Chemistry Reference
In-Depth Information
the radIopharmaceutIcal chemIstry
of technetIum and rhenIum
Jonathan R. Dilworth
Department of Chemistry, University of Oxford, Oxford, UK
Sofia I. Pascu
Department of Chemistry, University of Bath, Bath, UK
6.1 IntroductIon
6.1.1 technetium chemistry
The position of technetium in the centre of the transition metal block enables it to exhibit a wide range of oxidation states
(−1 to +7) and coordination numbers (generally 4 to 7). The accessibility to both high and low oxidation states and the avail-
ability of d orbitals of appropriate symmetry means that multiple bonding via σ and π combinations can play an important
role in complex stabilisation. This ability to form multiple bonds means that even monodentate ligands can be sufficiently
robust to survive in a biological environment.
Within a radiopharmaceutical context, the highly appropriate nuclear decay properties of
99m
Tc coupled with the availability
of a generator system and facile radiolabelling has meant that nuclear medicine uses this isotope extensively. In fact, the vast
majority of nuclear medical investigations worldwide are still carried out with technetium, and it has been estimated that world-
wide at least 70,000 technetium SPECT scans are made daily. In the USA alone some 19 million Tc scans were performed in
2007, and approximately half of these involved cardiac imaging. Such numbers are difficult to extrapolate with any accuracy,
but it is realistic to assume that around 30-40 million technetium scans are conducted annually across the world.
Although publications on technetium chemistry have remained fairly constant over the past decade, the number of papers in
nuclear medicine journals has declined markedly. This indicates that while interest in the coordination chemistry of technetium
chemistry and animal studies has been sustained, translation to the clinical and commercial arenas has all but disappeared. For
chemistry, the regulatory difficulties of working with the long-lived
99
Tc radioisotope has means that there are now few centres
worldwide with the capability of complete chemical characterisation of technetium complexes, and this does not augur well for
the future of fundamental research. Another important factor is that the landscape of molecular imaging has changed dramati-
cally over the past decade with the advent of PET. This has had a significant impact on the development and clinical translation
of technetium-based imaging agents. Part of the driving force toward PET using isotopes such as
18
F and
11
C rather than SPECT
has been the obvious advantage of being able to radiolabel a targeting molecule with minimal changes in the overall structure,
which assumes particular importance in brain imaging where translocation across the BBB is crucial. However, this and the
greater sensitivity and ease of quantification of PET has to be offset against the substantial investment in cyclotrons, hot cells,
and automated synthesis units and the technically demanding radiolabelling procedures. It seems likely that this technology will
be restricted to highly developed areas for the foreseeable future despite the pressing healthcare needs of the poorer countries
[1]. The ultimate decision on whether to use PET or SPECT depends on balancing a number of issues, but it is not axiomatic
