Peptides have an important role in organism and its high quantity present in tumors leading to development of radiolabeled peptides for tumor-specific imaging. Once the traditional methodologies used for radiofluorination do not work with peptides, due to their harsh conditions, other radiolabeling strategies had to be developed to supply the need. Direct radiofluorination is either an inefficient method, and the use of bidirectional groups, or prosthetic groups, is needed to enable the binding between the radionuclide fluorine-18 and a peptide functionalized. New peptides radiolabeling strategies have been developed sourcing increase the synthesis yield, its chemoselectivity, and the binding stability, and reduce the total process time and the number of steps required. The progress of radiofluorination methodologies led to development of the amidation, acylation, imidation, and alkylation techniques, the use of thiol groups, photochemical conjugation, chemoselective reactions, and “click chemistry”, in addition to use of FDG molecule and heteroatoms as linkers. This paper presents the main strategies used for peptides radiofluorination, presenting their positive and negative points, and the prosthetic groups most used in each method.
References
[1]
Ambrosini, V., Fani, M., Fanti, S., Forrer, F. and Maecke, H.R. (2011) Radiopeptide Imaging and Therapy in Europe. Journal of Nuclear Medicine, 52, 42S-55S. https://doi.org/10.2967/jnumed.110.085753
[2]
Jamous, M., Haberkorn, U. and Mier, W. (2013) Synthesis of Peptides Radiopharmaceuticals for the Therapy and Diagnosis of Tumor Diseases. Molecules, 18, 3379-3409. https://doi.org/10.3390/molecules18033379
[3]
Opalinska, M., Hubalewska-Dydejczyk, A. and Sowa-Staszczak, A. (2017) Radiolabeled Peptides: Current and New Perspectives. The Quarterly Journal of Nuclear Medicine and Molecular Imaging, 61, 153-167. https://doi.org/10.23736/S1824-4785.17.02971-5
[4]
Richter, S., Wuest, M., Bergman, C.N., Way, J.D., Krieger, S., Rogers, B.E. and Wuest, F. (2015) Rerouting the Metabolic Pathway of 18F-Labeled Peptides: The Influence of Prosthetic Groups. Bioconjugate Chemistry, 26, 201-212. https://doi.org/10.1021/bc500599m
[5]
Fani, M., Maecke, H.R. and Okarvi, S.M. (2012) Radiolabeled Peptides: Valuable Tools for the Detection and Treatment of Cancer. Theranostics, 2, 481-501. https://doi.org/10.7150/thno.4024
[6]
Knight, L.C. (2003) Chapter 23: Radiolabeled Peptides for Tumor Imaging. In: Welch, M.J. and Redvanly, C.S., Eds., Handbook of Radiopharmaceuticals: Radiochemistry and Applications, Wiley, Chichester, 643-684. https://doi.org/10.1002/0470846380.ch23
[7]
Wynendaele, E., Bracke, N., Stalmans, S. and Spiegeleer, B.D. (2014) Development of Peptide and Protein Based Radiopharmaceuticals. Current Pharmaceutical Design, 20, 2250-2267. https://doi.org/10.2174/13816128113196660663
