Development and evaluation of the new ligand NOTET for the complexation of <sup>68</sup>Ga — ASN Events
  1. Schedule
  2. Conference Breakfast: Moderated Poster Walk - Novel Theranostics
  3. Development and evaluation of the new ligand NOTET for the complexation of 68Ga

Development and evaluation of the new ligand NOTET for the complexation of 68Ga (#110)

Leena Hogan 1 2 , Trevor Hambley 1 , Peter Turner 1 , Vu Nguyen 2 , Ivan Greguric 2 , Benjamin Fraser 2 , Nigel Lengkeek 2
  1. School of Chemistry, University of Sydney, Sydney, NSW, Australia
  2. Radioisotopes and Radiotracers, ANSTO, Lucas Heights, NSW, Australia

Clinical and research interest in metallic radioisotopes (radiometals) for use in molecular imaging, continues to grow. Currently there is tremendous interest in the β+ emitter Gallium-68 (68Ga) due to its excellent decay profile (97% positron emission) and ease of use, via 68Ge/68Ga generators.  The development of new ligands for the complexation of 68Ga is key to developing the field. We believe improvements can be made in a number of areas including in-vivo stability of metal complexes, tempering radiolabelling conditions for sensitive bioconjugates, and decreasing radiation doses to vital organs such the kidneys and bone marrow by attenuating pharmacokinetics of the complexes.

We have developed an isosteric analogue of the well-established polyamino-polycarboxylate ligand, NOTA, a ligand we have termed NOTET (1), in order to modify properties such as size and lipophillicity. We have undertaken an extensive assessment of the properties of the two ligands, NOTA and NOTET, by means of comparison of radiolabeling conditions, in-vitro stability, in-vivo imaging and bio-distribution. As well as this we have compared various synthetic routes to produce NOTET and studied a variety of ‘cold’ metal complexes of the ligand.

577f37a65492b-notet.bmp

  1. F. Touti, A. K. Singh, P. Maurin, L. Canaple, O. Beuf, J. Samarut, J. Hasserodt, J. Med. Chem. 2011, 54, 4274
  2. F. Touti, F. Avenier, Q. Lefebvre, P. Maurin, J. Hasserodt, Euro. J. Org. Chem. 2010, 1928
  3. L. Tei, G. Baum, A. J. Blake, D. Fenske, M. Schroder, J. Chem. Soc., Dalton Trans. 2000, 2793W
  4. G. Finnegan, R. A. Henry, R. Lofquist, J. Am. Chem. Soc., 1958, 80 (15), 3908
  5. Z. P. Demko, K. B. Sharpless, J. Org. Chem. 2001, 66, 7945
  6. R. J. Herr, Bioorg. Med. Chem. 2002, 10, 3379
  7. E. Boros, C. L. Ferreira, J. F. Cawthray, E. W. Price, B. O. Patrick, D. W. Wester, M. J. Adam, C. Orvig, J. Am. Chem. Soc. 2010, 132, 15726