In vitro and in vivo characterization of ⁶⁷Ga³⁺ complexes with cis, cis-1, 3, 5-triamino-cyclohexane-N, N′, N″-triacetic acid derivatives

The aim of this study was to investigate the in vitro and in vivo performance of a ⁶⁷Ga complex with cis, cis-1, 3, 5-triaminocyclohexane-N, N′, N″-triacetic acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity, acid stability, human serum stability and biodistribution in mice of ⁶⁷Ga(tachta) were investigated. The ⁶⁷Ga(tachta) complex forms at 10^-3 M tachta concentration at 40°C in 100% yield; it is neutral, non-lipophilic, 90% stable at pH = 4 and 5 and 100% stable at pH = 6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr ⁶⁷Ga(tachta) exists in serum as a free complex. At 24 hr, 30% of ⁶⁷Ga(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that ⁶⁷Ga(tachta) rapidly clears via the kidneys from the body with less than 10% of injected activity left in the body at 3 hours and only 6% remaining after 24 hr. The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1.15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, ⁶⁷Ga(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET.