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Molecular Imaging pp 43–72Cite as

Radiolabeled Peptides in Nuclear Oncology: Influence of Peptide Structure and Labeling Strategy on Pharmacology

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Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 49))

3.5 Summary and Conclusions

Radiometallo-labeled analogs of SS have shown great benefit in the in vivo localization and targeted radiotherapy of human tumors. The progress and innovation in this clinical application came from the change in strategy, leaving the most widely used radiohalogens for a coordination chemistry approach. The use of chelators appended to the biologically active peptide which convey high thermodynamic and kinetic stability to the radiopeptides did not only improve the pharmacokinetics and pharmacodynamics of the molecules, but surprisingly the biological potency as well.

The most urgent problem to be solved in the field is to improve the kidney clearance of the radiopeptides. The kidney turned out to be the dose-limiting organ in this type of targeted radiotherapy. Coordination chemical strategies have already paved the way to a successful clinical application; it is most likely that chelator modification will further help to improve the renal handling of radiometallo-peptides.

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References

  • Abrams MJ, Juweid M, tenKate CI, Schwartz DA, Hauser MM, Gaul FE, Fuccello AJ, Rubin RH, Strauss HW, Fischman AJ (1990) Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats. J Nucl Med 31: 2022–2028

    PubMed  CAS  Google Scholar 

  • Achilefu S, Wilhelm RR, Jimenez HN, Schmidt MA, Srinivasan A (2000) A new method for the synthesis of tri-tert-butyl diethylenetriaminepenta-acetic acid and its derivatives. J Org Chem 65:1562–1565

    Article  PubMed  CAS  Google Scholar 

  • Albert R, Smith-Jones P, Stolz B, Simeon C, Knecht H, Brans C, Pless J (1998) Direct synthesis of [DOTA-DPhe1]-octreotide and [DOTA-DPhe1,Tyr3]-octreotide (SMT487): two conjugates for systemic delivery of radiotherapeutical nuclides to somatostatin receptor positive tumors in man. Bioorg Med Chem Lett 8:1207–1210

    Article  PubMed  CAS  Google Scholar 

  • Andre J, Maecke H, Zehnder M, Macko L, Akyel K (1998) 1,4,7-Triazacy-clononane-1-succinic acid-4,7-diacetic acid (NODASA): a new bifunctional chelator for radio gallium-labelling of biomolecules. Chem Commun 12:1301–1302

    Article  Google Scholar 

  • Blower PJ, Lewis JS, Zweit J (1996) Copper radionuclides and radiopharmaceuticals in nuclear medicine. Nucl Med Biol 23:957–980

    Article  PubMed  CAS  Google Scholar 

  • Cutler CS, Smith CJ, Ehrhardt GJ, Tyler TT, Jurisson SS, Deutsch E (2000) Current and potential therapeutic uses of lanthanide radioisotopes. Cancer Biother Radiopharm 15:531–545

    Article  PubMed  CAS  Google Scholar 

  • de Jong M, Bakker WH, Krenning EP, Breeman WA, van der Pluijm ME, Bernard BF, Visser TJ, Jermann E, Béhé M, Powell P, Maecke HR (1997) Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,D-Phe1,Tyr3]octreotide, a promising somatostatin analog for radionuclide therapy. Eur J Nucl Med 24:368–371

    Article  PubMed  Google Scholar 

  • de Jong M, Breeman WA, Bernard BF, Bakker WH, Schaar M, van Gameren A, Bugaj JE, Erion J, Schmidt M, Srinivasan A, Krenning EP (2001) [177Lu-DOTA0,Tyr3] octreotate for somatostatin receptor-targeted radionuclide therapy. Int J Cancer 92:628–633

    Article  PubMed  Google Scholar 

  • Edwards DS, Liu S, Barrett JA, Harris AR, Looby RJ, Ziegler MC, Hemingway SJ, Carroll TR (1997) New and versatile ternary ligand system for technetium radiopharmaceuticals: water soluble phosphines and tricine as coligands in labeling a hydrazinonicotinamide-modified cyclic glycopro-tein IIb/IIIa receptor antagonist with 99mTc. Bioconjug Chem 8:146–154

