| Autor: |
Maruk AY; Department of Radiation Medical Technologies, State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str. 46, 123182 Moscow, Russia., Ragulin VV; Laboratory of Organophosphorus Сompounds, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severnyi proezd 1, 142432 Chernogolovka, Russia., Mitrofanov IA; Department of Radiation Medical Technologies, State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str. 46, 123182 Moscow, Russia., Tsebrikova GS; Laborotary of Novel Physicochemical Problems, Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskii pr. 31/4, 119071 Moscow, Russia., Solov'ev VP; Laborotary of Novel Physicochemical Problems, Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskii pr. 31/4, 119071 Moscow, Russia., Lunev AS; Department of Radiation Medical Technologies, State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str. 46, 123182 Moscow, Russia., Lunyova KA; Department of Radiation Medical Technologies, State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str. 46, 123182 Moscow, Russia., Klementyeva OE; Department of Radiation Medical Technologies, State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str. 46, 123182 Moscow, Russia., Baulin VE; Laboratory of Organophosphorus Сompounds, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severnyi proezd 1, 142432 Chernogolovka, Russia., Kodina GE; Department of Radiation Medical Technologies, State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str. 46, 123182 Moscow, Russia., Tsivadse AY; Laborotary of Novel Physicochemical Problems, Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskii pr. 31/4, 119071 Moscow, Russia. |
| Abstrakt: |
Two new aminodiphosphonic acids derived from salicylic acid and its phosphonic analogue were prepared through a simple and efficient synthesis. 2-[(2-Amino-2,2-diphosphono)ethyloxy]-benzoic acid 8 and 2-[(2-amino-2,2-diphosphono)ethyloxy]-5-ethyl-phenylphosphonic acid 9 were evaluated for their applicability as 68 Ga binding bone-seeking agents. Protonation constants of 8 and 9 and stability constants of the Ga 3+ complexes with 8 and 9 in water were determined. The stability constant of Ga 3+ complex with fully phosphorylated acid 9 (log K GaL = 31.92 ± 0.32) significantly exceeds stability constant of Ga 3+ complex with 8 (log K GaL = 26.63 ± 0.24). Ligands 8 and 9 are as effective for Ga 3+ cation binding as ethylenediamine- N , N' -diacetic- N , N' -bis(methy1enephosphonic) acid and ethylenediamine- N , N , N' , N' -tetrakis(methylenephosphonic) acid, respectively. The labelling process and stability of [ 68 Ga]Ga- 8 and [ 68 Ga]Ga- 9 were studied. Both 8 and 9 readily form 68 Ga-complexes stable to ten-fold dilution with saline. However, in fetal bovine serum, only [ 68 Ga]Ga- 9 was stable enough to be subject to biological evaluation. It was injected into rats with bone pathology and aseptic inflammation of soft tissues. For [ 68 Ga]Ga- 9 in animals with a bone pathology model in 60 and 120 min after injection, a slight accumulation in the pathology site, stable blood percentage level, and moderate accumulation in the liver were observed. For animals with an aseptic inflammation, the accumulation of [ 68 Ga]Ga- 9 in the pathology site was higher than that in animals with bone pathology. Moreover, the accumulation of [ 68 Ga]Ga- 9 in inflammation sites was more stable than that for [ 68 Ga]Ga-citrate. The percentage of [ 68 Ga]Ga- 9 in the blood decreased from 3.1% ID/g (60 min) to 1.5% ID/g (120 min). Accumulation in the liver was comparable to that obtained for [ 68 Ga]Ga-citrate. |