[8]
Li, X., Cai, H., Wu, X., Li, L., Wu, H. and Tian, R. (2020) New Frontiers in Molecular Imaging Using Peptide-Based Radiopharmaceuticals for Prostate Cancer. Frontiers in Chemistry, 8, Article 583309. https://doi.org/10.3389/fchem.2020.583309
[9]
McBride, W.J., Sharkey, R.M., Karacay, H., D’Souza, C.A., Rossi, E.A., Laverman, P., Chang, C.-H., Boergman, O.C. and Goldenberg, D.M. (2009) A Novel Method of 18F Radiolabeling for PET. Journal of Nuclear Medicine, 50, 991-998. https://doi.org/10.2967/jnumed.108.060418
[10]
Van der Born, D., Pees, A., Poot, A.J., Orru, R.V.A., Windhorst, A.D. and Vugts, D.J. (2017) Fluorine-18 Labelled Building Blocks for PET Tracer Synthesis. Chemical Society Reviews, 46, 4709-4773. https://doi.org/10.1039/C6CS00492J
[11]
Wester, H.J. and Schottelius, M. (2007) Chapter 4: Fluorine-18 Labeling of Peptides and Proteins. In: Schubiger, P.A., Lehmann, L. and Friebe, M., Eds., PET Chemistry: The Driving Force in Molecular Imaging. Ernst Schering Research Foundation Workshop, Springer, Berlin, 79-111. https://doi.org/10.1007/978-3-540-49527-7_4
[12]
Wuest, F., Hultsch, C., Berndt, M. and Bergmann, R. (2009) Direct Labelling of Peptides with 2-[18F]Fluoro-2-Deoxy-D-Glucose ([18F]FDG). Bioorganic and Medicinal Chemistry Letters, 19, 5426-5428. https://doi.org/10.1016/j.bmcl.2009.07.108
[13]
Chin, J. (2013) Methods for Carbon-11 and Fluorine-18 Labeling of Peptides as PET Radiopharmaceuticals: Direct Labeling with [11C]Methyl Triflate on Cysteine Residues and [18F]Fluoride on the Cationic Silicon-Based Fluoride Acceptor (SIFA) Moiety. Department of Chemistry, McGill University, Montreal.
[14]
Marik, J. and Sutcliffe, J.L. (2006) Click for PET: Rapid Preparation of [18F]Fluoro-peptides Using CuI Catalyzed 1,3-Dipolar Cycloaddiation. Tetrahedron Letters, 47, 6681-6684. https://doi.org/10.1016/j.tetlet.2006.06.176
[15]
Guhlke, S., Coenen, H.H. and Stöcklin, G. (1994) Fluoroacylation Agents Based on Small N.C.A. [18F]Fluorocarboxylic Acids. Applied Radiation Isotopes, 45, 715-727. https://doi.org/10.1016/0969-8043(94)90252-6
[16]
Li, Z.-B., Wu, Z., Chen, K., Chin, F.T. and Chen, X. (2007) Click Chemistry for 18F-Labeling of RGD Peptides and Micropet Imaging of Tumor Integrin Αvβ3 Expression. Bioconjugate Chemistry, 18, 1987-1994. https://doi.org/10.1021/bc700226v
[17]
Wester, H.-J., Hamacher, K. and Stöcklin, G. (1996) A Comparative Study of N.C.A. Fluorine-18 Labeling of Proteins Via Acylation and Photochemical Conjugation. Nuclear Medicine and Biology, 23, 365-372. https://doi.org/10.1016/0969-8051(96)00017-0
[18]
Poethko, T., Schottelius, M., Thumshirn, G., Hersel, U., Herz, M., Henriksen, G., Kessler, H., Schwaiger, M. and Wester, H.-J. (2004) Two-Step Methodology for High-Yield Routine Radiohalohenation of Peptides: 18F-Labeled RGD and Octreotide Analogs. Journal of Nuclear Medicine, 45, 892-902.
