Mild and efficient 64Cu labeling of perhydro-1, 4-diazepine derivatives for potential use with large peptides, proteins and antibodies

Lukas Greifenstein 1 , Denise Späth 1 , Jean Phillip Sinnes 1 , Tilmann Grus 1 ,  and Frank Rösch 1
  • 1 Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Straßmann-Weg 2, 55128 Mainz, Germany
Lukas Greifenstein
  • Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Straßmann-Weg 2, 55128 Mainz, Germany
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, Denise Späth
  • Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Straßmann-Weg 2, 55128 Mainz, Germany
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, Jean Phillip Sinnes
  • Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Straßmann-Weg 2, 55128 Mainz, Germany
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, Tilmann Grus
  • Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Straßmann-Weg 2, 55128 Mainz, Germany
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and Frank Rösch
  • Corresponding author
  • Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Straßmann-Weg 2, 55128 Mainz, Germany
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Abstract

DATA (6-Amino-1,4-diazapine-triacetate) and AAZTA (6-Amino-1,4-diazapine-tetracetate) chelators represent a novel approach representing hybrid-chelates: possessing significant cyclic and acyclic character. It is believed that flexibility of the acyclic part facilitates rapid complexation, whilst the preorganized cyclic part minimizes the energy barrier to complexation and inhibits decomplexation processes. So far, these chelators have been used exclusively with 44Sc and 68Ga only. Recent results with natCu predict high stabilities for Cu-AAZTA, yet no radioactive labeling of AAZTA or DATA with 64Cu or any additional radioactive isotope has been reported. We present the one pot synthesis of the bifunctional derivatives AAZTA5OMe and DATA5mOMe and their labeling with 64Cu. In addition, in vitro stability of the respective complexes are presented.

  • 1.

    Anderson, C. J., Ferdani, R.: Copper-64 radiopharmaceuticals for PET imaging of cancer: advances in preclinical and clinical research. Cancer Biother. Radiopharm. 24, 379 (2009).

    • Crossref
    • PubMed
    • Export Citation
  • 2.

    Niccoli Asabella, A., Cascini, G. L., Altini, C., Paparella, D., Notaristefano, A., Rubini, G.: The copper radioisotopes: a systematic review with special interest to 64Cu. Biomed. Res. Int. 2014, 786463 (2014).

    • PubMed
    • Export Citation
  • 3.

    Shokeen, M., Anderson, C. J.: Molecular imaging of cancer with copper-64 radiopharmaceuticals and positron emission tomography (PET). Acc. Chem. Res. 42, 832 (2009).

    • Crossref
    • PubMed
    • Export Citation
  • 4.

    Wu, N., Kang, C. S., Sin, I., Ren, S., Liu, D., Ruthengael, V. C., Lewis, M. R., Chong, H.-S.: Promising bifunctional chelators for copper 64-PET imaging: practical 64Cu radiolabeling and high in vitro and in vivo complex stability. J. Biol. Chem. 21, 177 (2015).

  • 5.

    Kumar, A., Hao, G., Liu, L., Ramezani, S., Hsieh, J.-T., Öz, O. K., Sun, X.: Click-chemistry strategy for labeling antibodies with copper-64 via a cross-bridged tetraazamacrocyclic chelator scaffold. Bioconj. Chem. 26, 782 (2015).

    • Crossref
    • Export Citation
  • 6.

    Banerjee, S. R., Pullambhatla, M., Foss, C. A., Nimmagadda, S., Ferdani, R., Anderson, C. J., Mease, R. C., Pomper, M. G.: 64Cu-labeled inhibitors of prostate-specific membrane antigen for PET imaging of prostate cancer. J. Med. Chem. 57, 2657 (2014).

    • Crossref
    • Export Citation
  • 7.

    Novak-Hofer, I., Schubiger, P. A.: Copper-67 as a therapeutic nuclide for radioimmunotherapy. EJNMMI 29, 821 (2002).

  • 8.

    Smith, N. A., Bowers, D. L., Ehst, D. A.: The production, separation, and use of 67Cu for radioimmunotherapy: a review. Appl. Radiat. Isot. 70, 2377 (2012).

