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Peptides as Radiopharmaceutical Vectors

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Radiopharmaceutical Chemistry

Abstract

Over the last decade, there has been a significant and rapidly growing interest in the use of radiolabeled receptor-binding peptides for both nuclear imaging and targeted radiotherapy. This is underscored by the recent FDA approval of NETSPOT, a peptide labeled with gallium-68 for the PET imaging of neuroendocrine tumors. As small protein fragments, peptides are attractive radiopharmaceuticals for several reasons, notably their ease of synthesis, tolerance of structural modifications for radiolabeling, high affinity and selectivity for receptors, rapid pharmacokinetics, and lack of immunogenicity. A notable drawback for some peptides, however, lies in their low metabolic stability. This chapter describes the overall process for the development of radiolabeled peptides, including their design, radiosynthesis, optimization, and in vitro and in vivo evaluation. In addition, it highlights some of the most exciting recent and future clinical applications of these radiopharmaceuticals.

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References

  1. Kaspar AA, Reichert JM. Future directions for peptide therapeutics development. Drug Discov Today. 2013;18(17–18):807–17.

    CAS  PubMed  Google Scholar 

  2. Okarvi SM, Maecke HR. Radiolabelled peptides in medical imaging. In: Koutsopoulos S, editor. Peptide applications in biomedicine, biotechnology and bioengineering. Duxford: Woodhead Publishing; 2018. p. 431–83.

    Google Scholar 

  3. Chatalic KLS, Kwekkeboom DJ, de Jong M. Radiopeptides for imaging and therapy: a radiant future. J Nucl Med. 2015;56(12):1809–12.

    CAS  PubMed  Google Scholar 

  4. Fosgerau K, Hoffmann T. Peptide therapeutics: current status and future directions. Drug Discov Today. 2015;20(1):122–8.

    CAS  PubMed  Google Scholar 

  5. Wetzler M, Hamilton P. Peptides as therapeutics. In: Koutsopoulos S, editor. Peptide applications in biomedicine, biotechnology and bioengineering. Duxford: Woodhead Publishing; 2018. p. 215–30.

    Google Scholar 

  6. Correia JD, Paulo A, Raposinho PD, Santos I. Radiometallated peptides for molecular imaging and targeted therapy. Dalton Trans. 2011;40(23):6144–67.

    CAS  PubMed  Google Scholar 

  7. Demoin DW, Wyatt LC, Edwards KJ, Abdel-Atti D, Sarparanta M, Pourat J, et al. PET imaging of extracellular pH in tumors with 64Cu- and 18F-labeled pHLIP peptides: a structure–activity optimization study. Bioconjug Chem. 2016;27(9):2014–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. van Duijnhoven SMJ, Robillard MS, Nicolay K, Grull H. Tumor targeting of MMP-2/9 activatable cell-penetrating imaging probes is caused by tumor-independent activation. J Nucl Med. 2011;52(2):279–86.

    PubMed  Google Scholar 

  9. Dufresne M, Seva C, Fourmy D. Cholecystokinin and gastrin receptors. Physiol Rev. 2006;86(3):805–47.

    CAS  PubMed  Google Scholar 

  10. Maschauer S, Einsiedel J, Hübner H, Gmeiner P, Prante O. 18F- and 68Ga-Labeled neurotensin peptides for PET imaging of neurotensin receptor 1. J Med Chem. 2016;59(13):6480–92.

    CAS  PubMed  Google Scholar 

  11. Haubner R, Maschauer S, Prante O. PET radiopharmaceuticals for imaging integrin expression: Tracers in clinical studies and recent developments. Biomed Res Int. 2014;2014:1–17.

    Google Scholar 

  12. Okarvi SM. Peptide-based radiopharmaceuticals: future tools for diagnostic imaging of cancers and other diseases. Med Res Rev. 2004;24(3):357–97.

    CAS  PubMed  Google Scholar 

  13. Levine R, Krenning EP. Clinical history of the theranostic radionuclide approach to neuroendocrine tumors and other types of cancer: historical review based on an interview of Eric P. Krenning by Rachel Levine. J Nucl Med. 2017;58(Suppl. 2):3S–9S.

    CAS  PubMed  Google Scholar 

  14. Barrio M, Czernin J, Fanti S, Ambrosini V, Binse I, Du L, et al. The Impact of somatostatin receptor–directed PET/CT on the management of patients with neuroendocrine tumor: a systematic review and meta-analysis. J Nucl Med. 2017;58(5):756–61.

    PubMed  Google Scholar 

  15. Jadvar H, Chen X, Cai W, Mahmood U. Radiotheranostics in cancer diagnosis and management. Radiology. 2018;286(2):388–400.

    PubMed  PubMed Central  Google Scholar 

  16. Morgat C, Mishra AK, Varshney R, Allard M, Fernandez P, Hindie E. Targeting neuropeptide receptors for cancer imaging and therapy: perspectives with bombesin, neurotensin, and neuropeptide-Y receptors. J Nucl Med. 2014;55(10):1650–7.

    CAS  PubMed  Google Scholar 

  17. Sah BR, Burger IA, Schibli R, Friebe M, Dinkelborg L, Graham K, et al. Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer. J Nucl Med. 2015;56(3):372–8.

    CAS  PubMed  Google Scholar 

  18. Yu Z, Ananias HJK, Carlucci G, Hoving HD, Helfrich W, Dierckx RAJO, et al. An update of radiolabeled bombesin analogs for gastrin-releasing peptide receptor targeting. Curr Pharm Des. 2013;19(18):3329–41.

    CAS  PubMed  Google Scholar 

  19. Danhier F, Le Breton A, Preat V. RGD-Based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis. Mol Pharm. 2012;9(11):2961–73.

    CAS  PubMed  Google Scholar 

  20. Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10(1):9–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science. 1987;238(4826):491–7.

    CAS  PubMed  Google Scholar 

  22. Haubner R, Decristoforo C. Radiolabelled RGD peptides and peptidomimetics for tumour targeting. Front Biosci. 2009;14:872–86.

    CAS  Google Scholar 

  23. Gaertner FC, Kessler H, Wester HJ, Schwaiger M, Beer AJ. Radiolabelled RGD peptides for imaging and therapy. Eur J Nucl Med Mol Imaging. 2012;39:126–38.

    CAS  Google Scholar 

  24. Gagnon MKJ, Hausner SH, Marik J, Abbey CK, Marshall JF, Sutcliffe JL. High-throughput in vivo screening of targeted molecular imaging agents. Proc Natl Acad Sci U S A. 2009;106(42):17904–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Bandyopadhyay A, Raghavan S. Defining the role of integrin alpha(v)beta(6) in cancer. Curr Drug Targets. 2009;10(7):645–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Hackel BJ, Kimura RH, Miao Z, Liu H, Sathirachinda A, Cheng Z, et al. 18F-Fluorobenzoate-labeled cystine knot peptides for PET imaging of integrin alpha(v)beta(6). J Nucl Med. 2013;54(7):1101–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Hausner SH, Bauer N, Hu LY, Knight LM, Sutcliffe JL. The effect of bi-terminal PEGylation of an integrin alpha(v)beta(6)-targeted 18F peptide on pharmacokinetics and tumor uptake. J Nucl Med. 2015;56(5):784–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Li S, McGuire MJ, Lin M, Liu YH, Oyama T, Sun X, et al. Synthesis and characterization of a high-affinity alpha(v)beta(6)-specific ligand for in vitro and in vivo applications. Mol Cancer Ther. 2009;8(5):1239–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Charron CL, Hickey JL, Nsiama TK, Cruickshank DR, Turnbull WL, Luyt LG. Molecular imaging probes derived from natural peptides. Nat Prod Rep. 2016;33(6):761–800.

    CAS  PubMed  Google Scholar 

  30. Aumailley M, Gurrath M, Müller G, Calvete J, Timpl R, Kessler H. Arg-Gly-Asp constrained within cyclic pentapoptides. Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1. FEBS Lett. 1991;291(1):50–4.

    CAS  PubMed  Google Scholar 

  31. Ruoslahti E. RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol. 1996;12(1):697–715.

    CAS  PubMed  Google Scholar 

  32. Haubner R, Finsinger D, Kessler H. Stereoisomeric peptide libraries and peptidomimetics for designing selective inhibitors of the alpha(v)beta(3) integrin for a new cancer therapy. Angew Chem Int Ed Engl. 1997;36(1314):1374–89.

    CAS  Google Scholar 

  33. Burgus R, Ling N, Butcher M, Guillemin R. Primary structure of somatostatin, a hypothalamic peptide that inhibits the secretion of pituitary growth hormone. Proc Natl Acad Sci U S A. 1973;70(3):684–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Anastasi A, Erspamer V, Bucci M. Isolation and structure of bombesin and alytesin, two analogous active peptides from skin of European amphibians Bombina and Alytes. Experientia. 1971;27(2):166–7.

    CAS  PubMed  Google Scholar 

  35. Logan D, Abughazaleh R, Blakemore W, Curry S, Jackson T, King A, et al. Structure of a major immunogenic site on foot-and-mouth-disease virus. Nature. 1993;362(6420):566–8.

    CAS  PubMed  Google Scholar 

  36. Fani M, Maecke HR. Radiopharmaceutical development of radiolabelled peptides. Eur J Nucl Med Mol Imaging. 2012;39(S1):11–30.

    CAS  Google Scholar 

  37. Hu LY, Kelly KA, Sutcliffe JL. High-throughput approaches to the development of molecular imaging agents. Mol Imaging Biol. 2017;2:163–82.

    Google Scholar 

  38. Liu R, Li X, Xiao W, Lam KS. Tumor-targeting peptides from combinatorial libraries. Adv Drug Deliv Rev. 2017;110–111:13–37.

    PubMed  Google Scholar 

  39. Aina OH, Liu RW, Sutcliffe JL, Marik J, Pan CX, Lam KS. From combinatorial chemistry to cancer-targeting peptides. Mol Pharm. 2007;4(5):631–51.

    CAS  PubMed  Google Scholar 

  40. Amblard M, Fehrentz J-A, Martinez J, Subra G. Methods and protocols of modern solid phase peptide synthesis. Mol Biotechnol. 2006;33(3):239–54.

    CAS  PubMed  Google Scholar 

  41. Shelton PT, Jensen KJ. Linkers, resins, and general procedures for solid-phase peptide synthesis. In: Jensen KJ, Shelton PT, Pedersen S, editors. Peptide synthesis and applications. methods in molecular biology (methods and protocols), vol. 1047. Totowa: Humana Press; 2013. p. 23–41.

    Google Scholar 

  42. Koutsopoulos S. Peptide applications in biomedicine, biotechnology and bioengineering. Duxford: Woodhead Publishing; 2018.

    Google Scholar 

  43. Behrendt R, White P, Offer J. Advances in Fmoc solid-phase peptide synthesis. J Pept Sci. 2016;22(1):4–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Boas U, Mirsharghi S. Color test for selective detection of secondary amines on resin and in solution. Org Lett. 2014;16(22):5918–21.

    CAS  PubMed  Google Scholar 

  45. Galati R, Verdina A, Falasca G, Chersi A. Increased resistance of peptides to serum proteases by modification of their amino groups. Z Naturforsch C. 2003;58(7–8):558–61.

    CAS  PubMed  Google Scholar 

  46. Sutcliffe-Goulden JL, O’Doherty MJ, Marsden PK, Hart IR, Marshall JF, Bansal SS. Rapid solid phase synthesis and biodistribution of 18F-labelled linear peptides. Eur J Nucl Med Mol Imaging. 2002;29(6):754–9.

    CAS  PubMed  Google Scholar 

  47. Davis RA, Lau K, Hausner SH, Sutcliffe JL. Solid-phase synthesis and fluorine-18 radiolabeling of cycloRGDyK. Org Biomol Chem. 2016;14(37):8659–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Petrou C, Sarigiannis Y. Peptide synthesis: methods, trends, and challenges. In: Koutsopoulos S, editor. Peptide applications in biomedicine, biotechnology and bioengineering. Duxford: Woodhead Publishing; 2018. p. 1–21.

    Google Scholar 

  49. Zhang G, Annan RS, Carr SA, Neubert TA. Overview of peptide and protein analysis by mass spectrometry. Curr Protoc Mol Biol. 2014;108:10.21.1–10.21.30.

    Google Scholar 

  50. Beck JG, Frank AO, Kessler H. NMR of peptides. In: Bertini I, McGreevy KS, Parig G, editors. NMR of biomolecules. Weinheim: Wiley-VCH; 2012. p. 328–44.

    Google Scholar 

  51. Westermann JC, Craik DJ. NMR in peptide drug development. In: Otovos L, editor. Peptide-based drug design. Methods in molecular biology, vol. 494. Totowa: Humana Press; 2008. p. 87–113.

    Google Scholar 

  52. Sabet A, Biersack HJ, Ezziddin S. Advances in peptide receptor radionuclide therapy. Semin Nucl Med. 2016;46(1):40–6.

    PubMed  Google Scholar 

  53. Haubner R, Weber WA, Beer AJ, Vabuliene E, Reim D, Sarbia M, et al. Noninvasive visualization of the activated alpha(v)beta(3) integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD. PLoS Med. 2005;2(3):e70.

    PubMed  PubMed Central  Google Scholar 

  54. Kuchar M, Pretze M, Kniess T, Steinbach J, Pietzsch J, Löser R. Site-selective radiolabeling of peptides by 18F-fluorobenzoylation with [18F]SFB in solution and on solid phase: a comparative study. Amino Acids. 2012;43(4):1431–43.

    CAS  PubMed  Google Scholar 

  55. Richter S, Wuest F. 18F-Labeled peptides: The future is bright. Molecules. 2014;19(12):20536–56.

    PubMed  PubMed Central  Google Scholar 

  56. Eberle AN, Mild G. Receptor-mediated tumor targeting with radiopeptides. J Recept Signal Transduct Res. 2009;29(1):1–37.

    CAS  PubMed  Google Scholar 

  57. Miller PW, Long NJ, Vilar R, Gee AD. Synthesis of C-11, F-18, O-15, and N-13 radiolabels for positron emission tomography. Angew Chem Int Ed Engl. 2008;47(47):8998–9033.

    CAS  PubMed  Google Scholar 

  58. Link JM, Shoner SC, Krohn KA. Sources of carrier F-19 in F-18 fluoride. AIP Conf Proc. 2012;1509(61):61–5. https://doi.org/10.1063/1.4773941.

    Article  CAS  Google Scholar 

  59. Okarvi SM. Recent progress in fluorine-18 labelled peptide radiopharmaceuticals. Eur J Nucl Med. 2001;28(7):929–38.

    CAS  PubMed  Google Scholar 

  60. Olberg DE, Hjelstuen OK. Labeling strategies of peptides with 18F for positron emission tomography. Curr Top Med Chem. 2010;10(16):1669–79.

    CAS  PubMed  Google Scholar 

  61. Krishnan HS, Ma L, Vasdev N, Liang SH. 18F-Labeling of sensitive biomolecules for positron emission tomography. Chemistry. 2017;23(62):15553–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Vaidyanathan G, Zalutsky MR. Synthesis of N-succinimidyl 4-[18F]fluorobenzoate, an agent for labeling proteins and peptides with 18F. Nat Protoc. 2006;1(4):1655–61.

    CAS  PubMed  Google Scholar 

  63. Namavari M, Cheng Z, Zhang R, De A, Levi J, Hoerner JK, et al. A novel method for direct site-specific radiolabeling of peptides using [18F]FDG. Bioconjug Chem. 2009;20(3):432–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Carberry P, Carpenter AP, Kung HF. Fluoride-18 radiolabeling of peptides bearing an aminooxy functional group to a prosthetic ligand via an oxime bond. Bioorg Med Chem Lett. 2011;21(23):6992–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Hausner SH, Marik J, Gagnon MKJ, Sutcliffe JL. In vivo positron emission tomography (PET) imaging with an alpha(v)beta(6) specific peptide radiolabeled using 18F-“click” chemistry: Evaluation and comparison with the corresponding 4-[18F]fluorobenzoyl- and 2-[18F]fluoropropionyl-peptides. J Med Chem. 2008;51(19):5901–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Vaidyanathan G, Zalutsky MR. Labeling proteins with fluorine-18 using N-succinimidyl 4-[18F]fluorobenzoate. Int J Rad Appl Instrum B. 1992;19(3):275–81.

    CAS  PubMed  Google Scholar 

  67. Thonon D, Goblet D, Goukens E, Kaisin G, Paris J, Aerts J, et al. Fully automated preparation and conjugation of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) with RGD peptide using a GE FASTlab synthesizer. Mol Imaging Biol. 2011;13(6):1088–95.

    PubMed  Google Scholar 

  68. Mäding P, Füchtner F, Wüst F. Module-assisted synthesis of the bifunctional labelling agent N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB). Appl Radiat Isot. 2005;63(3):329–32.

    PubMed  Google Scholar 

  69. Haka MS, Kilbourn MR, Watkins GL, Toorongian SA. Aryltrimethylammonium trifluoromethanesulfonates as precursors to aryl [18F]fluorides: Improved synthesis of [18F]GBR-13119. J Labelled Comp Radiopharm. 1989;27(7):823–33.

    CAS  Google Scholar 

  70. Basuli F, Zhang X, Woodroofe CC, Jagoda EM, Choyke PL, Swenson RE. Fast indirect fluorine-18 labeling of protein/peptide using the useful 6-fluoronicotinic acid-2,3,5,6-tetrafluorophenyl prosthetic group: A method comparable to direct fluorination. J Labelled Comp Radiopharm. 2017;60(3):168–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Olberg DE, Arukwe JM, Grace D, Hjelstuen OK, Solbakken M, Kindberg GM, et al. One step radiosynthesis of 6-[18F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([18F]F-Py-TFP): A new prosthetic group for efficient labeling of biomolecules with fluorine-18. J Med Chem. 2010;53(4):1732–40.

    CAS  PubMed  Google Scholar 

  72. Wu Z, Li Z-B, Chen X. 18F-labeling of peptides using FBEM. Protoc Exch. 2007; https://doi.org/10.1038/nprot.2007.286.

  73. Wuest F, Köhler L, Berndt M, Pietzsch J. Systematic comparison of two novel, thiol-reactive prosthetic groups for 18F labeling of peptides and proteins with the acylation agent succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). Amino Acids. 2009;36(2):283–95.

    CAS  PubMed  Google Scholar 

  74. White JB, Hausner SH, Carpenter RD, Sutcliffe JL. Optimization of the solid-phase synthesis of F-18 radiolabeled peptides for positron emission tomography. Appl Radiat Isot. 2012;70(12):2720–9.

    CAS  PubMed  Google Scholar 

  75. Bernard-Gauthier V, Lepage ML, Waengler B, Bailey JJ, Liang SH, Perrin DM, et al. Recent advances in F-18 radiochemistry: a focus on B-18F, Si-18F, Al-18F, and C-18F radiofluorination via spirocyclic iodonium ylides. J Nucl Med. 2018;59(4):568–72.

    CAS  PubMed  Google Scholar 

  76. Smith GE, Sladen HL, Biagini SC, Blower PJ. Inorganic approaches for radiolabelling biomolecules with fluorine-18 for imaging with positron emission tomography. Dalton Trans. 2011;40(23):6196–205.

    CAS  PubMed  Google Scholar 

  77. Bernard-Gauthier V, Wängler C, Schirrmacher E, Kostikov A, Jurkschat K, Wängler B, et al. 18F-labeled silicon-based fluoride acceptors: potential opportunities for novel positron emitting radiopharmaceuticals. Biomed Res Int. 2014;2014:1–20.

    Google Scholar 

  78. Wangler C, Niedermoser S, Chin J, Orchowski K, Schirrmacher E, Jurkschat K, et al. One-step 18F-labeling of peptides for positron emission tomography imaging using the SiFA methodology. Nat Protoc. 2012;7(11):1946–55.

    PubMed  Google Scholar 

  79. Liu Z, Pourghiasian M, Radtke MA, Lau J, Pan J, Dias GM, et al. An organotrifluoroborate for broadly applicable one-step 18F-labeling. Angew Chem Int Ed Engl. 2014;53(44):11876–80.

    CAS  PubMed  Google Scholar 

  80. McBride WJ, Sharkey RM, Goldenberg DM. Radiofluorination using aluminum-fluoride (Al18F). EJNMMI Res. 2013;3(1):36.

    PubMed  PubMed Central  Google Scholar 

  81. Marik J, Sutcliffe JL. Click for PET: rapid preparation of [18F]fluoropeptides using CuI catalyzed 1,3-dipolar cycloaddition. Tetrahedron Lett. 2006;47(37):6681–4.

    CAS  Google Scholar 

  82. Glaser M, Årstad E. “Click labeling” with 2-[18F]fluoroethylazide for positron emission tomography. Bioconjug Chem. 2007;18(3):989–93.

    CAS  PubMed  Google Scholar 

  83. Zeng D, Zeglis BM, Lewis JS, Anderson CJ. The growing impact of bioorthogonal click chemistry on the development of radiopharmaceuticals. J Nucl Med. 2013;54(6):829–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Pretze M, Pietzsch D, Mamat C. Recent trends in bioorthogonal click-radiolabeling reactions using fluorine-18. Molecules. 2013;18(7):8618–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Kettenbach K, Schieferstein H, Ross TL. 18F-labeling using click cycloadditions. Biomed Res Int. 2014;2014:1–16.

    Google Scholar 

  86. Denk C, Svatunek D, Filip T, Wanek T, Lumpi D, Fröhlich J, et al. Development of a 18F-labeled tetrazine with favorable pharmacokinetics for bioorthogonal PET imaging. Angew Chem Int Ed Engl. 2014;53:9655–9.

    CAS  PubMed  Google Scholar 

  87. Lazari M, Collins J, Shen B, Farhoud M, Yeh D, Maraglia B, et al. Fully automated production of diverse 18F-labeled PET tracers on the ELIXYS multireactor radiosynthesizer without hardware modification. J Nucl Med Technol. 2014;42(3):203–10.

    PubMed  PubMed Central  Google Scholar 

  88. Collet C, Maskali F, Clement A, Chretien F, Poussier S, Karcher G, et al. Development of 6-[18F]fluoro-carbohydrate-based prosthetic groups and their conjugation to peptides via click chemistry. J Labelled Comp Radiopharm. 2016;59(2):54–62.

    CAS  PubMed  Google Scholar 

  89. Jacobson O, Yan X, Ma Y, Niu G, Kiesewetter DO, Chen X. Novel method for radiolabeling and dimerizing thiolated peptides using [18F]-hexafluorobenzene. Bioconjug Chem. 2015;26(10):2016–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Ackermann U, Plougastel L, Goh YW, Yeoh SD, Scott AM. Improved synthesis of [18F]FLETT via a fully automated vacuum distillation method for [18F]2-fluoroethyl azide purification. Appl Radiat Isot. 2014;94:72–6.

    CAS  PubMed  Google Scholar 

  91. Ackermann U, Plougastel L, Wichmann C, Goh YW, Yeoh SD, Poniger SS, et al. Fully automated synthesis and coupling of [18F]FBEM to glutathione using the iPHASE FlexLab module. J Labelled Comp Radiopharm. 2014;57(2):115–20.

    CAS  PubMed  Google Scholar 

  92. Zeglis BM, Lewis JS. A practical guide to the construction of radiometallated bioconjugates for positron emission tomography. Dalton Trans. 2011;40(23):6168–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Wadas TJ, Wong EH, Weisman GR, Anderson CJ. Coordinating radiometals of copper, gallium, indium, yttrium, and zirconium for PET and SPECT imaging of disease. Chem Rev. 2010;110(5):2858–902.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Färber SF, Wurzer A, Reichart F, Beck R, Kessler H, Wester H-J, et al. Therapeutic radiopharmaceuticals targeting integrin alpha(v)beta(6). ACS Omega. 2018;3(2):2428–36.

    PubMed  PubMed Central  Google Scholar 

  95. Roosenburg S, Laverman P, Joosten L, Cooper MS, Kolenc-Peitl PK, Foster JM, et al. PET and SPECT imaging of a radiolabeled minigastrin analogue conjugated with DOTA, NOTA, and NODAGA and labeled with 64Cu, 68Ga, and 111In. Mol Pharm. 2014;11(11):3930–7.

    CAS  PubMed  Google Scholar 

  96. Hu LY, Bauer N, Knight LM, Li Z, Liu S, Anderson CJ, et al. Characterization and evaluation of 64Cu-labeled A20FMDV2 conjugates for imaging the integrin alpha(v)beta(6). Mol Imaging Biol. 2014;16(4):567–77.

    PubMed  PubMed Central  Google Scholar 

  97. Lin M, Welch MJ, Lapi SE. Effects of chelator modifications on 68Ga-labeled [Tyr3]octreotide conjugates. Mol Imaging Biol. 2013;15(5):606–13.

    PubMed  PubMed Central  Google Scholar 

  98. Cai Z, Anderson CJ. Chelators for copper radionuclides in positron emission tomography radiopharmaceuticals. J Labelled Comp Radiopharm. 2014;57(4):224–30.

    CAS  PubMed  Google Scholar 

  99. De León-Rodríguez LM, Kovacs Z. The synthesis and chelation chemistry of DOTA−peptide conjugates. Bioconjug Chem. 2008;19(2):391–402.

    PubMed  Google Scholar 

  100. Liu S, Edwards DS. Stabilization of 90Y-labeled DOTA-biomolecule conjugates using gentisic acid and ascorbic acid. Bioconjug Chem. 2001;12(4):554–8.

    CAS  PubMed  Google Scholar 

  101. Banerjee S, Pillai MRA, Knapp FF. Lutetium-177 therapeutic radiopharmaceuticals: Linking chemistry, radiochemistry, and practical applications. Chem Rev. 2015;115(8):2934–74.

    CAS  PubMed  Google Scholar 

  102. Kiesewetter DO, Gao H, Ma Y, Niu G, Quan Q, Guo N, et al. 18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma. Eur J Nucl Med Mol Imaging. 2011;39(3):463–73.

    PubMed  PubMed Central  Google Scholar 

  103. James ML, Gambhir SS. A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012;92(2):897–965.

    CAS  PubMed  Google Scholar 

  104. Bigott-Hennkens HM, Dannoon S, Lewis MR, Jurisson SS. In vitro receptor binding assays: general methods and considerations. Q J Nucl Med Mol Imaging. 2008;52(3):245–53.

    CAS  PubMed  Google Scholar 

  105. Jenssen H, Aspmo SI. Serum stability of peptides. In: Otvos L, editor. Peptide-based drug design. Methods In molecular biology, vol. 494. Totowa: Humana Press; 2008. p. 177–86.

    Google Scholar 

  106. Hein P, Michel MC, Leineweber K, Wieland T, Wettschureck N, Offermanns S. Receptor and binding studies. In: Dhein S, Mohr FW, Delmar M, editors. Practical methods in cardiovascular research. Berlin: Springer; 2005. p. 723–83.

    Google Scholar 

  107. Walker MW, Miller RJ. 125I-neuropeptide Y and 125I-peptide YY bind to multiple receptor sites in rat brain. Mol Pharm. 1988;34(6):779–92.

    CAS  Google Scholar 

  108. Waterhouse R. Determination of lipophilicity and its use as a predictor of blood–brain barrier penetration of molecular imaging agents. Mol Imaging Biol. 2003;5(6):376–89.

    Google Scholar 

  109. Richter S, Wuest M, Bergman CN, Way JD, Krieger S, Rogers BE, et al. Rerouting the metabolic pathway of 18F-labeled peptides: the influence of prosthetic groups. Bioconjug Chem. 2015;26(2):201–12.

    CAS  PubMed  Google Scholar 

  110. Stout DB, Chatziioannou AF, Lawson TP, Silverman RW, Gambhir SS, Phelps ME. Small animal imaging center design: the facility at the UCLA Crump Institute for Molecular Imaging. Mol Imaging Biol. 2005;7(6):393–402.

    PubMed  PubMed Central  Google Scholar 

  111. David JM, Knowles S, Lamkin DM, Stout DB. Individually ventilated cages impose cold stress on laboratory mice: a source of systemic experimental variability. J Am Assoc Lab Anim Sci. 2013;52(6):738–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Keyes JW Jr. SUV: standard uptake or silly useless value? J Nucl Med. 1995;36(10):1836–9.

    PubMed  Google Scholar 

  113. Visser EP, Boerman OC, Oyen WJG. SUV: from silly useless value to smart uptake value. J Nucl Med. 2010;51(2):173–5.

    PubMed  Google Scholar 

  114. Pompili L, Porru M, Caruso C, Biroccio A, Leonetti C. Patient-derived xenografts: a relevant preclinical model for drug development. J Exp Clin Cancer Res. 2016;35(189):1–8.

    Google Scholar 

  115. Jackson SJ, Thomas GJ. Human tissue models in cancer research: looking beyond the mouse. Dis Model Mech. 2017;10(8):939–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Randall EK. PET-computed tomography in veterinary medicine. Vet Clin North Am Small Anim Pract. 2016;46(3):515–33.

    PubMed  Google Scholar 

  117. Spriet M, Espinosa P, Kyme AZ, Phillips KL, Katzman SA, Galuppo LD, et al. 18F-sodium fluoride positron emission tomography of the equine distal limb: exploratory study in three horses. Equine Vet J. 2018;50:125–32.

    CAS  PubMed  Google Scholar 

  118. Akizawa H, Uehara T, Arano Y. Renal uptake and metabolism of radiopharmaceuticals derived from peptides and proteins. Adv Drug Deliv Rev. 2008;60(12):1319–28.

    CAS  PubMed  Google Scholar 

  119. Sleep D. Albumin and its application in drug delivery. Expert Opin Drug Deliv. 2014;12(5):793–812.

    PubMed  Google Scholar 

  120. Nock BA, Maina T, Krenning EP, de Jong M. “To serve and protect”: enzyme inhibitors as radiopeptide escorts promote tumor targeting. J Nucl Med. 2013;55(1):121–7.

    PubMed  Google Scholar 

  121. Pless J. The history of somatostatin analogs. J Endocrinol Invest. 2005;28(11 Suppl International):1–4.

    CAS  PubMed  Google Scholar 

  122. Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, et al. Hypothalamic polypeptide that inhibits secretion of immunoreactive pituitary growth-gormone. Science. 1973;179(4068):77–9.

    CAS  PubMed  Google Scholar 

  123. Okarvi SM. Peptide-based radiopharmaceuticals and cytotoxic conjugates: potential tools against cancer. Cancer Treat Rev. 2008;34(1):13–26.

    CAS  PubMed  Google Scholar 

  124. Martino MCD, Hofland LJ, Lamberts SWJ. Somatostatin and somatostatin receptors: from basic concepts to clinical applications. In: Martini L, editor. Progress in brain research, vol. 182. Amsterdam: Elsevier; 2010. p. 255–80.

    Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, University of California Davis, Sacramento, CA, USA

    Ryan A. Davis & Sven H. Hausner

  2. Department of Internal Medicine and Department of Biomedical Engineering, University of California Davis, Sacramento, CA, USA

    Julie L. Sutcliffe

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  1. Ryan A. Davis
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  2. Sven H. Hausner
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  3. Julie L. Sutcliffe
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Correspondence to Julie L. Sutcliffe .

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Editors and Affiliations

  1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jason S. Lewis

  2. Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

    Albert D. Windhorst

  3. Department of Chemistry, Hunter College, City University of New York, New York, NY, USA

    Brian M. Zeglis

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Davis, R.A., Hausner, S.H., Sutcliffe, J.L. (2019). Peptides as Radiopharmaceutical Vectors. In: Lewis, J., Windhorst, A., Zeglis, B. (eds) Radiopharmaceutical Chemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-98947-1_8

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