Chemistry Reference
In-Depth Information
R
R:
+
Cl
= In(Cl)TTAP
19
N
N
N
In
R
R
+
N
N
= In(Cl)TTAP
20
N
R
R
1
R
1
NH
N
R
1
=CH
3
CHOH, R
2
=CH
2
CH
2
CO
2
H; hematoporphyrin
R
1
= H, R
2
= H; deuteroporphyrin
N
HN
R
2
O
OH
21
fIGure 7.12
Gallium and indium porphyrins, deutero- and haemato-porphyrins.
NH
HN
NH
2
H
2
N
H
H
HN
NH
22
fIGure 7.13
A cryptand ligand used to bind Ga(III) giving highly kinetically stable complexes.
7.2.8 n
6
donor ligands
Cryptand ligands (Figure 7.13) have been known for many years and form extremely stable complexes with a range of metal
ions [84, 85]. The ligand system has now been shown to form very robust tricationic complexes with Ga(III), and an X-ray
crystal structure shows distorted N
6
octahedral coordination about the metal. The conjugate with two molecules of a cyclic
RGD peptide attached via an extended linker was radiolabelled in high yield with
68
Ga at 80 °C for 35 min. PET studies
in vivo
on a xenografted mouse model showed good specific accumulation of
68
Ga in tumours with high integrin expression [86].
7.3
auGer electron therapy wIth
111
IndIum
The most common form of treatment of tumours involves external beam X-ray therapy (XRT) and is used in approximately
50% of patients with proven efficacy. It is, however, not as effective when dealing with metastases or situations where
the cancer has spread. The alternative of using
186
Re or
188
Re bioconjugates for targeted radionuclide therapy has been
discussed above. The Auger electrons emitted by the decay of
111
In offer an additional way to achieve DNA damage and
eventual cell death. Their penetration range is only 1 to 25 nm and to have maximum impact on DNA, the
111
In needs ideally
to be localised in the nucleus. A recent review provides an excellent summary of the field of Auger electron radiotherapy
[87]. Earlier reviews are also available [88-90]. Our account is not comprehensive but presents some examples of the strat-
egies employed in
111
In-based therapeutic applications.
Somatostatin analogues bind to sstrs on the external surface of cells and are thence internalised and locate in the nucleus.
Nuclear uptake can however, be increased markedly by using a nuclear localising peptide (NlS) [91]. The conjugate