    • Crossref
    • PubMed
    • Export Citation
  • 9.

    Ahmedova, A., Todorov, B., Burdzhiev, N., Goze, C.: Copper radiopharmaceuticals for theranostic applications. Eur. J. Med. Chem. 157, 1406 (2018).

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Conry, R. R.: Copper: inorganic & coordination chemistry based in part on the article copper: inorganic & coordination chemistry by Rebecca R. Conry & Kenneth D. Karlin which appeared in the encyclopedia of inorganic chemistry, First Edition. In: R. B. King, R. H. Crabtree, C. M. Lukehart, D. A. Atwood, R. A. Scott (Eds.), Encyclopedia of Inorganic Chemistry (2006), John Wiley & Sons, Ltd, Chichester, UK, p. 2309.

  • 11.

    Wadas, T. J., Wong, E. H., Weisman, G. R., Anderson, C. J.: Copper chelation chemistry and its role in copper radiopharmaceuticals. Curr. Pharm. Res. 13, 3 (2007).

    • Crossref
    • Export Citation
  • 12.

    Nurchi, V. M., Crisponi, G., Crespo-Alonso, M., Lachowicz, J. I., Szewczuk, Z., Cooper, G. J. S.: Complex formation equilibria of Cu(II) and Zn(II) with triethylenetetramine and its mono- and di-acetyl metabolites. Dalton Trans. 42, 6161 (2013).

    • Crossref
    • PubMed
    • Export Citation
  • 13.

    Wadas, T. J., Wong, E. H., Weisman, G. R., Anderson, C. J.: Coordinating radiometals of copper, gallium, indium, yttrium, and zirconium for PET and SPECT imaging of disease. Chem. Rev. 110, 2858 (2010).

    • Crossref
    • PubMed
    • Export Citation
  • 14.

    Cai, Z., Anderson, C. J.: Chelators for copper radionuclides in positron emission tomography radiopharmaceuticals. J. Labed. Compd. Radiopharm. 57, 224 (2013).

  • 15.

    Aime, S., Calabi, L., Cavallotti, C., Gianolio, E., Giovenzana, G. B., Losi, P., Maiocchi, A., Palmisano, G., Sisti, M.: Gd-AAZTA: a new structural entry for an improved generation of MRI contrast agents. Inorg. Chem. 43, 7588 (2004).

    • Crossref
    • PubMed
    • Export Citation
  • 16.

    Sengar, R. S., Nigam, A., Geib, S. J., Wiener, E. C.: Syntheses and crystal structures of gadolinium and europium complexes of AAZTA analogues. Polyhedron. 28, 1525 (2009).

    • Crossref
    • Export Citation
  • 17.

    Baranyai, Z., Uggeri, F., Maiocchi, A., Giovenzana, G. B., Cavallotti, C., Takács, A., Tóth, I., Bányai, I., Bényei, A., Brucher, E., Aime, S.: Equilibrium, kinetic and structural studies of AAZTA complexes with Ga3+ In3+ and Cu2+. Eur. J. Inorg. Chem. 2013, 147 (2013).

    • Crossref
    • Export Citation
  • 18.

    Tei, L., Gugliotta, G., Fekete, M., Kálmán, F. K., Botta, M.: Mn(II) complexes of novel hexadentate AAZTA-like chelators: a solution thermodynamics and relaxometric study. Dalton Trans. 40, 2025 (2011).

    • Crossref
    • PubMed
    • Export Citation
  • 19.

    Vágner, A., D’Alessandria, C., Gambino, G., Schwaiger, M., Aime, S., Maiocchi, A., Tóth, I., Baranyai, Z., Tei, L.: A rigidified AAZTA-like ligand as efficient chelator for 68Ga radiopharmaceuticals. Chemistry Select. 1, 163 (2016).

  • 20.

    Farkas, E., Nagel, J., Waldron, B. P., Parker, D., Tóth, I., Brücher, E., Rösch, F., Baranyai, Z.: Equilibrium, kinetic and structural properties of gallium(III) and some divalent metal complexes formed with the new DATAm and DATA5m ligands. Chemistry 23, 10358 (2017).

