nach oben

Erschienen in:

15.08.2018 | Research Article

Site-Specific Labeling of F-18 Proteins Using a Supplemented Cell-Free Protein Synthesis System and O-2-[¹⁸F]Fluoroethyl-L-Tyrosine: [¹⁸F]FET-HER2 Affibody Molecule

verfasst von: Ai Yanai, Ryuichi Harada, Ren Iwata, Takeo Yoshikawa, Yoichi Ishikawa, Shozo Furumoto, Takanori Ishida, Kazuhiko Yanai

Erschienen in: Molecular Imaging and Biology | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Although a preparation method for F-18-labeled proteins that used a cell-free translation system and 4-[¹⁸F]fluoro-L-proline instead of L-proline has been reported, its introduction depends on amino acid sequences of target proteins. The purpose of the study was to propose site-specific labeling method of F-18 by using cell-free translation systems supplemented with an engineered orthogonal aminoacyl-tRNA synthetase derived from Methanocaldococcus jannaschii (pCNF-RS)/suppressor tRNA (tRNA_CUA^opt) pair, O-2-[¹⁸F]fluoroethyl-L-tyrosine ([¹⁸F]FET), and template DNA inserted with an amber codon.

Procedures

[¹⁸F]FET was prepared from the corresponding precursor and determined whether [¹⁸F]FET could be incorporated into an affibody molecule for human epidermal growth factor receptor type 2 (HER2; Z_HER2:342) as the 21st amino acid used with the pCNF-RS-tRNA_CUA^opt pair and template DNA inserted with an amber codon in a cell-free translation system. Using SKOV-3 cells, we performed an in vitro binding assay of [¹⁸F]FET-Z_HER2:342. Furthermore, in vivo positron emission tomography (PET) imaging in SKOV-3 xenograft-bearing mice was performed after the intravenous administration of [¹⁸F]FET-Z_HER2:342.

Results

[¹⁸F]FET was successfully incorporated into proteins by using commercially available cell-free protein synthesis reagents with a pCNF-RS-tRNA_CUA^opt pair and template DNA of the desired proteins inserted with an amber codon. The mean radiochemical yield (non-decay-corrected) of [¹⁸F]FET-Z_HER2:342 was 6.5 ± 4.1 %. An in vitro cell binding assay revealed that SKOV-3 cells–bound [¹⁸F]FET-Z_HER2:342 expressed HER2. The in vivo PET imaging in SKOV-3 xenograft-bearing mice revealed that [¹⁸F]FET-Z_HER2:342 accumulated in SKOV-3 xenografts.

Conclusion

The method proposed in this study might be useful for preparing proteins with F-18 and molecular imaging in the preclinical development.

Nur mit Berechtigung zugänglich

Koerber JT, Thomsen ND, Hannigan BT, Degrado WF, Wells JA (2013) Nature-inspired design of motif-specific antibody scaffolds. Nat Biotechnol 31:916–921CrossRefPubMedPubMedCentral

Colombo I, Overchuk M, Chen J, Reilly RM, Zheng G, Lheureux S (2017) Molecular imaging in drug development: update and challenges for radiolabeled antibodies and nanotechnology. Methods 130:23–35CrossRefPubMed

Moek KL, Giesen D, Kok IC, de Groot DJA, Jalving M, Fehrmann RSN, Lub-de Hooge MN, Brouwers AH, de Vries EGE (2017) Theranostics using antibodies and antibody-related therapeutics. J Nucl Med 58:83S–90SCrossRef

Tolmachev V, Orlova A, Nilsson FY, Feldwisch J, Wennborg A, Abrahmsén L (2007) Affibody molecules: potential for in vivo imaging of molecular targets for cancer therapy. Expert Opin Biol Ther 7:555–568CrossRefPubMed

Orlova A, Magnusson M, Eriksson TL et al (2006) Tumor imaging using a picomolar affinity HER2 binding affibody molecule. Cancer Res 66:4339–4348CrossRefPubMed

Wallberg H, Grafstrom J, Cheng Q, Lu L, Martinsson Ahlzen HS, Samen E, Thorell JO, Johansson K, Dunas F, Olofsson MH, Stone-Elander S, Arner ESJ, Stahl S (2012) HER2-positive tumors imaged within 1 hour using a site-specifically ¹¹C-labeled Sel-tagged affibody molecule. J Nucl Med 53:1446–1453CrossRefPubMed

Glaser M, Iveson P, Hoppmann S, Indrevoll B, Wilson A, Arukwe J, Danikas A, Bhalla R, Hiscock D (2013) Three methods for ¹⁸F labeling of the HER2-binding affibody molecule Z_HER2:2891 including preclinical assessment. J Nucl Med 54:1981–1988CrossRefPubMed

Harada R, Furumoto S, Yoshikawa T, Ishikawa Y, Shibuya K, Okamura N, Ishiwata K, Iwata R, Yanai K (2016) Synthesis and characterization of ¹⁸F-interleukin-8 using a cell-free translation system and 4-¹⁸F-fluoro-L-proline. J Nucl Med 57:634–639CrossRefPubMed

Harada R, Furumoto S, Yoshikawa T, Ishikawa Y, Shibuya K, Okamura N, Iwata R, Yanai K (2012) Synthesis of [¹¹C]interleukin 8 using a cell-free translation system and L-[¹¹C]methionine. Nucl Med Biol 39:155–160CrossRefPubMed

10.

Shimizu Y, Inoue A, Tomari Y, Suzuki T, Yokogawa T, Nishikawa K, Ueda T (2001) Cell-free translation reconstituted with purified components. Nat Biotechnol 19:751–755CrossRefPubMed

11.

Liu CC, Schultz PG (2010) Adding new chemistries to the genetic code. Annu Rev Biochem 79:413–444CrossRefPubMed

12.

Wang L, Brock A, Herberich B, Schultz PG (2001) Expanding the genetic code of Escherichia coli. Science 292:498–500CrossRefPubMed

13.

Goerke AR, Swartz JR (2008) Development of cell-free protein synthesis platforms for disulfide bonded proteins. Biotechnol Bioeng 99:351–367CrossRefPubMed

14.

Ozawa K, Loscha KV, Kuppan KV, Loh CT, Dixon NE, Otting G (2012) High-yield cell-free protein synthesis for site-specific incorporation of unnatural amino acids at two sites. Biochem Biophys Res Commun 418:652–656CrossRefPubMed

15.

Young DD, Young TS, Jahnz M, Ahmad I, Spraggon G, Schultz PG (2011) An evolved aminoacyl-tRNA synthetase with atypical polysubstrate specificity. Biochemistry 50:1894–1900CrossRefPubMedPubMedCentral

16.

Tolmachev V, Hofstrom C, Malmberg J et al (2010) HEHEHE-tagged affibody molecule may be purified by IMAC, is conveniently labeled with [^99mTc(CO₃)]⁺, and shows improved biodistribution with reduced hepatic radioactivity accumulation. Bioconjug Chem 21:2013–2022CrossRefPubMed

17.

Young TS, Ahmad I, Yin JA, Schultz PG (2010) An enhanced system for unnatural amino acid mutagenesis in E. coli. J Mol Biol 395:361–374CrossRefPubMed

18.

Iwata R, Pascali C, Terasaki K, Ishikawa Y, Furumoto S, Yanai K (2018) Practical microscale one-pot radiosynthesis of (18) F-labeled probes. J Labelled Comp Radiopharm 61:540–549CrossRefPubMed

19.

Hamacher K, Coenen HH (2002) Efficient routine production of the ¹⁸F-labelled amino acid O-2-¹⁸F fluoroethyl-L-tyrosine. Appl Radiat Isot 57:853–856CrossRefPubMed

20.

Loening AM, Gambhir SS (2003) AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2:131–137CrossRefPubMed

21.

Qi Y, Liu X, Li J, Yao H, Yuan S (2017) Fluorine-18 labeled amino acids for tumor PET/CT imaging. Oncotarget 8:60581–60588PubMedPubMedCentral

22.

Rapp M, Heinzel A, Galldiks N, Stoffels G, Felsberg J, Ewelt C, Sabel M, Steiger HJ, Reifenberger G, Beez T, Coenen HH, Floeth FW, Langen KJ (2013) Diagnostic performance of ¹⁸F-FET PET in newly diagnosed cerebral lesions suggestive of glioma. J Nucl Med 54:229–235CrossRefPubMed

23.

Dunet V, Rossier C, Buck A, Stupp R, Prior JO (2012) Performance of ¹⁸F-fluoro-ethyl-tyrosine (¹⁸F-FET) PET for the differential diagnosis of primary brain tumor: a systematic review and Metaanalysis. J Nucl Med 53:207–214CrossRefPubMed

24.

Kramer-Marek G, Kiesewetter DO, Martiniova L, Jagoda E, Lee SB, Capala J (2008) [¹⁸F]FBEM-Z(HER2:342)-affibody molecule-a new molecular tracer for in vivo monitoring of HER2 expression by positron emission tomography. Eur J Nucl Med Mol Imaging 35:1008–1018CrossRefPubMed

25.

Morris O, Fairclough M, Grigg J, et al. (2018) A review of approaches to (18) F radiolabelling affinity peptides and proteins. J Labelled Comp Radiopharm

26.

Eigenbrot C, Ultsch M, Dubnovitsky A, Abrahmsen L, Hard T (2010) Structural basis for high-affinity HER2 receptor binding by an engineered protein. Proc Natl Acad Sci U S A 107:15039–15044CrossRefPubMedPubMedCentral

27.

Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, Stöcklin G (1999) Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J Nucl Med 40:205–212PubMed

28.

Stahl S, Graslund T, Eriksson Karlstrom A et al (2017) Affibody molecules in biotechnological and medical applications. Trends Biotechnol 35:691–712CrossRefPubMed

29.

Ahlgren S, Orlova A, Wallberg H, Hansson M, Sandstrom M, Lewsley R, Wennborg A, Abrahmsen L, Tolmachev V, Feldwisch J (2010) Targeting of HER2-expressing tumors using ¹¹¹In-ABY-025, a second-generation affibody molecule with a fundamentally reengineered scaffold. J Nucl Med 51:1131–1138CrossRefPubMed

30.

Orlova A, Tolmachev V, Pehrson R, Lindborg M, Tran T, Sandstrom M, Nilsson FY, Wennborg A, Abrahmsen L, Feldwisch J (2007) Synthetic affibody molecules: a novel class of affinity ligands for molecular imaging of HER2-expressing malignant tumors. Cancer Res 67:2178–2186CrossRefPubMed

Titel: Site-Specific Labeling of F-18 Proteins Using a Supplemented Cell-Free Protein Synthesis System and O-2-[18F]Fluoroethyl-L-Tyrosine: [18F]FET-HER2 Affibody Molecule
verfasst von: Ai Yanai
Ryuichi Harada
Ren Iwata
Takeo Yoshikawa
Yoichi Ishikawa
Shozo Furumoto
Takanori Ishida
Kazuhiko Yanai
Publikationsdatum: 15.08.2018
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 3/2019
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1266-z

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Site-Specific Labeling of F-18 Proteins Using a Supplemented Cell-Free Protein Synthesis System and O-2-[¹⁸F]Fluoroethyl-L-Tyrosine: [¹⁸F]FET-HER2 Affibody Molecule