In vitro and in vivo characterization of Ga-67(3+) 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 performan ce of a Ga-67 complex with cis,cis-1,3,5-triaminocyclohexane-N,N,N"-triacet ic acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceut ical for PET imaging. The radiolabeling procedure, electrophoretic properti es. lipophilicity. acid stability, human serum stability and biodistributio n in mice of Ga-67(tachta) were investigated. The Ga-67(tachta) complex for ms at 10(-3) M tachta concentration at 40 degreesC in 100% yield; it is neu tral, 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 Ga -67(tachta) exists in serum as a free complex. At 24 hr, 30% of Ga-67(tacht a) is reversibly bound to transferrin-albumin fraction of serum, and that t his percentage remains unchanged for a period of 4 d. Biodistribution in mi ce showed that Ga-67(tachta) rapidly clears via the kidneys from the body w ith 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 h r accumulation, in comparison with the 3 hr time point. Based upon these da ta, Ga-67(tachta) may be considered as a candidate for developing new Ga(II I) radiopharmaceuticals for PET, (C) 2001 Elsevier Science Inc. All rights reserved.