Synthesis of Auger Electron-Emitting Radiopharmaceuticals

Abstract

Targeted radiotherapy using Auger electron-emitting pharmaceuticals offers both advantages and challenges compared to alternative alpha - or beta -emitting agents. The low energy Auger electrons deposit their energy within the target cell thereby minimizing collateral damage. To achieve this effect, however, the radiopharmaceutical must incorporate the appropriate radionuclide, be efficiently synthesized, and once administered, be distributed selectively to its biological target. This review covers the synthesis of agents which have prepared over the past decade either as Auger electron-emitting radiopharmaceuticals or which have the potential as such. While not an exhaustive review, the major classes of agents, such as hormone receptor ligands, nucleoside analogs and intercalating agents are described.

Nucleoside-metallacarborane conjugates - synthesis of a uridine - bearing 3,3,3-(CO)3-closo-3,1,2-ReC2B9H10 complex

“…The applications of these compounds include the imaging of specific mRNAs, i.e., the visualisation of the expression of defined genes in vivo; the monitoring of antisense chemotherapy; gene therapy, i.e., the targeting of radiation damage to specific DNA sequences to destroy tumours; the imaging of protein targets using aptamer oligonucleotides; and pre-targeting based on hybridisation with the complementary sequence. [22][23][24] Often, radiolabeling can be achieved with complexes of radioactive metal isotopes. Encouraging results have been reported using chromium-51, gallium-57 and -68, indium-111, platinum-193 or technetium-99 attached to nucleic acids, usually in the form of complexes with a suitable chelating ligand.…”

Synthesis and Characterization of Iodinated Tetrahydroquinolines Targeting the G Protein-Coupled Estrogen Receptor GPR30

“…The development of radiolabeled 17α-iodovinylestradiols has progressed to clinical assessment of 123 I-labeled 11β-methoxy-iodovinylestradiol for estrogen receptor imaging in breast cancer 36. Radiolabeled analogs incorporating Auger-emitting isotopes 125 I and 123 I have potential as therapeutic agents for estrogen receptor expressing tumors 30,37. The high specific activity and sensitivity of detection possible using the γ-emitting isotope 125 I offers practical advantages for receptor binding studies in the laboratory, and allows efficient determination of receptor content in tissues and convenient detection and quantification of images.…”

“…The commercial availability of [ 3 H]-17β-estradiol has facilitated the characterization of receptor distribution and ligand binding of the classical estrogen receptors using cellular extracts, cell culture, and in vivo models. The development of estrogen receptor ligands radiolabeled with positron- or γ-emitting halogen isotopes for PET and SPECT imaging applications, as well as potential therapeutic applications based on estrogen receptor targeting, has been intensively studied over the past 30 years. − Clinical oncologists have successfully used [ 18 F]FES for staging and visualizing primary and metastatic carcinomas. , The quantification of ERα and ERβ levels affords predictive value for determining outcomes of hormone therapy in breast cancer. , The development of radiolabeled 17α-iodovinylestradiols has progressed to clinical assessment of 123 I-labeled 11β-methoxyiodovinylestradiol for estrogen receptor imaging in breast cancer . Radiolabeled analogues incorporating Auger-emitting isotopes 125 I and 123 I have potential as therapeutic agents for estrogen receptor expressing tumors. , The high specific activity and sensitivity of detection possible using the γ-emitting isotope 125 I offer practical advantages for receptor binding studies in the laboratory and allow efficient determination of receptor content in tissues and convenient detection and quantification of images.…”

“…The development of estrogen receptor ligands radiolabeled with positron-or γ-emitting halogen isotopes for PET and SPECT imaging applications, as well as potential therapeutic applications based on estrogen receptor targeting, has been intensively studied over the past 30 years. [27][28][29][30][31] Clinical oncologists have successfully used [ 18 F]FES for staging and visualizing primary and metastatic carcinomas. 32,33 The quantification of ERR and ERβ levels affords predictive value for determining outcomes of hormone therapy in breast cancer.…”

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“…Recent developments in these areas are reported in a number of useful reviews of the field of bio-inorganic pharmaceuticals in general [2][3][4] and of radionuclide imaging 5 (especially using anti-sense probes 6,7 ) and therapy. [8][9][10][11]…”