Chemistry Reference
In-Depth Information
the radIopharmaceutIcal chemIstry of
GallIum(III) and IndIum(III) for spect ImaGInG
Jonathan R. Dilworth
Department of Chemistry, University of Oxford, Oxford, UK
Sofia I. Pascu
Department of Chemistry, University of Bath, Bath, UK
7.1
IntroductIon to GallIum and IndIum chemIstry
The radiochemistry-relevant coordination chemistry of gallium and indium provides an interesting contrast to that of technetium
and rhenium highlighted in Chapter 6. The similarities and differences have been highlighted in a fairly recent review by Zubieta
et al. on molecular imaging [1]. Another review compared the coordination chemistry of technetium and indium [2], and the uses
of
99m
Tc and
111
In for the detection of inflammation/infection were compared in a review of the molecular imaging of these dis-
eases [3]. The radiopharmaceutical chemistry of Ga and In was included in a recent, comprehensive review that covered both
coordination chemistry and applications in diagnostic SPECT imaging [4].
Only the trivalent oxidation state is realistically accessible for Ga and In in aqueous, biocompatible, media. There is gen-
erally little π-bonding to stabilise Ga or In ligand bonds, and compounds with monodentate ligands tend to undergo rapid
exchange reactions. Stabilities of the level needed for radiopharmaceuticals can only be achieved through polydentate
ligands, preferably with substituents that provide steric shielding and additional kinetic stabilisation. Although predomi-
nantly classified as hard metals with a preference for N and O, both also show good stabilities with anionic S donors. The
octahedral ionic radii of the metals differ considerably (Ga = 62 pm, In = 92 pm); this impacts the stability of macrocyclic
ligands where matching of the ionic radius of the metal ion to the size of the cavity within the ligand is important in the
design of radiotracers for SPECT imaging. The ionic radius of Ga(III) is very similar to that of Fe(III), and the biological
systems designed to sequester Fe(III) also bind Ga(III) very effectively. The smaller ionic radius of Ga relative to In also
creates a stronger bond to water molecules, and water exchange rates for Ga are noticeably slower. However, this difference
does not impact significantly on the relative rates of complexation of Ga and In to polydentate ligands, and similar radiola-
belling conditions can be used for both. Coordination numbers for Ga complexes used in a radiopharmaceutical context vary
between 4 and 6, whereas the larger In can accommodate 7 or 8 donors.
This chapter focuses on the coordination chemistry of the polydentate ligands most used for radiopharmaceutical appli-
cations and gives selected examples of the applications of the radiolabelled complexes in imaging and therapy.
7.1.1
the radioisotopes
Table 7.1 summarises the nuclear properties of the isotopes discussed in this chapter. Both Ga and In have a wide range of
accessible radioisotopes but only
67
Ga,
68
Ga, and
111
In have been used extensively in SPECT imaging. The applications of
68
Ga
for PET chemistry are discussed elsewhere in this volume (Chapter 5).
67
Ga is produced commercially by the proton irradiation
