Direct incorporation of [18F] into Aliphatic Systems: A promising Mn-catalysed Labelling Technique for PET Imaging

Author(s): Sara Cesarec, Jonathan A. Robson, Laurence S. Carroll*, Eric O. Aboagye, Alan C. Spivey

Journal Name: Current Radiopharmaceuticals

Volume 14 , Issue 2 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: One of the challenges in positron emission tomography (PET) is labelling complex aliphatic molecules.

Objective: This study aimed to develop a method of metal-catalysed radiofluorination that is site-selective and works in moderate to good yields under facile conditions.

Methods: Herein, we report on the optimisation of an aliphatic C-H to C-18F bond transformation catalysed by a Mn(porphyrin) complex.

Results: The successful oxidation of 11 aliphatic molecules, including progesterone, is reported. Radiochemical Incorporations (RCIs) up to 69% were achieved within 60 min without the need for pre-activation or special equipment.

Conclusion: The method features mild conditions (60 °C) and promises to constitute a valuable approach to labelling of biomolecules and drug substances.

Keywords: PET, [18F]-Fluoride, aliphatic labelling, imaging, mn-Catalysed, porphyrin, tracer synthesis, nucleophilic fluorination.

[1]
Kubota, K. From tumor biology to clinical Pet: a review of positron emission tomography (PET) in oncology. Ann. Nucl. Med., 2001, 15(6), 471-486.
[http://dx.doi.org/10.1007/BF02988499] [PMID: 11831394]
[2]
Hargreaves, R.J. The role of molecular imaging in drug discovery and development. Clin. Pharmacol. Ther., 2008, 83(2), 349-353.
[http://dx.doi.org/10.1038/sj.clpt.6100467] [PMID: 18167503]
[3]
Donnelly, D.J. Small Molecule PET Tracers in Drug Discovery. Semin. Nucl. Med., 2017, 47(5), 454-460.https://doi.org/https://doi.org/10.1053/j.semnuclmed.2017.05.006
[http://dx.doi.org/10.1053/j.semnuclmed.2017.05.006] [PMID: 28826520]
[4]
Kelkar, S.S.; Reineke, T.M. Theranostics: combining imaging and therapy. Bioconjug. Chem., 2011, 22(10), 1879-1903.
[http://dx.doi.org/10.1021/bc200151q] [PMID: 21830812]
[5]
Ametamey, S.M.; Honer, M.; Schubiger, P.A. Molecular imaging with PET. Chem. Rev., 2008, 108(5), 1501-1516.
[http://dx.doi.org/10.1021/cr0782426] [PMID: 18426240]
[6]
Preshlock, S.; Tredwell, M.; Gouverneur, V. (18)F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography. Chem. Rev., 2016, 116(2), 719-766.
[http://dx.doi.org/10.1021/acs.chemrev.5b00493] [PMID: 26751274]
[7]
Wang, J.; Sánchez-Roselló, M.; Aceña, J.L.; del Pozo, C.; Sorochinsky, A.E.; Fustero, S.; Soloshonok, V.A.; Liu, H. Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011). Chem. Rev., 2014, 114(4), 2432-2506.
[http://dx.doi.org/10.1021/cr4002879] [PMID: 24299176]
[8]
Gillis, E.P.; Eastman, K.J.; Hill, M.D.; Donnelly, D.J.; Meanwell, N.A. Applications of Fluorine in Medicinal Chemistry. J. Med. Chem., 2015, 58(21), 8315-8359.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00258] [PMID: 26200936]
[9]
d’Amico, A. Review of clinical practice utility of positron emission tomography with 18F-fluorodeoxyglucose in assessing tumour response to therapy. Radiol. Med. (Torino), 2015, 120(4), 345-351.
[http://dx.doi.org/10.1007/s11547-014-0446-4] [PMID: 25155349]
[10]
Vingerhoets, F.J.G.; Schulzer, M.; Ruth, T.J.; Holden, J.E.; Snow, B.J. Reproducibility and discriminating ability of fluorine-18-6-fluoro-L-Dopa PET in Parkinson’s disease. J. Nucl. Med., 1996, 37(3), 421-426.
[PMID: 8772636]
[11]
Jacobson, O.; Kiesewetter, D.O.; Chen, X. Fluorine-18 radiochemistry, labeling strategies and synthetic routes. Bioconjug. Chem., 2015, 26(1), 1-18.
[http://dx.doi.org/10.1021/bc500475e] [PMID: 25473848]
[12]
Mossine, A.V.; Brooks, A.F.; Ichiishi, N.; Makaravage, K.J.; Sanford, M.S.; Scott, P.J.H. Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination. Sci. Rep., 2017, 7(1), 233.
[http://dx.doi.org/10.1038/s41598-017-00110-1] [PMID: 28331174]
[13]
Brooks, A.F.; Topczewski, J.J.; Ichiishi, N.; Sanford, M.S.; Scott, P.J.H. Late-stage [18F]Fluorination: New Solutions to Old Problems. Chem. Sci. (Camb.), 2014, 5(12), 4545-4553.
[http://dx.doi.org/10.1039/C4SC02099E] [PMID: 25379166]
[14]
Sanford, M.S.; Scott, P.J.H. Moving Metal-Mediated (18)F-Fluorination from Concept to Clinic. ACS Cent. Sci., 2016, 2(3), 128-130.
[http://dx.doi.org/10.1021/acscentsci.6b00061] [PMID: 27163039]
[15]
Lee, E.; Kamlet, A. S.; Powers, D. C.; Neumann, C. N.; Boursalian, G. B.; Furuya, T.; Choi, D. C.; Hooker, J. M.; Ritter, T. A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging. Science (80-. )., 2011, 334, 639-642.
[http://dx.doi.org/10.1126/science.1212625]
[16]
Kamlet, A.S.; Neumann, C.N.; Lee, E.; Carlin, S.M.; Moseley, C.K.; Stephenson, N.; Hooker, J.M.; Ritter, T. Application of palladium-mediated (18)F-fluorination to PET radiotracer development: overcoming hurdles to translation. PLoS One, 2013, 8(3)e59187
[http://dx.doi.org/10.1371/journal.pone.0059187] [PMID: 23554994]
[17]
Lee, E.; Hooker, J.M.; Ritter, T. Nickel-mediated oxidative fluorination for PET with aqueous [18F] fluoride. J. Am. Chem. Soc., 2012, 134(42), 17456-17458.
[http://dx.doi.org/10.1021/ja3084797] [PMID: 23061667]
[18]
Ren, H.; Wey, H-Y.; Strebl, M.; Neelamegam, R.; Ritter, T.; Hooker, J.M. Synthesis and imaging validation of [¹⁸F]MDL100907 enabled by Ni-mediated fluorination. ACS Chem. Neurosci., 2014, 5(7), 611-615.
[http://dx.doi.org/10.1021/cn500078e] [PMID: 24845956]
[19]
Hoover, A.J.; Lazari, M.; Ren, H.; Narayanam, M.K.; Murphy, J.M.; van Dam, R.M.; Hooker, J.M.; Ritter, T. A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil from [18F]Fluoride for Human PET Imaging. Organometallics, 2016, 35(7), 1008-1014.
[http://dx.doi.org/10.1021/acs.organomet.6b00059] [PMID: 27087736]
[20]
Ichiishi, N.; Brooks, A.F.; Topczewski, J.J.; Rodnick, M.E.; Sanford, M.S.; Scott, P.J.H. Copper-catalyzed [18F]fluorination of (mesityl)(aryl)iodonium salts. Org. Lett., 2014, 16(12), 3224-3227.
[http://dx.doi.org/10.1021/ol501243g] [PMID: 24890658]
[21]
McCammant, M.S.; Thompson, S.; Brooks, A.F.; Krska, S.W.; Scott, P.J.H.; Sanford, M.S. Cu-Mediated C-H 18F-Fluorination of Electron-Rich (Hetero)arenes. Org. Lett., 2017, 19(14), 3939-3942.
[http://dx.doi.org/10.1021/acs.orglett.7b01902] [PMID: 28665619]
[22]
Mossine, A.V.; Brooks, A.F.; Makaravage, K.J.; Miller, J.M.; Ichiishi, N.; Sanford, M.S.; Scott, P.J.H. Synthesis of [18F]Arenes via the Copper-Mediated [18F]Fluorination of Boronic Acids. Org. Lett., 2015, 17(23), 5780-5783. [18F].
[http://dx.doi.org/10.1021/acs.orglett.5b02875] [PMID: 26568457]
[23]
Tredwell, M.; Preshlock, S.M.; Taylor, N.J.; Gruber, S.; Huiban, M.; Passchier, J.; Mercier, J.; Génicot, C.; Gouverneur, V. A general copper-mediated nucleophilic 18F fluorination of arenes. Angew. Chem. Int. Ed. Engl., 2014, 53(30), 7751-7755.
[http://dx.doi.org/10.1002/anie.201404436] [PMID: 24916101]
[24]
aGraham, T.J.A.; Lambert, R.F.; Ploessl, K.; Kung, H.F.; Doyle, A.G. Enantioselective radiosynthesis of positron emission tomography (PET) tracers containing [¹⁸F]fluorohydrins. J. Am. Chem. Soc., 2014, 136(14), 5291-5294. [18F].
[http://dx.doi.org/10.1021/ja5025645] [PMID: 24628021]
bWebb, E.W.; Park, J.B.; Cole, E.L.; Donnelly, D.J.; Bonacorsi, S.J.; Ewing, W.R.; Doyle, A.G. Nucleophilic (Radio)Fluorination of Redox-Active Esters via Radical-Polar Crossover Enabled by Photoredox Catalysis. J. Am. Chem. Soc., 2020, 142(20), 9493-9500.
[http://dx.doi.org/10.1021/jacs.0c03125] [PMID: 32378889]
[25]
Buckingham, F.; Kirjavainen, A.K.; Forsback, S.; Krzyczmonik, A.; Keller, T.; Newington, I.M.; Glaser, M.; Luthra, S.K.; Solin, O.; Gouverneur, V. Organomediated Enantioselective (18)F Fluorination for PET Applications. Angew. Chem. Int. Ed. Engl., 2015, 54(45), 13366-13369.
[http://dx.doi.org/10.1002/anie.201506035] [PMID: 26360631]
[26]
Buckingham, F.; Gouverneur, V. Asymmetric 18F-fluorination for applications in positron emission tomography. Chem. Sci. (Camb.), 2016, 7(3), 1645-1652.
[http://dx.doi.org/10.1039/C5SC04229A] [PMID: 28808536]
[27]
Nodwell, M.B.; Yang, H.; Čolović, M.; Yuan, Z.; Merkens, H.; Martin, R.E.; Bénard, F.; Schaffer, P.; Britton, R. 18F-Fluorination of Unactivated C-H Bonds in Branched Aliphatic Amino Acids: Direct Synthesis of Oncological Positron Emission Tomography Imaging Agents. J. Am. Chem. Soc., 2017, 139(10), 3595-3598.
[http://dx.doi.org/10.1021/jacs.6b11533] [PMID: 28248493]
[28]
Huang, X.; Liu, W.; Ren, H.; Neelamegam, R.; Hooker, J.M.; Groves, J.T. Late stage benzylic C-H fluorination with [¹⁸F]fluoride for PET imaging. J. Am. Chem. Soc., 2014, 136(19), 6842-6845.
[http://dx.doi.org/10.1021/ja5039819] [PMID: 24766544]
[29]
Liu, W.; Groves, J.T. Manganese Catalyzed C-H Halogenation. Acc. Chem. Res., 2015, 48(6), 1727-1735.
[http://dx.doi.org/10.1021/acs.accounts.5b00062] [PMID: 26042637]
[30]
Liu, W.; Huang, X.; Placzek, M.S.; Krska, S.W.; McQuade, P.; Hooker, J.M.; Groves, J.T. Site-Selective 18F Fluorination of Unactivated C-H Bonds Mediated by a Manganese Porphyrin. Chem. Sci. (Camb.), 2018, 9, 1168-1172.
[http://dx.doi.org/10.1039/C7SC04545J] [PMID: 29675161]
[31]
Carroll, L.; Evans, H.L.; Spivey, A.C.; Aboagye, E.O. Mn-salen catalysed benzylic C-H activation for the synthesis of aryl [(18)F]CF3-containing PET probes. Chem. Commun. (Camb.), 2015, 51(40), 8439-8441.
[http://dx.doi.org/10.1039/C4CC05762G] [PMID: 25714781]
[32]
Bume, D.D.; Harry, S.A.; Lectka, T.; Pitts, C.R. Catalyzed and Promoted Aliphatic Fluorination. J. Org. Chem., 2018, 83(16), 8803-8814.
[http://dx.doi.org/10.1021/acs.joc.8b00982] [PMID: 29894188]
[33]
Groves, J.T.; Stern, M.K. Synthesis, Characterization, and Reactivity of Oxomanganese(IV). Porphyrin Complexes. J. Am. Chem. Soc., 1988, 110(26), 8628-8638.
[http://dx.doi.org/10.1021/ja00234a009]
[34]
Geraskin, I.M.; Pavlova, O.; Neu, H.M.; Yusubov, M.S.; Nemykin, V.N.; Zhdankin, V.V. Comparative Reactivity of Hypervalent Iodine Oxidants in Metalloporphyrin-Catalyzed Oxygenation of Hydrocarbons: Iodosylbenzene Sulfate and 2-Iodylbenzoic Acid Ester as Safe and Convenient Alternatives to Iodosylbenzene. Adv. Synth. Catal., 2009, 351(5), 733-737.
[http://dx.doi.org/10.1002/adsc.200800784]
[35]
Nassar, E.; El-Farargy, A.F.; Abdelrazek, F.M. Synthesis of Some Novel Cyclooctane-Fused-Heterocycles with Anticipated Biological Activities. J. Heterocycl. Chem., 2015, 52(5), 1395-1399.
[http://dx.doi.org/10.1002/jhet.2246]
[36]
Larson, S.M.; Morris, M.; Gunther, I.; Beattie, B.; Humm, J.L.; Akhurst, T.A.; Finn, R.D.; Erdi, Y.; Pentlow, K.; Dyke, J.; Squire, O.; Bornmann, W.; McCarthy, T.; Welch, M.; Scher, H. Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. J. Nucl. Med., 2004, 45(3), 366-373.
[PMID: 15001675]
[37]
Lazari, M.; Lyashchenko, S.K.; Burnazi, E.M.; Lewis, J.S.; van Dam, R.M.; Murphy, J.M. Fully-automated synthesis of 16β-(18)F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer. Appl. Radiat. Isot., 2015, 103(Suppl. C), 9-14.https://doi.org/https://doi.org/10.1016/j.apradiso.2015.05.010
[http://dx.doi.org/10.1016/j.apradiso.2015.05.010] [PMID: 26046518]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 14
ISSUE: 2
Year: 2021
Published on: 07 September, 2020
Page: [101 - 106]
Pages: 6
DOI: 10.2174/1874471013666200907115026
Price: $65

Article Metrics

PDF: 47
HTML: 1