Chemistry Reference
In-Depth Information
(
16
O
15
OH)
15
OH
1. [
15
O]O
2
/N
2
cat. AIBN/n-Bu
3
SnH
2. PhCF
3
/C
10
F
18
/2-C
4
H
9
OH,
PPh
3
, 80°C
15
O
16
OH
H
I
O
O
O
O
H
HO
H
HO
H
HO
H
HO
+
+
OH
OH
OH
OH
[
15
O]DG
Bu
3
SnH and
PPh
3
(in situ)
[
15
O]H
2
O + [
16
O]H
2
O
scheme 4.34
Free radical synthesis of 6-[
15
O]-2-deoxy-D-glucose ([
15
O]Dg) from iodinated sugar and [
15
O]O
2
.
[
15
O]Butanol, prepared via the reaction of [
15
O]O
2
tributyl borane [179, 180], has proven to be superior to [
15
O]H
2
O in
measuring cerebral blood flows and performing neuroactivation studies [181]. Another recent example reports the practical
one-step preparation of
15
O labelled deoxyglucose O6-[
15
O]-2-deoxy-D-glucose ([
15
O]Dg) within a 7 min. reaction time
(scheme 4.34) [182].
The synthesis was carried out using the iodinated precursor under mild reaction conditions that importantly removed the
need for protecting the hydroxyl groups on the sugar. By circumventing a deprotection step, it was then possible to reduce
the overall reaction time from hours to minutes. A specially adapted hot-air jacket reaction vessel equipped with a sintered
glass bottom introduced the O-15 gas into the liquid reagents as fine bubbles. Typical decay-corrected radiochemical purity
of the labelled [
15
O]Dg was found to be >70%. [
15
O]Dg was used to perform sequential [
15
O]Dg-[
15
O]H
2
O-[
18
F]FDg mea-
surements and PET images showing accumulation in the heart, kidneys, and bladders of animal models.
4.5
concLusIons
Over the past two decades there has been a diverse range of chemistry applied to the synthesis of C-11, N-13, and O-15 radio-
labelled compounds for PET. As new chemistry is adopted from the mainstream chemical literature and specifically applied
to radiolabelling, new possibilities have emerged for labelling different functional groups and labelling in different atomic
positions within target molecules. The application of transition metal cross-coupling reactions and carbonylation methods are
prime examples. Equally, the development of new technologies (e.g., microfluidics, microwave, and UV-photochemistry) and
the improvement in automated procedures have had an important impact on the safety and the reliability of labelling proce-
dures. The application of technology and its commercialisation is an important driver in this regard and can have an important
influence on developing new radiochemistry. An example of this is the new radiochemistry that has emerged around
11
CH
2
O,
11
CH
3
NO
2
, and
11
Cs
2
, which is a direct result of the now routine production of C-11 methyl iodide. The development of chem-
istry with C-11, N-13, and O-15 is ultimately driven by their application in PET imaging and the resultant need to radiolabel
an ever-wider range of compounds. There are still many challenges in this area with regards to widening reaction scope, the
development of novel precursor synthesis, reducing reaction times and improving radiosynthesis reliability.
reFerences
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Angew. Chem. Int. Ed.
47
, 8998-9033 (2008).
[2] J. s. Fowler and A. P. Wolf,
Acc. Chem. Res
.
30
, 181-188 (1997).
[3] s. M. Ametamey, M. Honer and P. A. schubiger,
Chem. Rev.
108
, 1501-1516 (2008).
[4] C. Aubert, C. HuardPerrio and M. C. Lasne,
J. Chem. Soc., Perkin Trans. 1
2837-2842 (1997).
[5] C. Perrio-Huard, C. Aubert and M. C. Lasne,
J. Chem. Soc., Perkin Trans. 1
311-316 (2000).
[6] s. y. Lu, J. s. Hong and V. W. Pike,
J. Labelled Compd. Radiopharm.
46
, 1249-1259 (2003).
[7] J. van den Hoff, W. Burchert, A. r. Borner, H. Fricke, g. Kuhnel, g. J. Meyer, D. Otto, E. Weckesser, H. g. Wolpers and
W. H. Knapp,
J. Nuc. Med.
42
, 1174-1182 (2001).
[8] D. E. Ponde, C. s. Dence, N. Oyama, J. Kim, y. C. Tai, r. Laforest, B. A. siegel and M. J. Welch,
J. Nuc. Med.
48
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[9] r. J. Davenport, K. Dowsett and V. W. Pike,
Appl. Radiat. Isot.
48
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