Chemistry Reference
In-Depth Information
O
NH
HO
N
O
O
HO
HO
HO
O
OH
18
F
18
F
1
[
18
F
]FDG
2
[
18
F
]FLT
FIGURE 7.1
Two labeled carbohydrates used in PET. (See color plate section.)
and phosphorylation prevents glucose from being released. Since the 2
hydroxyl
group is absent in FDG, it is not further metabolized in cells and accumulates. Other
radiotracers are now in use such as 3
-deoxy 3
-[
18
F]fluorothymidine (FLT) (
2
)or
fluorocholine (FC) both for tumor detection applications (Figure 7.1).
FDG as well as FLT and FC have been used in a number of clinical studies but
have some drawbacks and are limited to some pathologies. Major advances in PET
imaging will undoubtedly come from new, more sophisticated radiotracers specially
designed for a given application. The design of a new radiotracer comprises the
selection of an appropriate target and of a molecule able to interact with the target,
two choices relevant to biomedicine and molecular biology. The determination of the
radioelement and of its place in the molecule is the second step in the radiotracer
design, relevant to radiochemistry. Finally, the synthetic plan toward the radiotracer
synthesis is relevant to organic chemistry.
As shown in Figure 7.2, two main strategies are available for the introduction
of the radioelement either by formation of a covalent bond (for fluorine or carbon,
paths a and b) or by the formation of a complex (for technetium, gallium, indium, or
copper, path c and d). Regarding the formation of covalent bonds shown on the left-
hand side of Figure 7.2, there is again two ways to introduce the radioelement, either
directly, by modification of the active molecule (direct labeling path a, Fig. 7.2), or by
coupling the bioactive molecule to a small molecule bearing the radioelement. This
small molecule is called a prosthetic group. The coupling reaction (path b Fig. 7.2)
is then crucial to the synthesis. Given the half-life of the radioelement, the labeling
reaction must be a fast reaction, ideally performed within 10-20 minutes. When using
a prosthetic group, its labeling and the coupling reaction should take place within
the same time range. Moreover, the coupling reaction must be efficient in order to
be sure that the totality of the prosthetic group is coupled to the active molecule,
that is, all the radioactivity is located on the expected radiotracer, ideally without
the need to extensively purify the radiotracer. As already mentioned, radiotracers of
the future will certainly be elaborated around complex biomolecules like peptides,
proteins, carbohydrates, or nucleic acids, all of them being rather sensitive compounds
[3-5]. The use of prosthetic groups should be the method of choice to label these
biomolecules. One current challenge in the field of radiochemistry is to design new
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