Macrocyclic complexes of scandium radionuclides as precursors for diagnostic and therapeutic radiopharmaceuticals

The aim of this study was to evaluate new ligands which can be applied for labeling biomolecules with scandium radionuclides. Two radionuclides of scandium, Sc-47 and Sc-44, are perspective radioisotopes for radiotherapy and diagnostic imaging. Sc-47 decays with a half-life of 3.35 days and a maximum beta(-) energy of 600 keV and could be an alternative to carrier added Lu-177 radionuclide for targeted radionuclide therapy. Another scandium radionuclide Sc-44 (t(1/2) = 3.92 h) is an ideal beta(+) emitter for PET diagnosis. It can be obtained as a daughter of the long-lived Ti-44 (t(1/2) = 60.4 y) from Ti-44/Sc-44 generator. For complexation of scandium radionuclides macrocyclic ligands having a cavity size similar to Sc3+ ionic radius were selected: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7 triacetic acid (NOTA), 1,4,7-triazacyclodecane-1,4,7 triacetic acid and 1,4,7-triazacycloundecane triacetic acid, and analogs of NOTA with 10, 11 and 12 atoms of the carbon in the ring. Our results have shown that from the studied macrocyclic ligands studied DOTA is most efficient for binding scandium radionuclides Sc-44 and Sc-47 to biomolecules. The determined stability constant of Sc-DOTA complex logK = 27.0 is comparable with stability constants for Y3+ and heaviest lanthanides but is higher than those for In3+ and Ga3+. Also Sc-46-DOTATATE conjugate exhibits high stability in-vitro studies. The C-13 NMR studies have shown that Sc-DOTA like Lu-DOTA forms in solution complexes with eight-coordination geometry. The lipophilicity of Sc-DOTATATE is nearly identical to that of Lu-DOTATATE, which suggests similar receptor affinity of both radioconjugates. (C) 2010 Elsevier Inc. All rights reserved.