Chemistry Reference
In-Depth Information
5.4.5
86
yttrium summary
due to the ideal therapeutic properties of
90
Y, a great deal of work has focused on its incorporation into cancer-treating radio-
pharmaceuticals. having no significant β
+
or γ emissions,
90
Y-based agents require a matched isotope pair to be used together
for imaging and dosimetry.
86
Y is an optimal candidate as a PET imaging surrogate for
90
Y because their chelate complexes
have identical chemical and physiological properties. Because
86
Y and
90
Y form chemically identical chelate complexes, they
are considered bioequivalent as demonstrated by
86
Y providing more accurate dosimetry data than other non-identical surro-
gates such as
111
In. Aside from use as a dosimetry surrogate for
90
Y,
86
Y may not be an ideal candidate for mainstream
imaging applications as it has a high-energy β
+
emission that results in lower resolution images (although corrections can be
applied) and high-energy γ emissions that expose patients to significant absorbed doses.
5.5
68
gallIum radIometal Ion propertIes
68
Ga has a short half-life of 68 minutes, a high positron abundance of 90%, and robust coordination chemistry with many
ligands. Ga(III) is an acidic group 13 metal ion (pKa = 2.6) that is redox stable in aqueous conditions. Ga(III) hydrolyses to
insoluble Ga(Oh)
3
between ph 3-7, has a very high affinity for hydroxide ions, and tends to deligate above ph 7 to form the
soluble gallate anion [Ga(Oh)
4
]
-
[16]. Ga(III) has the slowest water exchange rate of all the metal ions discussed in this
chapter and prefers to form complexes with coordination numbers of 4 to 6. The most promising chelating agents for gallium
are hexadentate to maximise complex stability, typically adopting a distorted octahedral geometry. The hard character of the
Ga(III) ion lends preference to hard donor atoms such as carboxylate-oxygens, amine-nitrogens, phenolate-oxygens, and
hydroxamate-oxygens. The short 68-minute half-life of
68
Ga makes fast, low temperature radiometallation with BFC agents
a high priority.
66
Ga is also a PET isotope of Ga(III); however, its high energy β
+
emission of 4150 keV and lower positron
abundance (56%) leads to poor image resolution.
66
Ga also has a high-energy γ emission (4000 keV) that exposes patients to
very high absorbed doses. These serious limitations, combined with the lack of a portable generator system and various pro-
duction/purification problems have led to clinical applications of
66
Ga being extremely limited [18].
One negative property of
68
Ga is its relatively high positron energy (~1880 keV), which results in lower resolution images
when compared to lower β
+
energy emitters such as
64
Cu and
89
Zr (656 and 897 keV, respectively). however, the positron
abundance (favourable branching ratio) of 90% for
68
Ga is much higher than that of
64
Cu,
89
Zr, and
86
Y (19%, 23%, and 33%,
respectively), which means that lower amounts of activity and/or shorter image acquisition times can be used. Another
favourable nuclear decay property of
68
Ga is its lack of high-energy γ emissions (unlike
86
Y,
89
Zr, and
124
I), which allows for
easier data collection and lower patient absorbed doses.
68
Ga is obtained through a
68
Ge-based generator system using a
stationary-phase substrate such as Al
2
O
3
, CeO
2
, snO
2
, TiO
2
, or ZrO
2
[84].
68
Ga(III) is typically eluted with a dilute hCl solu-
tion, while the
68
Ge(IV) is retained on the generator column [84]. no
68
Ge/
68
Ga generator system is currently approved as
having pharmaceutical-grade eluent, which limits translation of
68
Ga-based imaging agents into the clinic [85, 86]. The
68
Ge/
68
Ga generator system provides a long shelf life of ~1 year and allows easy mobilisation to hospital radiopharmacies
regardless of their proximity to cyclotron or nuclear reactor production sites. The easy distribution of
68
Ga through a
long-lived generator system is one of the reasons that
68
Ga is thought by many people to be the most attractive radiometal
discussed in this chapter. Many
68
Ga-based agents such as
68
Ga-dOTA-TOC,
68
Ga-dOTA-nOC, and
68
Ga-dOTA-TATE
have been studied and have shown excellent promise for use in diagnostic nuclear medicine, but without an approved
generator system they are limited in their widespread clinical application [87-89].
5.5.1
clinical trials Based on
68
gallium
There are currently no FdA-approved radiopharmaceuticals that utilise
68
Ga; however,
67
Ga-citrate is an FdA-approved
sPECT agent for imaging of various cancers and inflammatory lesions. Once injected into a patient,
67
Ga is easily trans-
metallated from the weak citrate chelate and becomes ~99% transferrin bound.
68
Ga-citrate is currently in clinical trials in the
European union for use in PET imaging of inflammatory infectious diseases [53]. There are several BFC systems in clinical
trials in north America and the European union that utilise
68
Ga [53].
68
Ga-dOTA-TOC (dOTA-d-Phe1-Tyr-octreotide) is a
labelled somatostatin analogue (octreotide) that is in clinical trials as a kit for imaging and dosimetry, to be used as a
theranostic agent with the therapeutic isotopes
90
Y/
177
lu (with dOTA-TOC or dOTA-TATE, Figure 5.8) [53, 87-89].
dOTA-TOC utilises the cyclic peptide octreotide, which binds to somatostatin receptors that are overexpressed on neu-
roendocrine tumours [88, 90].
68
Ga-dOTA-TOC PET has been shown to be even more effective at identifying cancerous
lesions than are CT or MRI [91]. Recent work has also shown
68
Ga-dOTA-TOC to be more sensitive for detecting neuroen-
docrine tumours than the FdA-approved sPECT agent Octreoscan
TM
(
111
In-dTPA-octreotide) [92, 93]. The octreotide-based
