21
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      68Ga-Based Radiopharmaceuticals: Production and Application Relationship

      review-article
      1 , 2
      Molecules
      MDPI
      positron emission tomography, 68Ga, chemistry, receptor targeting, peptide, GMP, dosimetry

      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

          The contribution of 68Ga to the promotion and expansion of clinical research and routine positron emission tomography (PET) for earlier better diagnostics and individualized medicine is considerable. The potential applications of 68Ga-comprising imaging agents include targeted, pre-targeted and non-targeted imaging. This review discusses the key aspects of the production of 68Ga and 68Ga-based radiopharmaceuticals in the light of the impact of regulatory requirements and endpoint pre-clinical and clinical applications.

          Related collections

          Most cited references74

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

          Processing of generator-produced 68Ga for medical application.

          The (68)Ge/(68)Ga generator provides an excellent source of positron-emitting (68)Ga. However, newly available "ionic" (68)Ge/(68)Ga radionuclide generators are not necessarily optimized for the synthesis of (68)Ga-labeled radiopharmaceuticals. The eluates have rather large volumes, a high concentration of H(+) (pH of 1), a breakthrough of (68)Ge, increasing with time or frequency of use, and impurities such as stable Zn(II) generated by the decay of (68)Ga, Ti(IV) as a constituent of the column material, and Fe(III) as a general impurity. We have developed an efficient route for the processing of generator-derived (68)Ga eluates, including the labeling and purification of biomolecules. Preconcentration and purification of the initial generator eluate are performed using a miniaturized column with organic cation-exchanger resin and hydrochloric acid/acetone eluent. The purified fraction was used for the labeling of nanomolar amounts of octreotide derivatives either in pure aqueous solution or in buffers. Using the generator post-eluate processing system, >97% of the initially eluated (68)Ga activity was obtained within 4 min as a 0.4-mL volume of a hydrochloric acid/acetone fraction. The initial amount of (68)Ge(IV) was decreased by a factor of 10(4), whereas initial amounts of Zn(II), Ti(IV), and Fe(III) were reduced by factors of 10(5), 10(2), and 10, respectively. The processed (68)Ga fraction was directly transferred to solutions containing labeling precursors-for example, DOTA-dPhe(1)-Tyr(3)-octreotide (DOTATOC) (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid). Labeling yields of >95% were achieved within 10 min. Overall yields reached 70% at 20 min after generator elution relative to the eluted (68)Ga activity, not corrected for decay. Specific activities of (68)Ga-DOTATOC were 50 MBq/nmol using a standard protocol, reaching 450 MBq/nmol under optimized conditions. Processing on a cation-exchanger in hydrochloric acid/acetone media represents an efficient strategy for the concentration and purification of generator-derived (68)Ga(III) eluates. The developed scheme guarantees high yields and safe preparation of injectable (68)Ga-labeled radiopharmaceuticals for routine application and is easy to automate. Thus, it is being successfully used in clinical environments and might contribute to a new direction for clinical PET, which could benefit significantly from the easy and safe availability of the radionuclide generator-derived metallic positron-emitter (68)Ga.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use

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

              Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development.

              The realisation that new chemical entities under development as drug candidates fail in three of four cases in clinical trials, together with increased costs and increased demands of reducing preclinical animal experiments, have promoted concepts for improvement of early screening procedures in humans. Positron emission tomography (PET) is a non-invasive imaging technology, which makes it possible to determine drug distribution and concentration in vivo in man with the drug labelled with a positron-emitting radionuclide that does not change the biochemical properties. Recently, developments in the field of rapid synthesis of organic compounds labelled with positron-emitting radionuclides have allowed a substantial number of new drug candidates to be labelled and potentially used as probes in PET studies. Together, these factors led to the logical conclusion that early PET studies, performed with very low drug doses-PET-microdosing-could be included in the drug development process as one means for selection or rejection of compounds based on performance in vivo in man. Another important option of PET, to evaluate drug interaction with a target, utilising a PET tracer specific for this target, necessitates a more rapid development of such PET methodology and validations in humans. Since only very low amounts of drugs are used in PET-microdosing studies, the safety requirements should be reduced relative to the safety requirements needed for therapeutic doses. In the following, a methodological scrutinising of the concept is presented. A complete pre-clinical package including limited toxicity assessment is proposed as a base for the regulatory framework of the PET-microdosing concept.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                16 July 2015
                July 2015
                : 20
                : 7
                : 12913-12943
                Affiliations
                [1 ]Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala SE-751 85, Sweden; E-Mail: irina.velikyan@ 123456akademiska.se ; Tel.: +46-0-70-483-4137; Fax: +46-0-18-611-0619
                [2 ]PET Center, Center for Medical Imaging, Uppsala University Hospital, Uppsala SE-751 85, Sweden
                Article
                molecules-20-12913
                10.3390/molecules200712913
                6332429
                26193247
                88ca03e9-e086-4537-be7f-334db4d90134
                © 2015 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 license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 June 2015
                : 06 July 2015
                Categories
                Review

                positron emission tomography,68ga,chemistry,receptor targeting,peptide,gmp,dosimetry

                Comments

                Comment on this article