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, eg67Ga, 99mTc, 111In, 177Lu) and positron emission tomography (PET, eg68Ga, 64Cu, 44Sc, 86Y, 89Zr), as well as therapeutic applications (eg47Sc, 114mIn, 177Lu, 90Y, 212/213Bi, 212Pb, 225Ac, 186/188Re) 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

Matching chelators to radiometals for radiopharmaceuticals.

Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides.

PET (positron emission tomography) is a powerful diagnostic and imaging technique which requires short-lived positron emitting isotopes. The most commonly used are accelerator-produced (11)C and (18)F. An alternative is the use of metallic positron emitters. Among them (68)Ga deserves special attention because of its availability from long-lived (68)Ge/(68)Ga generator systems which render (68)Ga radiopharmacy independent of an onsite cyclotron. The coordination chemistry of Ga(3+) is dominated by its hard acid character. A variety of mono- and bifunctional chelators have been developed which allow the formation of stable (68)Ga(3+)complexes and convenient coupling to biomolecules. (68)Ga coupling to small biomolecules is potentially an alternative to (18)F- and (11)C-based radiopharmacy. In particular, peptides targeting G-protein coupled receptors overexpressed on human tumour cells have shown preclinically and clinically high and specific tumour uptake. Kit-formulated precursors along with the generator may be provided, similar to the (99)Mo/(99m)Tc-based radiopharmacy, still the mainstay of nuclear medicine.

/pdf/68ga-pet-a-powerful-generator-based-alternative-to-cyclotron-jpajj92dwr.pdf

68Ga-PET: a powerful generator-based alternative to cyclotron-based PET radiopharmaceuticals

Synthetic and structural aspects of the chemistry of saturated polyaza macrocyclic ligands bearing pendant coordinating groups attached to nitrogen

Radiometals possess an exceptional breadth of decay properties and have been applied to medicine with great success for several decades. The majority of current clinical use involves diagnostic procedures, which use either positron-emission tomography (PET) or single-photon imaging to detect anatomic abnormalities that are difficult to visualize using conventional imaging techniques (e.g., MRI and X-ray). The potential of therapeutic radiometals has more recently been realized and relies on ionizing radiation to induce irreversible DNA damage, resulting in cell death. In both cases, radiopharmaceutical development has been largely geared toward the field of oncology; thus, selective tumor targeting is often essential for efficacious drug use. To this end, the rational design of four-component radiopharmaceuticals has become popularized. This Review introduces fundamental concepts of drug design and applications, with particular emphasis on bifunctional chelators (BFCs), which ensure secure consolidation of the radiometal and targeting vector and are integral for optimal drug performance. Also presented are detailed accounts of production, chelation chemistry, and biological use of selected main group and rare earth radiometals.

Radioactive Main Group and Rare Earth Metals for Imaging and Therapy

Structure and Solution Stability of Indium and Gallium Complexes of 1, 4,7‐Triazacyclononanetriacetate and of Yttrium Complexes of 1,4,7,10‐ Tetraazacyclododecanetetraacetate and Related Ligands: Kinetically Stable Complexes for Use i

Improved Tumor Targeting with Recombinant Antibody‐Macrocycle Conjugates.

Synthesis and Complexation Behaviour of an Effective Octadentate Complexone 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrakis(methylene( meethylphosphinic acid)).

A. Harrison

Papers

Structure and Solution Stability of Indium and Gallium Complexes of 1, 4,7‐Triazacyclononanetriacetate and of Yttrium Complexes of 1,4,7,10‐ Tetraazacyclododecanetetraacetate and Related Ligands: Kinetically Stable Complexes for Use i

Improved Tumor Targeting with Recombinant Antibody‐Macrocycle Conjugates.

Synthesis and Complexation Behaviour of an Effective Octadentate Complexone 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrakis(methylene( meethylphosphinic acid)).