Chemistry Reference
In-Depth Information
NO
2
SH
N
CO
2
H
N
N
NH HN
N
HO
2
C
N
N
N
N
N
HS
SH
HO
2
C
OH
HO
O
O
NO
2
p-NO
2
-Bn-H
2
dedpa
TACN-TM
p-NO
2
-Bn-PCTA
HO
HO
HO
O
HO
O
O
OH
N
N
HO
N
N
O
O
OH
O
OH
OH
OH
HBED
HBED-CC
O
O
HN
OH
N
N
N
N
O
P
O
O
OH
O
OH
O
HO
O
N
HN
O
O
HO
OH
N
N
N
P
P
O
HO
OH
O
OH
CP256
PrP9 (TRAP)
O
fIgure 5.10
Examples of several promising and novel Ga(III) chelators, most of which were first published in the last few years.
Ga(III) for transferrin. Trans-chelation by transferrin can be evaluated through
in vitro
human serum and/or
apo
-transferrin
competition experiments, which can be used to estimate the practical stability of metal-chelator complexes
in vivo
[113]
.
Because transferrin in human serum is typically only 30% saturated with iron(III) (with ~70% vacant binding sites), it can
bind additional metal ions without the need for direct competition with iron(III) [118, 119]. Iron(III)-transferrin stability
constants have been reported as log
K
1
* = 22.8 and log
K
2
* = 21.5, showing the highest stability constants of all of the metal
ions discussed here (as would be expected because transferrin is an iron transport protein) [70]. The gallium-transferrin sta-
bility constants have been reported as log
K
1
= 20.3 and log
K
2
= 19.3 for the two metal ion binding sites found in the
C
-terminus and
N
-terminus, respectively [38]. Free
68
Ga can be observed to accumulate in high levels in the lungs, liver,
spleen, and bone, a direct consequence of its exceptionally strong affinity for the iron transport protein transferrin [78].
5.5.4
68
gallium radiometallation protocols
As previously noted, the short half-life of
68
Ga (68 minutes) lends itself to fast radiolabelling conditions with minimal post-
labelling purification. similar to the examples given for Y(III), macrocycles such as dOTA typically require heating [120-
123], and acyclic chelators such as hBEd-CC and dTPA (also dTPA derivatives like mx-dTPA and ChX-A″-dTPA), and
even the macrocycle nOTA use mild labelling conditions [109, 124, 125]. The peptide-conjugate
68
Ga-dOTA-TOC has
been labelled with
68
Ga that was directly eluted from a generator system with no pre-labelling purification or concentration
of the generator eluent (10 minutes at 100 °C, purified by C18 cartridge), which is an attractive use of the convenient
generator system [87].
