14.4 General Radiolabeling Procedure
with
18
F for Peptides
Over the past few decades, the development of the combinatorial chemistry and
phage display technology allowed to discover novel bioactive peptide sequences In
particular, the phage display has provided about 160 sequences of tumor targeting
peptides [41]. Based on high expectation to use these new peptide sequences as the
molecular imaging probe or new drug candidates, development of peptide radiolabeling reactions with various radioisotopes came to be an important research topic
for nuclear molecular imaging, diagnosis, and therapy [42].
18 F labeled peptides can be prepared through two synthetic pathways as shown in
Fig. 14.4. Firstly, the direct
18 F labeling procedure can be applied to produce
18 F
labeled peptides by radiofluorination with no-carrier-added (n.c.a.)
18 F. This direct
labeling reaction requires the harsh strong basic reaction conditions in organic
solvent, which is known to be not suitable for maintain the integrity of these peptides
molecules. As a result, the direct radiofluorination reaction was hardly used to
incorporate
18 F atom into the peptides, as the bioactive peptides are sure to be
denatured or decomposed under this direct
18 F labeling scheme (Fig. 14.4a) [43, 44].
Secondly, the other
18 F labeling of peptides is an indirect labeling method with
stable
18 F labeled building blocks (referred to prosthetic groups or synthons) by a
conjugation reaction. This indirect synthetic pathway is generally suitable to synthesize
18 F-labeled peptides via the conjugation reactions between the peptides and
Fig. 14.3 a Bioorthogonal SPAAC reaction for the in situ synthesis of
18
F-labeled MSNs in a
living specimen for the MSNs pretargeting PET-imaging in tumor mice model. b PET-CT images
of
18
F-labeled azide in a U87MG tumor-xenograft mouse administrated only
18
F-labeled azide
alone (non-pretargeted). c PET-CT images in a U87MG tumor-xenograft mouse pre-treated
ADIBO-PEG-MSNs 24 h earlier (pretargeted procedure) at 15, 30, and 60 min after injection of
18
F-labeled azide. T = tumor, K = kidneys. Adapted from [40] with permission
14 Bioorthogonal Reaction for Fluorine-18 Labeling
267
with
18
F for Peptides
Over the past few decades, the development of the combinatorial chemistry and
phage display technology allowed to discover novel bioactive peptide sequences In
particular, the phage display has provided about 160 sequences of tumor targeting
peptides [41]. Based on high expectation to use these new peptide sequences as the
molecular imaging probe or new drug candidates, development of peptide radiolabeling reactions with various radioisotopes came to be an important research topic
for nuclear molecular imaging, diagnosis, and therapy [42].
18 F labeled peptides can be prepared through two synthetic pathways as shown in
Fig. 14.4. Firstly, the direct
18 F labeling procedure can be applied to produce
18 F
labeled peptides by radiofluorination with no-carrier-added (n.c.a.)
18 F. This direct
labeling reaction requires the harsh strong basic reaction conditions in organic
solvent, which is known to be not suitable for maintain the integrity of these peptides
molecules. As a result, the direct radiofluorination reaction was hardly used to
incorporate
18 F atom into the peptides, as the bioactive peptides are sure to be
denatured or decomposed under this direct
18 F labeling scheme (Fig. 14.4a) [43, 44].
Secondly, the other
18 F labeling of peptides is an indirect labeling method with
stable
18 F labeled building blocks (referred to prosthetic groups or synthons) by a
conjugation reaction. This indirect synthetic pathway is generally suitable to synthesize
18 F-labeled peptides via the conjugation reactions between the peptides and
Fig. 14.3 a Bioorthogonal SPAAC reaction for the in situ synthesis of
18
F-labeled MSNs in a
living specimen for the MSNs pretargeting PET-imaging in tumor mice model. b PET-CT images
of
18
F-labeled azide in a U87MG tumor-xenograft mouse administrated only
18
F-labeled azide
alone (non-pretargeted). c PET-CT images in a U87MG tumor-xenograft mouse pre-treated
ADIBO-PEG-MSNs 24 h earlier (pretargeted procedure) at 15, 30, and 60 min after injection of
18
F-labeled azide. T = tumor, K = kidneys. Adapted from [40] with permission
14 Bioorthogonal Reaction for Fluorine-18 Labeling
267