11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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 68Ga 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 [ 68Ga]Ga- 8 and [ 68Ga]Ga- 9 were studied. Both 8 and 9 readily form 68Ga-complexes stable to ten-fold dilution with saline. However, in fetal bovine serum, only [ 68Ga]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 [ 68Ga]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 [ 68Ga]Ga- 9 in the pathology site was higher than that in animals with bone pathology. Moreover, the accumulation of [ 68Ga]Ga- 9 in inflammation sites was more stable than that for [ 68Ga]Ga-citrate. The percentage of [ 68Ga]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 [ 68Ga]Ga-citrate.

          Related collections

          Most cited references44

          • Record: found
          • Abstract: found
          • Article: not found

          Matching chelators to radiometals for radiopharmaceuticals.

          Radiometals comprise many useful radioactive isotopes of various metallic elements. When properly harnessed, these have valuable emission properties that can be used for diagnostic imaging techniques, such as single photon emission computed tomography (SPECT, e.g.(67)Ga, (99m)Tc, (111)In, (177)Lu) and positron emission tomography (PET, e.g.(68)Ga, (64)Cu, (44)Sc, (86)Y, (89)Zr), as well as therapeutic applications (e.g.(47)Sc, (114m)In, (177)Lu, (90)Y, (212/213)Bi, (212)Pb, (225)Ac, (186/188)Re). A fundamental critical component of a radiometal-based radiopharmaceutical is the chelator, the ligand system that binds the radiometal ion in a tight stable coordination complex so that it can be properly directed to a desirable molecular target in vivo. This article is a guide for selecting the optimal match between chelator and radiometal for use in these systems. The article briefly introduces a selection of relevant and high impact radiometals, and their potential utility to the fields of radiochemistry, nuclear medicine, and molecular imaging. A description of radiometal-based radiopharmaceuticals is provided, and several key design considerations are discussed. The experimental methods by which chelators are assessed for their suitability with a variety of radiometal ions is explained, and a large selection of the most common and most promising chelators are evaluated and discussed for their potential use with a variety of radiometals. Comprehensive tables have been assembled to provide a convenient and accessible overview of the field of radiometal chelating agents.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Prospective of 68Ga-Radiopharmaceutical Development

            Positron Emission Tomography (PET) experienced accelerated development and has become an established method for medical research and clinical routine diagnostics on patient individualized basis. Development and availability of new radiopharmaceuticals specific for particular diseases is one of the driving forces of the expansion of clinical PET. The future development of the 68Ga-radiopharmaceuticals must be put in the context of several aspects such as role of PET in nuclear medicine, unmet medical needs, identification of new biomarkers, targets and corresponding ligands, production and availability of 68Ga, automation of the radiopharmaceutical production, progress of positron emission tomography technologies and image analysis methodologies for improved quantitation accuracy, PET radiopharmaceutical regulations as well as advances in radiopharmaceutical chemistry. The review presents the prospects of the 68Ga-based radiopharmaceutical development on the basis of the current status of these aspects as well as wide range and variety of imaging agents.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Critical evaluation of stability constants of phosphonic acids (IUPAC Technical Report)

              Available experimental data on stability constants of proton and metal complexes for 10 phosphonic acids [methylphosphonic acid, 1-hydroxyethane-1,1-diylbisphosphonic acid, dichloromethylenebisphosphonic acid, amino-methanephosphonic acid,
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                18 April 2021
                April 2021
                : 26
                : 8
                : 2357
                Affiliations
                [1 ]Department of Radiation Medical Technologies, State Research Center—Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str. 46, 123182 Moscow, Russia; amaruk@ 123456list.ru (A.Y.M.); mitrofanoff.yura@ 123456yandex.ru (I.A.M.); mr.alekslunev@ 123456gmail.com (A.S.L.); christfmbc@ 123456gmail.com (K.A.L.); klementyeva.olga@ 123456gmail.com (O.E.K.); gkodina@ 123456yandex.ru (G.E.K.)
                [2 ]Laboratory of Organophosphorus Сompounds, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severnyi proezd 1, 142432 Chernogolovka, Russia; rvalery@ 123456dio.ru (V.V.R.); mager1988@ 123456gmail.com (V.E.B.)
                [3 ]Laborotary of Novel Physicochemical Problems, Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskii pr. 31/4, 119071 Moscow, Russia; solovev-vp@ 123456mail.ru (V.P.S.); tsiv@ 123456phyche.ac.ru (A.Y.T.)
                Author notes
                [* ]Correspondence: tsebrikova@ 123456yandex.ru
                Author information
                https://orcid.org/0000-0003-2576-2338
                https://orcid.org/0000-0002-3967-1034
                https://orcid.org/0000-0001-5249-8507
                https://orcid.org/0000-0002-1215-4256
                https://orcid.org/0000-0002-2590-5098
                Article
                molecules-26-02357
                10.3390/molecules26082357
                8073962
                4d061621-1e3d-44f1-b827-82c030bf5db9
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 28 February 2021
                : 16 April 2021
                Categories
                Article

                68ga,diphosphonate,aminodiphosphonic acid,stability constant,radiopharmaceutical,bone-seeking,inflammation,68ga-citrate

                Comments

                Comment on this article