Evaluation of Applicability of Aminodiphosphonic Acids for the Development of Bone-Seeking 68Ga-Radiopharmaceuticals

Synthesis, Complexation Properties, and Evaluation of New Aminodiphosphonic Acids as Vector Molecules for 68Ga Radiopharmaceuticals

“…This correlation becomes less significant with increasing ligand concentration and becomes statistically insignificant (p > 0.05) at 5 mM of 9. In addition to the results [14], we carried out similar experiments with [ 68 Ga]Ga-1 and found no statistically significant correlation even at a concentration of 1 in the reaction mixture being as low as 0.2 mM. Thus, there are three patterns of acetate concentration influencing the labelling reaction yield.…”

“…In Table 3, the biodistribution data of [ 68 Ga]Ga-9 and [ 68 Ga]Ga-acetate in animals with fractures are presented. Non-target biodistribution pathways and bone pathology uptake for [ 68 Ga]Ga-9 are comparable to those of [ 68 Ga]Ga-1 and [ 68 Ga]Ga-2 [14]. The pathology site/intact bone ratio for [ 68 Ga]Ga-9 is inferior to that of [ 68 Ga]Ga-oxa-bis-ethylenenitrile tetra(methylene phosphonic acid) (3) [33] and even to that of [ 68 Ga]Ga-acetate studied in this experiment (Table 3).…”

“…Thus, there are three patterns of acetate concentration influencing the labelling reaction yield. The influence of the buffering agent type on the labelling reaction yield was analysed before for [ 68 Ga]Ga-1 [14]. The influence of acetate concentration on the labelling reaction yield was demonstrated for DOTA-conjugated molecules [27].…”

“…Radiolabelling and evaluation of [ 68 Ga]Ga-8 and [ 68 Ga]Ga-9 stability were carried out in triplicate using procedures similar to those described in Reference [14]. In short, for labelling with 68 Ga sodium acetate (buffering agent) solutions of various concentrations, (0.1, 0.5, or 1 M) and 68 Ge/ 68 Ga generator eluate were added to the Eppendorf tubes containing 0.1-20 µmol of 8 or 9. pH of the mixtures was then adjusted using NaOH and HCl of pre-estimated concentrations.…”

“…Besides, they can be easily prepared by the addition of two phosphorous acid molecules to a nitrile group. Recently, we studied two 68 Ga complexes with organic ligands containing aminodiphosphonic groups (1,7-diamino-4-oxaheptane-1,1,7,7-tetraphosphonic (1, Figure 1) and 1,7-diamino-4-hydroxycarbonylheptane-1,1,7,7-tetraphosphonic acids (2, Figure 1)) as potential bone-seeking agents [14,15]. Compounds 1 and 2 are closely related to the oxa-bysethylenenitrile tetra(methylene phosphonic acid) (3, Figure 1), which is a component of the widely used in Russia [ 153 Sm]samarium oxabifore therapeutic radiopharmaceutical [16].…”