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, (47)Sc and (44)Sc, are perspective radioisotopes for radiotherapy and diagnostic imaging. (47)Sc decays with a half-life of 3.35 days and a maximum β(-) energy of 600 keV and could be an alternative to carrier added (177)Lu radionuclide for targeted radionuclide therapy. Another scandium radionuclide (44)Sc (t(1/2) = 3.92 h) is an ideal β(+) emitter for PET diagnosis. It can be obtained as a daughter of the long-lived (44)Ti (t(1/2) = 60.4 y) from (44)Ti/(44)Sc generator. For complexation of scandium radionuclides macrocyclic ligands having a cavity size similar to Sc(3+) 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 (44)Sc and (47)Sc to biomolecules. The determined stability constant of Sc-DOTA complex logK = 27.0 is comparable with stability constants for Y(3+) and heaviest lanthanides but is higher than those for In(3+) and Ga(3+). Also (46)Sc-DOTATATE conjugate exhibits high stability in-vitro studies. The (13)C 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.