[19]
Bruus-Jensen, K., Poethko, T., Schottelius, M., Hauser, A., Schwaiger, M. and Wester, H.-J. (2006) Chemoselective Hydrazone Formation between HYNIC-Functionalized Peptides and 18F-Fluorinated Aldehydes. Nuclear Medicine and Biology, 33, 173-183. https://doi.org/10.1016/j.nucmedbio.2005.10.010
[20]
Glaser, M. and Arstad, E. (2007) “Click Labeling” with 2-[18F]Fluoroethylazide for Positron Emission Tomography. Bioconjugate Chemistry, 18, 989-993. https://doi.org/10.1021/bc060301j
[21]
Gill, H.S. and Marik, J. (2011) Preparation of 18F-Labeled Peptides Using the Copper(I)-Catalyzed Azide-Alkyne 1,3-Dipolar Cycloaddition. Nature Protocols, 6, 1718-1725. https://doi.org/10.1038/nprot.2011.390
[22]
Ala, A., Walker, A.P., Ashkan, K., Dooley, J.S. and Schilsky, M.L. (2007) Wilson’s Disease. The Lancet, 369, 397-408. https://doi.org/10.1016/S0140-6736(07)60196-2
[23]
Brewer, G.J. (2010) Copper Toxicity in the General Population. Clinical Neurophysiology, 121, 459-460. https://doi.org/10.1016/j.clinph.2009.12.015
[24]
Maschauer, S. and Prante, O. (2014) Sweetening Pharmaceutical Radiochemistry by 18F-Fluoroglycosylation: A Short Review. Biomed Research International, 2014, Article ID: 214748. https://doi.org/10.1155/2014/214748
[25]
Albert, R., Marbach, P., Bauer, W., Briner, U., Fricker, G., Bruns, C. and Pless, J. (1993) SDZ CO 611: A Highly Potent Glycated Analog of Somatostatin with Improved Oral Activity. Life Science, 53, 517-525. https://doi.org/10.1016/0024-3205(93)90703-6
[26]
Haubner, R., Kuhnast, B., Mang, C., Weber, W.A., Kessler, H., Wester, H.-J. and Schwaiger, M. (2004) [18F]Galacto-RGD: Synthesis, Radiolabeling, Metabolic Stability, and Radiation Dose Estimates. Bioconjugate Chemistry, 15, 61-69. https://doi.org/10.1021/bc034170n
[27]
Kihlberg, J. and Ahman, J. (1995) Glycosylated Peptide Hormones: Pharmacological Properties and Conformational Studies of Analogues of [1-Desamino 8-D-Arginine] Vasopressin. Journal of Medical Chemistry, 38, 161-169. https://doi.org/10.1021/jm00001a021
[28]
Schottelius, M., Wester, H.-J., Reubi, J.C., Senekowitsch-Schmidtke, R. and Schwaigner, M. (2002) Improvement of Pharmacokinetics of Radioiodinated Tyr3-Octreotide by Conjugation with Carbohydrates. Bioconjugate Chemistry, 13, 1021-1030. https://doi.org/10.1021/bc0200069
[29]
Hultsch, C., Schottelius, M., Auernheimer, J., Alke, A. and Wester, H.-J. (2009) 18F-Fluoroglucosylation of Peptides, Exemplified on cyclo(RGDFK). European Journal of Nuclear Medicine and Molecular Imaging, 36, 1469-1474. https://doi.org/10.1007/s00259-009-1122-0
[30]
Namavari, M., Cheng, Z., Zhang, R., De, A., Levi, J., Hoerner, J.K., Yaghoubi, S.S., Syud, F.A. and Gambhir, S.S. (2009) A Novel Method for Direct Site-Specific Radiolabeling of Peptides Using [18F]FDG. Bioconjugate Chemistry, 20, 432-436. https://doi.org/10.1021/bc800422b
[31]
Price, N.P.J., Bowman, M.J., Gall, S.L., Berhow, M.A., Kendra, D.F. and Lerouge, P. (2010) Functionalized C-Glycoside Ketohydrazones: Carbohydrate Derivatives that Retain the Ring Integrity of the Terminal Reducing Sugar. Analytical Chemistry, 82, 2893-2899. https://doi.org/10.1021/ac902894u
[32]
Thapa, U. (2014) Fluoride-18 Labeling and Simultaneous Glycosylation of the Model Peptide Demobesin 1 by the Novel Prosthetic Group, Keto-[18F]FDG. Ph.M. Dissertation, Rheinischen Friedrich-Wilhelms-Universität Bonn, Bonn.