    Article  PubMed  CAS  Google Scholar 

  • Eisenwiener KP (2001) Synthese von makrozyklischen Prochelatoren und ihre Evaluation im Tumortargeting mit regulatorischen Peptiden und im Bereich der Entwicklung neuer auf Gd(III) basierender MRI-Kontrastmit-tel. PhD thesis: University of Basel

    Google Scholar 

  • Eisenwiener KP, Powell P, Macke HR (2000) A convenient synthesis of novel bifunctional prochelators for coupling to bioactive peptides for radiometal labelling. Bioorg Med Chem Lett 10:2133–2135

    Article  PubMed  CAS  Google Scholar 

  • Eisenwiener KP, Prata MI, Buschmann I, Zhang HW, Santos AC, Wenger S, Reubi JC, Macke HR (2002) NODAGATOC, a new chelator-coupled somatostatin analog 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 

  • Fischman AJ, Babich JW, Strauss HW (1993) A ticket to ride: peptide radiopharmaceuticals. J Nucl Med 34:2253–2263

    PubMed  CAS  Google Scholar 

  • Heppeler A (2000) Auswirkungen von Metallkomplexgeometrien verschiedener makrozyklischer Polyaminopolycarboxylat Chelatoren auf die Biologie und Pharmakologie von Metall-Peptid Konjugaten. PhD thesis, University of Basel

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Heppeler A, Froidevaux S, Mäcke HR, Jermann E, Béhé M, Powell P, Hennig M (1999) Radiometal-labelled macrocyclic chelator-derivatized somatostatin analog with superb tumour-targeting properties and potential for receptor-mediated internal radiotherapy. Chem Eur J 5:1016–1023

    Article  Google Scholar 

  • Hu F, Cutler CS, Hoffman T, Sieckman G, Volkert WA, Jurisson SS (2002) Pm-149 DOTA bombesin analogs for potential radiotherapy, in vivo comparison with Sm-153 and Lu-177 labeled DO3A-amide-βAla-BBN(7–14) NH2. Nucl Med Biol 29:423–430

    Article  PubMed  CAS  Google Scholar 

  • Humm JL (1986) Dosimetric aspects of radiolabeled antibodies for tumor therapy. J Nucl Med 27:1490–1497

    PubMed  CAS  Google Scholar 

  • Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, Schmidt MA, Bugaj JL, de Jong M, Krenning EP (2001) [177Lu-DOTA0Tyr3]octreotate: comparison with [111In-DTPA0]octreotide in patients. Eur J Nucl Med 28:1319–1325

    Article  PubMed  CAS  Google Scholar 

  • Lamberts SW, Bakker WH, Reubi JC, Krenning EP (1990) Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med 323:1246–1249

    Article  PubMed  CAS  Google Scholar 

  • Lister-James J, Moyer BR, Dean T (1996) Small peptides radiolabeled with 99mTc. Q J Nucl Med 40:221–233

    PubMed  CAS  Google Scholar 

  • Liu S, Edwards DS (1999) 99mTc-labeled small peptides as diagnostic radio-pharmaceuticals. Chem Rev 99:2235–2268

    Article  PubMed  CAS  Google Scholar 

  • Maecke H, Scherer G, Heppeler A, Hennig M (2001) Is In-111 an ideal surrogate for Y-90? If not, why? Eur J Nucl Med 28:967

    Google Scholar 

  • Maecke HR, Riesen A, Ritter W (1989) The molecular structure of indium-DTPA. J Nucl Med 30:1235–1239

    PubMed  CAS  Google Scholar 

  • Maina T, Nock B, Nikolopoulou A, Sotiriou P, Loudos G, Maintas D, Cor-dopatis P, Chiotellis E (2002) [99mTc]Demotate, a new 99mTc-based [Tyr3]octreotate analog 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 

  • McDevitt MR, Ma D, Lai LT, Simon J, Borchardt P, Frank RK, Wu K, Pellegrini V, Curcio MJ, Miederer M, Bander NH, Scheinberg DA (2001) Tumor therapy with targeted atomic nanogenerators. Science 294:1537–1540

    Article  PubMed  CAS  Google Scholar 

  • Patel Y (1999) Somatostatin and its receptor family. Front Neuroendocrinol 20:157–198

    Article  PubMed  CAS  Google Scholar 

  • Reisine T, Bell G (1995) Molecular biology of somatostatin receptors. Endocr Rev 16:427–442

    PubMed  CAS  Google Scholar 

  • Reubi J, Gugger M, Waser B, Schaer J (2001) Y1-mediated effect of neuro-peptide Y in cancer: breast carcinomas as targets. Cancer Res 61:4636–4641

    PubMed  CAS  Google Scholar 

  • Reubi J, Schaer J, Waser B, Wenger S, Heppeler A, Schmitt J, Maecke H (2000) Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 27:273–282

    Article  PubMed  CAS  Google Scholar 

  • Reubi JC (1995) Neuropeptide receptors in health and disease: the molecular basis for in vivo imaging. J Nucl Med 36:1825–1835

    PubMed  CAS  Google Scholar 

  • Reubi JC, Eisenwiener KP, Rink H, Waser B, Maecke H (2002) A new pep-tide somatostatin agonist with high affinity to all five somatostatin receptors. Eur J Pharmacol 456:45–49

    Article  PubMed  CAS  Google Scholar 

  • Schaer JC, Waser B, Mengod G, Reubi JC (1997) Somatostatin receptor subtypes sstl, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: comparison of mRNA analysis with receptor autoradiography. Int J Cancer 70:530–537

    Article  PubMed  CAS  Google Scholar 

  • Stolz B, Smith-Jones P, Albert R, Tolcsvai L, Briner U, Ruser G, Macke H, Weckbecker G, Bruns C (1996) Somatostatin analogs for somatostatin-receptor-mediated radiotherapy of cancer. Digestion 57[Suppl 1]: 17–21

    Article  PubMed  CAS  Google Scholar 

  • Stolz B, Weckbecker G, Smith-Jones PM, Albert R, Raulf F, Bruns C (1998) The somatostatin receptor-targeted radiotherapeutic [90Y-DPTA-DPhe1,Tyr3]octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948 tumours. Eur J Nucl Med 25:668–674

    Article  PubMed  CAS  Google Scholar 

  • Thakur ML, Kolan H, Li J, Wiaderkiewicz R, Pallela VR, Duggaraju R, Schally AV (1997) Radiolabeled somatostatin analogs in prostate cancer. Nucl Med Biod 24:105–113

    Article  CAS  Google Scholar 

  • Traub T, Petkov V, Ofluoglu S, Pangerl T, Raderer M, Fueger BJ, Schima W, Kurtaran A, Dudczak R, Virgolini I (2001) 111In-DOTA-lanreotide scintigraphy in patients with tumors of the lung. J Nucl Med 42:1309–1315

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Nuclear Medicine, Division of Radiological Chemistry, University Hospital Basel, 4031, Basel, Switzerland

    H. R. Maecke

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  1. H. R. Maecke
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Editors and Affiliations

  1. Center for Molecular Imaging Research, Building 149, Massachusetts General Hospital, 13th Street, Charleston, MA, 02129, USA

    A. A. Bogdanov Jr.

  2. Medicinal Chemistry 6, Schering AG, Müllerstr. 170-178, 13342, Berlin, Germany

    K. Licha

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Maecke, H.R. (2005). Radiolabeled Peptides in Nuclear Oncology: Influence of Peptide Structure and Labeling Strategy on Pharmacology. In: Bogdanov, A.A., Licha, K. (eds) Molecular Imaging. Ernst Schering Research Foundation Workshop, vol 49. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26809-X_3

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  • DOI: https://doi.org/10.1007/3-540-26809-X_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-21021-4

  • Online ISBN: 978-3-540-26809-3

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