    • Crossref
    • PubMed
    • Export Citation
  • 21.

    Nagy, G., Szikra, D., Trencsényi, G., Fekete, A., Garai, I., Giani, A. M., Negri, R., Masciocchi, N., Maiocchi, A., Uggeri, F., Tóth, I., Aime, S., Giovenzana, G. B., Baranyai, Z.: AAZTA: An ideal chelating agent for the development of 44 Sc PET imaging agents. Angew. Chem. 129, 2150 (2017).

    • Crossref
    • Export Citation
  • 22.

    Seemann, J., Waldron, B., Parker, D., Roesch, F.: DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature. EJNMMI Radiopharm. Chem. 1, 4 (2016).

    • PubMed
    • Export Citation
  • 23.

    Nock, B. A., Kaloudi, A., Nagel, J., Sinnes, J.-P., Roesch, F., Maina, T.: Novel bifunctional DATA chelator for quick access to site-directed PET 68Ga-radiotracers: preclinical proof-of- principle with Tyr3octreotide. Dalton Trans. 46, 14584–14590 (2017).

    • Crossref
    • Export Citation
  • 24.

    Bass, L. A., Wang, M., Welch, M. J., Anderson, C. J.: In vivo transchelation of copper-64 from TETA-octreotide to superoxide dismutase in rat liver. Bioconj. Chem. 11, 527 (2000).

    • Crossref
    • Export Citation
  • 25.

    Moi, M. K., Meares, C. F., McCall, M. J., Cole, W. C., DeNardo, S. J.: Copper chelates as probes of biological systems: Stable copper complexes with a macrocyclic bifunctional chelating agent. Anal. Biochem. 148, 249 (1985).

    • Crossref
    • PubMed
    • Export Citation
  • 26.

    McQuade, P., Miao, Y., Yoo, J., Quinn, T. P., Welch, M. J., Lewis, J. S.: Imaging of melanoma using 64Cu- and 86Y-DOTA-ReCCMSH(Arg11), a cyclized peptide analogue of alpha-MSH. J. Med. Chem. 48, 2985 (2005).

    • Crossref
    • PubMed
    • Export Citation
  • 27.

    Chen, X., Hou, Y., Tohme, M., Park, R., Khankaldyyan, V., Gonzales-Gomez, I., Bading, J. R., Laug, W. E., Conti, P. S.: Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor alphavbeta3-integrin expression. J. Nucl. Med. 45, 1776 (2004).

    • PubMed
    • Export Citation
  • 28.

    Anderson, C. J., Jones, L. A., Bass, L. A., Sherman, E. L., McCarthy, D. W., Cutler, P. D., Lanahan, M. V., Cristel, M. E., Lewis, J. S., Schwarz, S. W.: Radiotherapy, toxicity and dosimetry of copper-64-TETA-octreotide in tumor-bearing rats. J. Nucl. Med. 39, 1944 (1998).

    • PubMed
    • Export Citation
  • 29.

    Chen, X., Park, R., Tohme, M., Shahinian, A. H., Bading, J. R., Conti, P. S.: MicroPET and autoradiographic imaging of breast cancer alpha v-integrin expression using 18F- and 64Cu-labeled RGD peptide. Bioconj. Chem. 15, 41 (2004).

    • Crossref
    • Export Citation
  • 30.

    Chen, X., Sievers, E., Hou, Y., Park, R., Tohme, M., Bart, R., Bremner, R., Bading, J. R., Conti, P. S.: Integrin αvβ3-targeted imaging of lung cancer. Neoplasia 7, 271 (2005).

    • Crossref
    • Export Citation
  • 31.

    Anderson, C. J., Dehdashti, F., Cutler, P. D., Schwarz, S. W., Laforest, R., Bass, L. A., Lewis, J. S., McCarthy, D. W.: 64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors. J. Nucl. Med. 42, 213 (2001).

    • PubMed
    • Export Citation
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Radiochimica Acta publishes original papers, review articles, and “rapid communications” (short articles of a more timely interest) on all chemical aspects of nuclear science and technology. The journal is geared toward scientists who are actively engaged in research work.

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