[33]
Allott, L., Pieve, C.D., Turton, D.R. and Smith, G. (2017) A General [18F]ALF Radiochemistry Procedure on Two Automated Synthesis Platforms. Reaction Chemistry and Engineering, 2, 68-74. https://doi.org/10.1039/C6RE00204H
[34]
Ting, R., Adam, M.J., Ruth, T.J. and Perrin, D.M. (2005) Arylfluoroborates and Alkylfluorosilicates as Potential PET Imaging Agents: High-Yielding Aqueous Biomolecular 18F-Labeling. Journal of the American Chemical Society, 127, 13094-13095. https://doi.org/10.1021/ja053293a
[35]
Harwig, C.W., Ting, R., Adam, M.J., Ruth, T.J. and Perrin, D.M. (2008) Synthesis and Characterization of 2,6-Difluoro-4-Carboxyphenylboronic Acid and a Biotin Derivative Thereof as Captors of Anionic Aqueous [18F]-Fluoride for the Preparation of [18F/19F]-Labeled Aryltrifluoroborates with High Kinetic Stability. Tetrahedron Letters, 49, 3152-3156. https://doi.org/10.1016/j.tetlet.2008.03.021
[36]
Ting, R., Lo, J., Adam, M.J., Ruth, T.J. and Perrin, D.M. (2008) Capturing Aqueous [18F]-Fluoride with an Arylboronic Ester for PET: Synthesis and Aqueous Stability of a Fluorescent [18F]-Labeled Aryltrifluoroborate. Journal of Fluorine Chemistry, 129, 349-358. https://doi.org/10.1016/j.jfluchem.2008.01.011
[37]
Ting, R., Harwig, C.W., Lo, J., Li, Y., Adam, M.J., Ruth, T.J. and Perrin, D.M. (2008) Substituent Effects on Aryltrifluoroborate Solvolysis in Water: Implications for Suzuki-Miyaura Coupling and the Design of Stable 18F-Labeled Aryltrifluoroborates for Use in PET Imaging. Journal of Organic Chemistry, 73, 4662-4670. https://doi.org/10.1021/jo800681d
[38]
Elizarov, A.M., Van Dam, R.M., Shin, Y.S., Kolb, H.C., Padgett, H.C., Stout, D., Shu, J., Huang, J., Daridon, A. and Heath, J.R. (2010) Design and Optimization of Coin-Shaped Microreactor Chips for PET Radiopharmaceutical Synthesis. Journal of Nuclear Medicine, 51, 282-287. https://doi.org/10.2967/jnumed.109.065946
[39]
Liu, Z., Li, Y., Lozada, J., Pan, J., Lin, K.-S., Schaffer, P. and Perrin, D.M. (2012) Rapid, One-Step, High Yielding 18F-Labeling of an Aryltrifluoroborate Bioconjugate by Isotope Exchange at Very High Specific Activity. Labelled Compounds and Radiopharmaceuticals, 55, 491-496. https://doi.org/10.1002/jlcr.2990
[40]
Liu, Z., Li, Y., Lozada, J., Schaffer, P., Adam, M.J., Ruth, T.J. and Perrin, D.M. (2013) Stoichiometric Leverage: Rapid 18F-Aryltrifluoroborate Radiosynthesis at High Specific Activity for Click Conjugation. Angewandte Chemie International Edition, 52, 2303-2307. https://doi.org/10.1002/anie.201208551
[41]
Mu, L., Höhne, A., Schubiger, P.A., Ametamey, S.M., Graham, K., Cyr, J.E., Dinkelborg, L., Stellfeld, T., Srinivasan, A., Voigtmann, U. and Klar, U. (2008) Silicon-Based Building Blocks for One-Step 18F-Radiolabeling of Peptides for PET Imaging. Angewandte Chemie International Edition, 47, 4922-4925. https://doi.org/10.1002/anie.200705854
[42]
Höhne, A., Mu, L., Honer, M., Schubiger, P.A., Ametamey, S.M., Graham, K., Stellfeld, T., Borkowski, S., Berndorff, D., Klar, U., Voigtmann, U., Cyr, J.E., Friebe, M., Dinkelborg, L. and Srinivasan, A. (2008) Synthesis, 18F-Labeling, and in Vitro and in Vivo Studies of Bombesin Peptides Modified with Silicon-Based Building Blocks. Bioconjugate Chemistry, 19, 1871-1879. https://doi.org/10.1021/bc800157h
[43]
Höhne, A., Yu, L., Mu, L., Reiher, M., Voigtmann, U., Klar, U., Graham, K., Schubiger, P.A. and Ametamey, S.M. (2009) Organofluorosilanes as Model Compounds for 18F-Labeled Silicon-Based PET Tracers and Their Hydrolytic Stability: Experimental Data and Theoretical Calculations. Chemistry—A European Journal, 15, 3736-3743. https://doi.org/10.1002/chem.200802437
[44]
Laverman, P., McBride, W.J., Sharkey, R.M., Eek, A., Joosten, L., Oyen, W.J.G., Goldenberg, D.M. and Boerman, O.C. (2010) A Novel Facile Method of Labeling Octreotide with 18F-Fluorine. Journal of Nuclear Medicine, 51, 454-461. https://doi.org/10.2967/jnumed.109.066902
[45]
Iovkova, L., Wängler, B., Schirrmacher, E., Schirrmacher, R., Quandt, G., Boening, G., Schürmann, M. and Jurkschat, K. (2009) Para-Functionalized Aryl-di-tert-butylfluorosilanes as Potential Labeling Synthons for 18F Radiopharmaceuticals. Chemistry—A European Journal, 15, 2140-2147. https://doi.org/10.1002/chem.200802266
[46]
Schirrmacher, R., Bradtmöller, G., Schirrmacher, E., Thewsm, O., Tillmanns, J., Siessmeier, T., Buchholz, H.G., Bartenstein, P., Wängler, B., Neimeyer, C.M. and Jurkschat, K. (2006) 18F-Labeling of Peptides by Means of an Organosilicon-Based Fluoride Acceptor. Angewandte Chemie International Edition, 45, 6047-6050. https://doi.org/10.1002/anie.200600795
[47]
Schirrmacher, E., Wängler, B., Cypryk, M., Bradtmöller, G., Schäfer, M., Eisenhut, K.J. and Schirrmacher, R. (2007) Synthesis of P-(Di-Tert-Butyl[18F]Fluorosilyl) Benzaldehyde ([18F]SIFA-A) with High Specific Activity by Isotopic Exchange: A Convenient Labeling Synthon for the 18F-Labeling of N-Amino-Oxy Derivatized Peptides. Bioconjugate Chemistry, 18, 2085-2089. https://doi.org/10.1021/bc700195y
[48]
Kostikov, A.P., Chin, J., Orchowski, K., Niedermoses, S., Kovacevic, M.M., Aliaga, A., Jurkschat, K., Wängler, B., Wängler, C., Wester, H.-J. and Schirrmacher, R. (2012) Oxalic Acid Supported Si-18F-Radiofluorination: One-Step Radiosynthesis of N-Succinimidyl 3-(Di-tert-butyl[18F]fluorosilyl)benzoate ([18F]SIFB) for Protein Labeling. Bioconjugate Chemistry, 23, 106-114. https://doi.org/10.1021/bc200525x
[49]
Wängler, B., Quandt, G., Iovkova, L., Schirrmacher, E., Wängler, C., Boening, G., Hacker, M., Schmoeckel, M., Jurkschat, K., Bartenstein, P. and Schirrmacher, R. (2009) Kit-Like 18F-Labeling of Proteins: Synthesis of 4-(Di-tert-butyl[18F]fluorosilyl)benzenethiol (Si[18F]FA-SH) Labeled Rat Serum Albumin for Blood Pool Imaging with PET. Bioconjugate Chemistry, 20, 317-321. https://doi.org/10.1021/bc800413g
[50]
Archibald, S.J. and Allott, L. (2021) The Aluminium-[18F]Fluoride Revolution: Simple Radiochemistry with a Big Impact for Radiolabelled Biomolecules. EJNMMI Radiopharmacy and Chemistry, 6, Article No. 30. https://doi.org/10.1186/s41181-021-00141-0
