serum at 37°C. We determined that the uptake rate of 68Ga-DOTA-NKL in CD13 receptor-positive 22Rv1 tumor cells was 3.15% ± 0.04 after 2 h, and tested 68Ga-DOTA-NKL using positron emission tomography (PET)/computed tomography imaging in vivo. MicroPET imaging results revealed that 22Rv1 tumor uptake of 68Ga-DOTA-NKL was 8.69 ± 0.20, 6.61 ± 0.22, 3.85 ± 0.06, and 1.41 ± 0.23 percentage injected dose per gram of tissue (%ID/g) at 0.5, 1, 2, and 3 h postinjection (pi), respectively. The tumor-to-background contrast in the subcutaneous human prostate cancer 22Rv1 mouse model was 9.97 ± 1.90. The 68Ga-DOTA-NKL probe has combined tumor-targeting and tumor-selective properties, and may be used to diagnose CD13-positive tumors.

Keywords: Anticancer peptide, CD13 receptor, NGR peptide, PET/CT imaging, tumor targeting, Tomography.

[1]
Sun X, Cai W, Chen X. Positron emission tomography imaging using radiolabeled inorganic nanomaterials. Accounts Chem Res 2015; 48: 286-94.
[2]
Opacic T, Paefgen V, Lammers T, Kiessling F. Status and trends in the development of clinical diagnostic agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2017; 9.
[3]
Ma W, Li G, Wang J, et al. In vivo NIRF imaging-guided delivery of a novel NGR-VEGI fusion protein for targeting tumor vasculature. Amino Acids 2014; 46: 2721-32.
[4]
Koivunen E, Wang B, Ruoslahti E. Isolation of a highly specific ligand for the α5β1 integrin from a phage display library. J Cell Biol 1994; 124: 373-80.
[5]
Li G, Wang X, Zong S, Wang J, Conti PS, Chen K. MicroPET imaging of CD13 expression using 64Cu-labeled dimeric NGR peptide based on sarcophagine cage. Mol Pharm 2014; 11: 3938-46.
[6]
Ma W, Wang Z, Yang W, Ma X, Kang F, Wang J. Biodistribution and SPECT imaging study of 99mTc labeling NGR peptide in nude mice bearing human HepG2 hepatoma. BioMed Res Int 2014; 2014: 1-6.
[7]
Ma W, Kang F, Wang Z, et al. 99mTc-labeled monomeric and dimeric NGR peptides for SPECT imaging of CD13 receptor in tumor-bearing mice. Amino Acids 2013; 44: 1337-45.
[8]
Hu J, Chen C, Zhang S, et al. Designed antimicrobial and antitumor peptides with high selectivity. Biomacromolecules 2011; 12: 3839-43.
[9]
Chen C, Chen Y, Yang C, et al. High selective performance of designed antibacterial and anticancer peptide amphiphiles. Acs Appl Mater Inter 2015; 7: 17346-55.
[10]
Li G, Xing Y, Wang J, Conti PS, Chen K. Near-infrared fluorescence imaging of CD13 receptor expression using a novel Cy5.5-labeled dimeric NGR peptide. Amino Acids 2014; 46: 1547-56.
[11]
Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002; 415: 389-95.
[12]
Hancock REW, Chapple DS. Peptide antibiotics. Antimicrob Agents Chemother 1999; 43: 1317-23.
[13]
Papo N, Shahar M, Eisenbach L, Shai Y. A novel lytic peptide composed of D, L amino acids selectively kills cancer cells in culture and in mice. J Biol Chem 2003; 278: 21018-23.
[14]
Cichoń T, Smolarczyk R, Matuszczak S, Barczyk M, Jarosz M, Szala S. D-K6L9 peptide combination with IL-12 inhibits the recurrence of tumors in mice. Arch Immunol Ther Ex 2014; 62: 341-51.
[15]
Papo N, Seger D, Makovitzki A, et al. Inhibition of tumor growth and elimination of multiple metastases in human prostate and breast xenografts by systemic inoculation of a host defense-like lytic peptide. Cancer Res 2006; 66: 5371-8.
[16]
Ito K, Teng R, Schöder H, et al. F-18 FDG PET/CT for monitoring of ipilimumab therapy in patients with metastatic melanoma. J Nucl Med 2018; 118: 213652.
[17]
Francis R, Segard T, Morandeau L. Novel molecular imaging in lung and pleural diseases. Respirology 2011; 16: 1173-88.
[18]
Weininger U, Liu Z, McIntyre DD, Vogel HJ, Akke M. Specific 12CβD212CγD2 S13CεHD2 isotopomer labeling of methionine to characterize protein dynamics by 1H and 13C NMR relaxation dispersion. J Am Chem Soc 2012; 134: 18562-5.
[19]
Costello DA, Millet JK, Hsia C, Whittaker GR, Daniel S. Single particle assay of coronavirus membrane fusion with proteinaceous receptor-embedded supported bilayers. Biomaterials 2013; 34: 7895-904.
[20]
Shao Y, Liang W, Kang F, et al. 68Ga-labeled cyclic NGR peptide for microPET imaging of CD13 receptor expression. Molecules 2014; 19: 11600-12.
[21]
Manabe O, Ohira H, Hirata K, et al. Use of 18F-FDG PET/CT texture analysis to diagnose cardiac sarcoidosis. Eur J Nucl Med Mol Imaging 2018.
[http://dx.doi.org/10.1007/soo259-018-4195-9]
[22]
Liu Z, Ehlerding EB, Cai W, Lan X. One-step synthesis of an 18F-labeled boron-derived methionine analog: A substitute for 11C-methionine? Eur J Nucl Med Mol I 2018; 45: 582-4.
[23]
Uprimny C, Svirydenka A, Fritz J, et al. Comparison of [68Ga]Ga-PSMA-11 PET/CT with [18F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy. Eur J Nucl Med Mol Imaging 2018; 45: 1873-83.
[24]
Molinaa MA, Goodwinb WJ, Moffata FL, Serafinic AN, Sfakianakisc GN, Avisar E. Intra-operative use of PET probe for localization of FDG avid lesions. Cancer Imaging 2009; 9: 59-62.
[25]
Le CP, Nowell CJ, Kim-Fuchs C, et al. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat Commun 2016; 7: 10634.
[26]
Seidi K, Jahanban-Esfahlan R, Monhemi H, et al. NGR (Asn-Gly-Arg)-targeted delivery of coagulase to tumor vasculature arrests cancer cell growth. Oncogene 2018; 37: 3967-80.
[27]
Papo N, Braunstein A, Eshhar Z, Shai Y. Suppression of human prostate tumor growth in mice by a cytolytic D-, L-amino acid peptide. Cancer Res 2004; 64: 5779-86.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy