Skip to main content
SpringerLink
Log in

Radiotracer II: Peptide-Based Radiopharmaceuticals

  • Chapter
Small Animal Imaging

Abstract

Recently, radiolabeled receptor-binding peptides have emerged as an important class of radiopharmaceuticals for diagnosis and therapy. Major advantages of peptides compared with antibodies are that they are not immunogenic, show fast diffusion and target localization and can be modified concerning metabolic stability and pharmacokinetics. Advantages compared to small molecular weight compounds are, that they are more tolerant concerning modification necessary for appropriate labeling (e.g., introduction of chelating systems for radio metalation) and strategies for optimizing pharmacokinetics. Most prominent members of this class of tracer are radiolabeled peptides for targeting somatostatin receptors. Some of them are already clinical routine for diagnosis as well as peptide receptor radionuclide therapy of somatostatin expressing tumors. Currently a variety of other peptides including bombesin derivatives, cholecystokinin/gastrin analogs and RGD-containing peptides are evaluated.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 179.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bakker WH, Albert R, Bruns C et al (1991) [111In-DTPA-dPhe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation. Life Sci 49:1583–1591

    Article  PubMed  CAS  Google Scholar 

  • Breeman WA, De Jong M, Visser TJ et al (2003) Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur J Nucl Med Mol Imaging 30:917–920

    Article  PubMed  CAS  Google Scholar 

  • Brissette R, Goldstein NI (2007) The use of phage display peptide libraries for basic and translational research. Methods Mol Biol 383:203–213

    PubMed  CAS  Google Scholar 

  • Chen X, Park R, Hou Y et al (2004a) Micropet imaging of brain tumor angiogenesis with 18F-labeled pegylated rgd peptide. Eur J Nucl Med Mol Imaging 31:1081–1089

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Park R, Shahinian AH et al (2004b) Pharmacokinetics and tumor retention of 125I-labeled rgd peptide are improved by PEGylation. Nucl Med Biol 31:11–19

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Park R, Tohme M et al (2004c) Micropet and autoradiographic imaging of breast cancer alpha v-integrin expression using 18F- and 64Cu-labeled RGD peptide. Bioconjug Chem 15:41–49

    Article  PubMed  Google Scholar 

  • Chighine A, Sechi G, Bradley M (2007) Tools for efficient high-throughput synthesis. Drug Discov Today 12:459–464

    Article  PubMed  CAS  Google Scholar 

  • Coenen HH, Mertens J, Maziere B (2006) Radioiodination reactions for pharmaceuticals – compendium for effective synthesis strategies. Springer, Dordrecht

    Book  Google Scholar 

  • Decristoforo C, Mather SJ (1999a) 99m-Technetium-labelled peptide-HYNIC conjugates: effects of lipophilicity and stability on biodistribution. Nucl Med Biol 26:389–396

    Article  PubMed  CAS  Google Scholar 

  • Decristoforo C, Mather SJ (1999b) Technetium-99m somatostatin analogues: effect of labelling methods and peptide sequence. Eur J Nucl Med 26:869–876

    Article  PubMed  CAS  Google Scholar 

  • Decristoforo C, Faintuch-Linkowski B, Rey A et al (2006) [99mTc]HYNIC-RGD for imaging integrin alpha(v)beta3 expression. Nucl Med Biol 33:945–952

    Article  PubMed  CAS  Google Scholar 

  • Decristoforo C, Hernandez Gonzalez I, Carlsen J et al (2008) 68Ga- and 111In-labelled DOTA-RGD peptides for imaging of alpha(v)beta3 integrin expression. Eur J Nucl Med Mol Imaging 35:1507–1515

    Article  PubMed  Google Scholar 

  • Egli A, Alberto R, Tannahill L et al (1999) Organometallic 99mTc-aquaion labels peptide to an unprecedented high specific activity. J Nucl Med 40:1913–1917

    PubMed  CAS  Google Scholar 

  • Eisenwiener KP, Prata MI, Buschmann I et al (2002) NODAGATOC, a new chelator-coupled somatostatin analogue labeled with [67/68Ga] and [111In] for SPECT, PET, and targeted therapeutic applications of somatostatin receptor (hsst2) expressing tumors. Bioconjug Chem 13:530–541

    Article  PubMed  CAS  Google Scholar 

  • Feher M, Schmidt JM (2003) Property distributions: Differences between drugs, natural products, and molecules from combinatorial chemistry. J Chem Inf Comput Sci 43:218–227

    Article  PubMed  CAS  Google Scholar 

  • Froidevaux S, Eberle AN, Christe M et al (2002) Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model. Int J Cancer 98:930–937

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Garayoa E, Blauenstein P, Blanc A et al (2009) A stable neurotensin-based radiopharmaceutical for targeted imaging and therapy of neurotensin receptor-positive tumours. Eur J Nucl Med Mol Imaging 36:37–47

    Article  PubMed  CAS  Google Scholar 

  • Garrison JC, Rold TL, Sieckman GL et al (2007) In vivo evaluation and small-animal pet/ct of a prostate cancer mouse model using 64Cu bombesin analogs: Side-by-side comparison of the CB-TE2A and DOTA chelation systems. J Nucl Med 48:1327–1337

    Article  PubMed  CAS  Google Scholar 

  • Handl HL, Vagner J, Han H et al (2004) Hitting multiple targets with multimeric ligands. Expert Opin Ther Targets 8:565–586

    Article  PubMed  CAS  Google Scholar 

  • Harris JM, Chess RB (2003) Effect of PEGylation on pharmaceuticals. Nat Rev Drug Discov 2:214–221

    Article  PubMed  CAS  Google Scholar 

  • Haubner R, Decristoforo C (2009) Radiolabelled RGD peptides and peptidomimetics for tumour targeting. Front Biosci 14:872–886

    Article  CAS  Google Scholar 

  • Haubner R, Wester HJ, Burkhart F et al (2001a) Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med 42:326–336

    PubMed  CAS  Google Scholar 

  • Haubner R, Wester HJ, Weber WA et al (2001b) Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res 61:1781–1785

    PubMed  CAS  Google Scholar 

  • Hausner SH, Kukis DL, Gagnon MK et al (2009) Evaluation of [64Cu]Cu -DOTA and [64Cu]Cu-CB-TE2A chelates for targeted positron emission tomography with an alpha(v)beta(6)-specific peptide. Mol Imaging 8:111–121

    PubMed  CAS  Google Scholar 

  • Heppeler A, Froidevaux S, Eberle AN et al (2000) Receptor targeting for tumor localisation and therapy with radiopeptides. Curr Med Chem 7:971–994

    Article  PubMed  CAS  Google Scholar 

  • Hultsch C, Schottelius M, Auernheimer J et al (2009) 18F-fluoroglucosylation of peptides, exemplified on cyclo(RGDfK). Eur J Nucl Med Mol Imaging 36(9):1469–1474

    Google Scholar 

  • Janssen ML, Oyen WJ, Dijkgraaf I et al (2002) Tumor targeting with radiolabeled alpha(v)beta3 integrin binding peptides in a nude mouse model. Cancer Res 62:6146–6151

    PubMed  CAS  Google Scholar 

  • Leach AR, Harren J (2007) Structure-based drug discovery. Springer, Berlin

    Google Scholar 

  • Maina T, Nock B, Nikolopoulou A et al (2002) [99mTc]Demotate, a new 99mTc-based [Tyr3]octreotate analogue for the detection of somatostatin receptor-positive tumours: synthesis and preclinical results. Eur J Nucl Med Mol Imaging 29:742–753

    Article  PubMed  CAS  Google Scholar 

  • Maschauer S, Prante O (2009) A series of 2-o-trifluoromethylsulfonyl-d-mannopyranosides as precursors for concomitant 18F-labeling and glycosylation by click chemistry. Carbohydr Res 344:753–761

    Article  PubMed  CAS  Google Scholar 

  • Mindt TL, Struthers H, Brans L et al (2006) “Click to chelate”: synthesis and installation of metal chelates into biomolecules in a single step. J Am Chem Soc 128:15096–15097

    Article  PubMed  CAS  Google Scholar 

  • Nicole P, Lins L, Rouyer-Fessard C et al (2000) Identification of key residues for interaction of vasoactive intestinal peptide with human Vpac1 and Vpac2 receptors and development of a highly selective vpac1 receptor agonist. Alanine scanning and molecular modeling of the peptide. J Biol Chem 275:24003–24012

    Article  PubMed  CAS  Google Scholar 

  • Okarvi SM (2001) Recent progress in fluorine-18 labelled peptide radiopharmaceuticals. Eur J Nucl Med 28:929–938

    Article  PubMed  CAS  Google Scholar 

  • Poethko T, Schottelius M, Thumshirn G et al (2004a) Chemoselective pre-conjugate radiohalogenation of unprotected mono- and multimeric peptides via oxime formation. Radiochimica Acta 92:317–327

    Article  CAS  Google Scholar 

  • Poethko T, Schottelius M, Thumshirn G et al (2004b) Two-step methodology for high-yield routine radiohalogenation of peptides: 18F-labeled RGD and octreotide analogs. J Nucl Med 45:892–902

    PubMed  CAS  Google Scholar 

  • Prante O, Einsiedel J, Haubner R et al (2007) 3, 4, 6-tri-o-acetyl-2-deoxy-2-[18F]fluoroglucopyranosyl phenylthiosulfonate: a thiol-reactive agent for the chemoselective 18F-glycosylation of peptides. Bioconjug Chem 18: 254–262

    Article  PubMed  CAS  Google Scholar 

  • Schibli R, La Bella R, Alberto R et al (2000) Influence of the denticity of ligand systems on the in vitro and in vivo behavior of 99mTc(I)-tricarbonyl complexes: a hint for the future functionalization of biomolecules. Bioconjug Chem 11:345–351

    Article  PubMed  CAS  Google Scholar 

  • Schottelius M, Rau F, Reubi JC et al (2005) Modulation of pharmacokinetics of radioiodinated sugar-conjugated somatostatin analogues by variation of peptide net charge and carbohydration chemistry. Bioconjug Chem 16:429–437

    Article  PubMed  CAS  Google Scholar 

  • Smith-Jones PM, Stolz B, Bruns C et al (1994) Gallium-67/gallium-68-[DFO]-octreotide–a potential radiopharmaceutical for pet imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in vitro and preliminary in vivo studies. J Nucl Med 35:317–325

    PubMed  CAS  Google Scholar 

  • Thonon D, Kech C, Paris J et al (2009) New strategy for the preparation of clickable peptides and labeling with 1-(azidomethyl)-4-[18F]-fluorobenzene for PET. Bioconjug Chem 20:817–823

    Article  PubMed  CAS  Google Scholar 

  • Trepel M, Arap W, Pasqualini R (2002) In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr Opin Chem Biol 6:399–404

    Article  PubMed  CAS  Google Scholar 

  • Vagner J, Qu H, Hruby VJ (2008) Peptidomimetics, a synthetic tool of drug discovery. Curr Opin Chem Biol 12:292–296

    Article  PubMed  CAS  Google Scholar 

  • Vallabhajosula S, Moyer BR, Lister-James J et al (1996) Preclinical evaluation of technetium-99m-labeled somatostatin receptor-binding peptides. J Nucl Med 37:1016–1022

    PubMed  CAS  Google Scholar 

  • Velikyan I, Beyer GJ, Langstrom B (2004) Microwave-supported preparation of 68Ga bioconjugates with high specific radioactivity. Bioconjug Chem 15:554–560

    Article  PubMed  CAS  Google Scholar 

  • Wester HJ, Schottelius M (2007) Fluorine-18 labeling of peptides and proteins. In: Schubiger AP, Lehmann L, Friebe M (eds) PET chemistry – the driving force in molecular imaging. Springer, Berlin

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Roland Haubner & Clemens Decristoforo

Authors
  1. Roland Haubner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clemens Decristoforo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roland Haubner .

Editor information

Editors and Affiliations

  1. Chair of Experimental Molecular Imaging, University of Aachen (RWTH), Pauwelsstraße 20, Aachen, 52074, Germany

    Fabian Kiessling

  2. Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Department of Radiology, Eberhard Karls University of Tübingen, Röntgenweg 13, Tübingen, 72076, Germany

    Bernd J. Pichler

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Haubner, R., Decristoforo, C. (2011). Radiotracer II: Peptide-Based Radiopharmaceuticals. In: Kiessling, F., Pichler, B. (eds) Small Animal Imaging. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12945-2_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-12945-2_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-12944-5

  • Online ISBN: 978-3-642-12945-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation