A practical guide to the construction of radiometallated bioconjugates for positron emission tomography

Dalton Trans. 2011 Jun 21;40(23):6168-95. doi: 10.1039/c0dt01595d. Epub 2011 Mar 25.

Abstract

Positron emission tomography (PET) has become a vital imaging modality in the diagnosis and treatment of disease, most notably cancer. A wide array of small molecule PET radiotracers have been developed that employ the short half-life radionuclides (11)C, (13)N, (15)O, and (18)F. However, PET radiopharmaceuticals based on biomolecular targeting vectors have been the subject of dramatically increased research in both the laboratory and the clinic. Typically based on antibodies, oligopeptides, or oligonucleotides, these tracers have longer biological half-lives than their small molecule counterparts and thus require labeling with radionuclides with longer, complementary radioactive half-lives, such as the metallic isotopes (64)Cu, (68)Ga, (86)Y, and (89)Zr. Each bioconjugate radiopharmaceutical has four component parts: biomolecular vector, radiometal, chelator, and covalent link between chelator and biomolecule. With the exception of the radiometal, a tremendous variety of choices exists for each of these pieces, and a plethora of different chelation, conjugation, and radiometallation strategies have been utilized to create agents ranging from (68)Ga-labeled pentapeptides to (89)Zr-labeled monoclonal antibodies. Herein, the authors present a practical guide to the construction of radiometal-based PET bioconjugates, in which the design choices and synthetic details of a wide range of biomolecular tracers from the literature are collected in a single reference. In assembling this information, the authors hope both to illuminate the diverse methods employed in the synthesis of these agents and also to create a useful reference for molecular imaging researchers both experienced and new to the field.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies / chemistry
  • Antibodies / immunology
  • Chelating Agents / chemistry
  • Coordination Complexes / chemistry
  • Humans
  • Isotope Labeling
  • Metals / chemistry*
  • Neoplasms / diagnostic imaging
  • Oligonucleotides / chemistry
  • Oligopeptides / chemistry
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemistry*

Substances

  • Antibodies
  • Chelating Agents
  • Coordination Complexes
  • Metals
  • Oligonucleotides
  • Oligopeptides
  • Radiopharmaceuticals