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http://dx.doi.org/10.22643/JRMP.2019.5.2.83

Facile radiolabeling of antibody-mimetic protein with In-111 via an inverse-electron-demand Diels-Alder reaction  

Nam, You Ree (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Shim, Ha Eun (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Lee, Dong-Eun (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Publication Information
Journal of Radiopharmaceuticals and Molecular Probes / v.5, no.2, 2019 , pp. 83-88 More about this Journal
Abstract
In order to understand the in vivo biodistribution of repebody protein (RB), an efficient and simple radiolabeling method for the protein is needed. We demonstrate a detailed protocol for the radiosynthesis of an 111In radiolabeled tetrazine prosthetic group and its application to the efficient radiolabeling of trans-cyclooctene-group conjugated repebody protein using inverse-electron-demand Diels-Alder reaction. First, 1,2,4,5-tetrazine (Tz) conjugated with a DOTA chelator, was used for preparing the radiolabeled DOTA complex with 111In. Second, the trans-cyclooctene (TCO) functionalized repebody protein was synthesized which allows for the preparation of radiolabeled proteins by copper-free click chemistry. Following incubation with the 111In-radiolabeled DOTA complex (111In-Tz), the TCO-functionalized RB (TCO-RB) was radiolabeled successfully with 111In, with a high radiochemical yield (69.5%) and radiochemical purity (>99%). The radiolabeling of repebody protein by copper-free click chemistry was accomplished within 20 min, with great efficiency in aqueous conditions. These results clearly indicate that the present radiolabeling method will be useful for the efficient and convenient radiolabeling of trans-cyclooctene-group containing biomolecules.
Keywords
Radiolabeling; In-111; invers-electron-demand Diels-Alder reaction; repebody protein; radio-ITLC;
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1 Kishimoto T. Interleukin-6: from basic science to medicine--40 years in immunology. Annu Rev Immunol 2005;23:1-21.   DOI
2 Hong DS, Angelo LS, Kurzrock R. Interleukin-6 and its receptor in cancer: implications for translational therapeutics. Cancer 2007;110:1911-1928.   DOI
3 Nagasaki T, Hara M, Shiga K, Takeyama H. Relationship between inflammation and cancer progression: review of the recent advances in interleukin-6 signaling and its blockage in cancer therapy. Receptors Clin Investig 2014;1:e202.
4 Chames P, Regenmortel MV, Weiss E, Baty D. Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 2009;157:220-233.   DOI
5 Skrlec K, Strukelj B, Berlec A. Non-immunoglobulin scaffolds: a focus on their targets. Trends Biotechnol 2015;33:408-418.   DOI
6 Gronwall C, Stahl S. Engineered affinity proteins-generation and applications. J Biotechnol 2009;140:254-269.   DOI
7 Skerra A. Alternative non-antibody scaffolds for molecular recognition. Curr Opin Biotechnol 2007;18:295-304.   DOI
8 Binz HK, Amstutz P, Pluckthun A. Engineering novel binding proteins from nonimmunoglobulin domains. Nat Biotechnol 2005;23:1257-1268.   DOI
9 Simeon R, Chen Z. In vitro-engineered non-antibody protein therapeutics. Protein Cell 2017;9:3-14.   DOI
10 Nuttall SD, Walsh RB. Display scaffolds: protein engineering for novel therapeutics. Curr Opin Pharmacol 2008;8:609-615.   DOI
11 Nygren PA, Skerra A. Binding proteins from alternative scaffolds. J Immunol Methods 2004;290:3-28.   DOI
12 Banta S, Dooley K, Shur O. Replacing antibodies: engineering new binding proteins. Annu Rev Biomed Eng 2013;15:93-113.   DOI
13 Hey T, Fiedler E, Rudolph R, Fiedler M. Artificial, non-antibody binding proteins for pharmaceutical and industrial applications. Trends Biotechnol 2005;23:514-522.   DOI
14 Kim TY, Seo HD, Lee JJ, Kang JA, Kim WS, Kim HM, Song HY, Park JM, Lee DE, Kim HS. A dimeric form of a small-sized protein binder exhibits enhanced anti-tumor activity through prolonged blood circulation. J Control Release 2018;279:282-291.   DOI
15 Tolmachev V, Orlova A. Influence of labelling methods on biodistribution and imaging properties of radiolabelled peptides for visualisation of molecular therapeutic targets. Curr Med Chem 2010;17:2636-2655.   DOI
16 Lee JJ, Kim HJ, Yang CS, Kyeong HH, Choi JM, Hwang DE, Yuk JM, Park K, Kim YJ, Lee SG, Kim D, Jo EK, Cheong HK, Kim HS. A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer. Mol Ther 2014;22:1254-1265.   DOI
17 Hwang DE, Ryou JH, Oh JR, Han JW, Park TK, Kim HS. Anti-human VEGF repebody effectively suppresses choroidal neovascularization and vascular leakage. PLoS One 2016;11:e0152522.   DOI
18 Hwang DE, Choi JM, Yang CS, Lee JJ, Heu W, Jo EK, Kim HS. Effective suppression of C5a-induced proinflammatory response using anti-human C5a repebody. Biochem Biophys Res Commun 2016;477:1072-1077.   DOI
19 Mushtaq S, Rho JK, Kang JA, Lee JJ, Kim JY, Nam YR, Yun SJ, Lee GH, Park SH, Lee DE, Kim HS. Radiolabeling and preliminary biodistribution study of 99mTc-labeled antibody-mimetic scaffold protein repebody for initial clearance properties. Bioorg Med Chem Lett 2017;27:5060-5064.   DOI
20 Zahnd C, Kawe M, Stumpp MT, de Pasquale C, Tamaskovic R, Nagy-Davidescu G, Dreier B, Schibli R, Binz HK, Waibel R, Pluckthun A. Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: effects of affinity and molecular size. Cancer Res 2010;70:1595-1605.   DOI
21 Keinanen, O, Li X, Chenna NK, Lumen D, Ott J, Molthoff CFM, Sarparanta M, Helariutta K, Vuorinen T, Windhorst AD, Airaksinen AJ. A new highly reactive and low lipophilicity fluorine-18 labeled tetrazine derivative for pretargeted PET Imaging. ACS Med Chem Lett 2016;7:62-66.   DOI
22 Choi JY, Lee BC. Click reaction: an applicable radiolabeling method for molecular imaging. Nucl Med Mol Imaging 2015;49:258-267.   DOI
23 Rossin R, van den Bosch SM, ten Hoeve W, Carvelli M, Versteegen RM, Lub J, Robillard MS. Highly Reactive trans-cyclooctene tags with improved stability for Diels-Alder chemistry in living systems. Bioconjugate Chem 2013;24:1210-1217.   DOI
24 Zeglis BM, Sevak KK, Reiner T, Mohindra P, Carlin SD, Zanzonico P, Weissleder R, Lewis JS. A pretargeted PET imaging strategy based on bioorthogonal Diels-Alder click chemistry. J Nucl Med 2013;54:1389-1396.   DOI
25 Selvaraj R, Fox JM. trans-Cyclooctene - a stable, voracious dienophile for bioorthogonal labeling. Curr Opin Chem Biol 2013;17:753-760.   DOI
26 Herth MM, Andersen VL, Lehel S, Madsen J, Knudsen GM, Kristensen JL. Development of a $^{11}C$-labeled tetrazine for rapid tetrazine-trans-cyclooctene ligation. Chem Commun 2013;49:3805-3807.   DOI
27 Li Z, Cai H, Hassink M, Blackman ML, Brown RC, Conti PS, Fox JM. Tetrazine-trans-cyclooctene ligation for the rapid construction of $^{18}F$ labeled probes. Chem Commun 2010;46:8043-8045.   DOI
28 van Onzen AHAM, Rossin R, Schenning APHJ, Nicolay K, Milroy LG, Robillard MS, Brunsveld L. Tetrazinetrans-cyclooctene chemistry applied to fabricate selfassembled fluorescent and radioactive nanoparticles for in vivo dual mode imaging. Bioconjugate Chem 2019;30:547-551.   DOI
29 Rossin R, Verkerk PR, van den Bosch SM, Vulders RC, Verel I, Lub J, Robillard MS. In vivo chemistry for pretargeted tumor imaging in live mice. Angew Chem Int Ed 2010;49:3375-3378.   DOI
30 Rossin R, Lappchen T, van den Bosch SM, Laforest R, Robillard MS. Diels-Alder reaction for tumor pretargeting: In vivo chemistry can boost tumor radiation dose compared with directly antibody. J Nucl Med 2013;54:1989-1995.   DOI
31 Kim TY, Park JH, Shim HE, Choi DS, Lee DE, Song JJ, Kim HS. Prolonged half-life of small-sized therapeutic protein using serum albumin specific protein binder. J Control Release 2019;315:31-39.   DOI