In vitro and in vivo characterization of 67Ga(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 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 degrees 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.
Dadachova
E
E
Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Park
C
C
Eberly
N
N
Ma
D
D
Paik
C H
CH
Brechbiel
M W
MW
D000818:Animals; D003510:Cyclohexanes / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004355:Drug Stability; D005260:Female; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D003510:Cyclohexanes; D005710:Gallium Radioisotopes; C421107:H3tachta; D019275:Radiopharmaceuticals