Chemistry Reference
In-Depth Information
that PET will be the best choice in all situations. For animal imaging the modern SPECT imaging systems can achieve better
resolution than PET, although the sensitivity remains some 15 times lower as shown
inter alia
by imaging of phantoms and
comparative tumour imaging with
99m
Tc or
18
F labelled nanoparticles [2]. In the clinical arena it has been shown that for SPECT,
at least in the case of
99m
Tc diphosphonate bone scans, sophisticated computer analysis techniques can be applied to permit
accurate quantification [3]. Comparative studies of PET and SPECT agents in imaging patients with Parkinson's disease [4] or
chest lesions [5] have shown that the SPECT and PET data provide equally useful diagnostic information.
6.1.2
rhenium
Rhenium is located in the same transition metal group as technetium, and the two elements form many isostructural
complexes. This leads to non-radioactive Re complexes frequently being used as models for technetium for structure and
biological characteristics such as substrate binding. However, there are also some significant differences in their chemistries.
As a third row transition element, rhenium complexes are harder to reduce and easier to oxidise than their technetium coun-
terparts. As a consequence, the formation of perrhenate through oxidation is favoured more than for pertechnetate, and
cationic rhenium complexes in high oxidation states with non-reducing ligands frequently contain perrhenate anions.
Rhenium complexes are also more kinetically inert than their technetium analogues and complexation often requires
more forcing conditions including heating. This can create problems in terms of labelling heat sensitive biomolecules
with rhenium radioisotopes. Insertion of rhenium into a bifunctional chelator (BFC) may have to be carried out prior to
conjugation to the biomolecule (preconjugation labelling). This increases the length of the labelling procedure and the risk
of radiation exposure. It still remains a challenge to produce BFCs that can be labelled with a rhenium radioisotope at room
temperature. A useful review of the BFCs available for the radiorhenium labelling of biomolecules is available [6].
In addition to its role as a surrogate for technetium, the major interest in rhenium lies in the potential therapeutic applications
of the β-emitting
186
Re and
188
Re radioisotopes. The use of very toxic radioisotopes places stringent requirements on the stabil-
ities of the complexes and the efficiency of targeting. As a consequence, the development of rhenium-based therapeutic agents
has been much slower than for technetium imaging agents, and testing has been generally confined to animal studies. In fact,
the only regular clinical use for rhenium complexes is that of the rhenium diphosphonate complex
188
ReHEDP for the palliation
of bone pain in terminal cancer patients [7], although a number of other compounds have undergone limited clinical trials.
6.1.3
radioisotopes of technetium and rhenium
As discussed above, in addition to the ideal nuclear properties, the ready availability of technetium is an important contrib-
uting factor to its popularity. However, a significant problem arose around 2000 with a potential shortage of technetium-99 m
arising from the gradual decommissioning of nuclear reactors, which provided the bulk of the
99
mo for the clinical generator
systems as a by-product of
235
U fission. By 2009 the five major reactors producing
99
mo were nearing the end of their produc-
tive lives [8]. However, a number of groups showed that
99m
Tc could be satisfactorily produced in medium energy cyclotrons
in TBq quantities by the
100
mo(p,2n)
99m
Tc nuclear reaction and that the imaging characteristics of the isotope were identical
with that produced from a generator [9]. It therefore appears that supplies of the
99m
Tc isotope can be secured into the future.
The properties of the relevant isotopes of Tc and Re are summarised in Table 6.1.
The positron emitting isotope
94m
Tc can be cyclotron produced by the
94
mo(p,n) nuclear reaction in good yields and purity
[10]. There was surge of interest in the use of this radioisotope in the 1990s based on the concept that this would provide
PET analogues of existing Tc agents. It was shown, for instance, that the antibody fragment 'CEA-scan' could be radiola-
belled in good yield in a directly analogous manner to
99m
Tc [11]. The
94m
Tc labelled sestamibi compound was also used to
image multidrug resistance in mice [12]. However, the decay characteristics of
94m
Tc are not ideal, and the high (2.47 meV)
table 6.1
radioisotopes of technetium used in Imaging or therapy.
Isotope
Half-life
Decay Products
Production
99m
Tc
6h
γ (140 KeV, 98.6%)
γ (142.7 KeV, 1.4%
Auger (2.1 KeV)
99
mo/
99m
Tc generator
94m
Tc
52min
β
+
(2.4 meV, 72%)
Cyclotron from
94
mo
186
Re
90h
β (1.07 meV, 71%)
γ (137meV, 9%)
Reactor
188
Re
17h
β (2.1meV, 100%)
γ (155meV, 15%)
188
W/
188
Re generator
