An efficient and expedient method for the synthesis of 11C- labeled α-aminoisobutyric acid: A tumor imaging agent potentially useful for cancer diagnosis

Article abstract of DOI:10.1016/j.bmcl.2011.02.065

We describe the synthesis of ¹¹C-labeled α-aminoisobutyric acid 2 from iodo[¹¹C]methane and methyl N-(diphenylmethylen)-d,l- alaniate (5). The tetrabutylammonium fluoride (TBAF)-promoted α-[ ¹¹C]methylation of sterically h

Full text of DOI:10.1016/j.bmcl.2011.02.065

Bioorganic & Medicinal Chemistry Letters 21 (2011) 2437–2440
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
An efficient and expedient method for the synthesis of 11C-labeled
a-aminoisobutyric acid: A tumor imaging agent potentially useful for cancer
diagnosis
Koichi Kato a, , Atsushi B. Tsuji b, Tsuneo Saga b, Ming-Rong Zhang a
⇑
a Department of Molecular Probes, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
b Department of Molecular Diagnosis, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
a r t i c l e i n f o
a b s t r a c t
We describe the synthesis of 11C-labeled
N-(diphenylmethylen)-D,L-alaniate (5). The tetrabutylammonium fluoride (TBAF)-promoted a
ylation of sterically hindered analog 5 was a key step in our synthesis process. Total radiochemical
conversion of 2 was high and a remote-controlled synthesis was carried out. A comparative tumor
positron emission tomography (PET) imaging study using the same model mouse showed higher uptake
of 2 than with 11C-labeled methionine and [18F] fluorodeoxyglucose (FDG).
a
-aminoisobutyric acid 2 from iodo[11C]methane and methyl
Article history:
-[11C]meth-
Received 7 January 2011
Revised 14 February 2011
Accepted 15 February 2011
Available online 18 February 2011
Keywords:
Isotopic labeling
Carbon-11
Ó 2011 Elsevier Ltd. All rights reserved.
Tumor imaging
Positron emission tomography
AIB
Isotopic labeling of amino acids with positron-emitting radio-
nuclides is an important research topic for positron emission
tomography (PET), a non-invasive imaging technology.1 A variety
of natural and unnatural amino acids labeled with carbon-11 and
fluorine-18 have been synthesized and used for tumor imaging
and brain studies.1,2 Although labeled amino acids are useful probes
to perform a large variety of PET studies, they are not readily synthe-
sized by accessible methodologies, except for [methyl-11C]methio-
nine ( Fig. 1).1 As a result, only [methyl-11C]methionine is used
widely for cancer diagnosis; however, this compound is not ideal
for tumor imaging because of metabolic [11C]demethylation.1,2a
The development of convenient synthetic methods for the prepara-
tion of labeled amino acids is an important challenge in the area of
PET research.
O
OH
O
*
H
2N
OH
S
H2N
HO
HO
O
OH
OH
*
18F
* = 11C
[
methyl
-
11C]methionine
[
18F]FDG
[1-11C]AIB
Figure 1. Structures of [methyl-11C[methionine, [18F]FDG, and [1-11C]AIB.
context, 11C-labeled
suitable molecule for tumor imaging, because AIB is primarily
transported into viable cells via an A-type amino acid transporter
system and is metabolically stable in cells.4,5 The absence of a typ-
a
-aminoisobutyric acid ([11C]AIB, Fig. 1) is a
ical chiral center in amino acids at the a-position is advantageous
The increase in amino acid transporters activity is found in
many tumors. Such transporters are up-regulated during cell
growth and division in tumor cells; thus, its assessment in vivo
(which can be approached by tracer analysis using radio-labeled
amino acids) becomes a useful tool for the clinical diagnosis of can-
cer.3 In addition, a PET image of a labeled amino acid can describe
tumors more selectively as compared with PET images using 2-
deoxy-2-[18F]fluoro-glucose ([18F]FDG).1,2a,b Metabolically stable
amino acid analogs have become a focus for isotope incorporation,
because they can simplify the interpretation of PET images. In this
as this feature facilitates interpretation of PET images.
The usefulness of 11C-labeled AIB has been demonstrated in
human and animal studies in vitro and in vivo; however, its use
has not been widely developed because the labeling synthesis
approach of this compound is generally inaccessible and not
robust. Carbon-11-labeled AIB was first synthesized as [1-11C]AIB
by Bucherer–Strecker synthesis using
[ a
11C]cyanide ion as
11C-labeling agent.4a Human and animal PET studies were per-
formed using [1-11C]AIB synthesized by this method.5 However,
the [11C]cyanide ion is not a frequently used 11C-labeling agent.
Moreover, its synthesis requires the addition of carrier (non radio-
active) cyanide to compensate for its low reactivity. As a result, rig-
orous quality assurance programs to ensure the absence of toxic
⇑
Corresponding author.
E-mail address: katok@nirs.go.jp (K. Kato).
0960-894X/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2011.02.065

2438
K. Kato et al. / Bioorg. Med. Chem. Lett. 21 (2011) 2437–2440
amounts of cyanide are required. The syntheses of 11C-labeled AIB
using more convenient 11C-labeling agents such as iodo[11C]meth-
ane (1) and [11C]carbon dioxide have been reported.4b–d However,
organolithiums such as lithium diisopropylamide and methyl lith-
ium are used in these methods. Careful handling and stringent stoi-
chiometric requirements of organolithiums under the highly
diluted conditions of the labeling reaction limit the practical use
of 11C-labeled AIB. As a result, no PET studies have been reported
using 11C-labeled AIB synthesized by these methods. Further
development of new methodologies for carbon-11 labeling of AIB
have stalled, while AIB analogs such as [N-methyl-11C]MeAIB and
18F-labeled AIBs have been developed.6,7 The usefulness of AIB
has led to the development of analogous tracers that can be syn-
thesized more conveniently. Thus, the efficient and practical syn-
thesis of 11C-labeled AIB is still necessary for the use of this
compound as a diagnostic agent.
associated with continuous stirring of the reaction mixture, the use
of a dissolved base is preferable for the 11C-labeling synthesis. In
this regard, we have focused on the use of tetrabutylammonium
fluoride (TBAF), because the fluoride ion shows a basic character
when dissolved in organic solvents.12,13 A comparison with tetra-
butylammonium hydroxide (TBAOH), an active base of PT condi-
tions, was carried out, because the pKa values of the alanine
analogs (around 23) were in the upper range of where PT condi-
tions should be acceptable.8,14 Other typical soluble bases such as
triethylamine (TEA) and 1,8-diazabicyclo[5,4,0]undec-7-ene DBU
were also investigated.
We initially explored the
ester analog 3 by the reaction conditions: 3 (5
(10 mol), solvent (300 L), reaction time (90 s) and reaction
a
-[11C]methylation of the tert-butyl
mol), base
l
l
l
temperature (room temperature, rt). Two different reaction ap-
proaches that could be followed by remote-controlled synthesis
were introduced. Method A: 3 and base were mixed around
10 min before the addition of 1. Method B: base was added to
the mixture of 1 and 3. The results are summarized in Table 1.
Treatment of 1 and 3 with TBAF by methods A and B did not results
The use of Schiff base activated amino acid analogs is a primary
method in the preparation of higher amino acids by
a-alkylation
under non-radiolabeling conditions.8,9 Those methods have fre-
quently employed phase-transfer (PT) conditions, and reactions
are carried out under milder conditions. The benefit of using Schiff
base analogs for the preparation of 11C-labeled amino acids is that
the radioactive precursor 1 (a very frequently-used methylating
agent in PET chemistry) can be introduced in the synthetic scheme.
Consequently, we planned to synthesize 2-amino-[3-11C]isobutyric
in
a
-[11C]methylation neither using THF nor DMF. In contrast,
treatment of 1 and 3 with TBAF in DMSO using method A yielded
4 with excellent radiochemical conversion (78.1 4.8%). The reac-
tion was carried out using an excess of TBAF; therefore stringent
stoichiometry was not required for the fluoride-promoted
acid ([3-11C]AIB, 2) via
a
-[11C]methylation of Schiff base activated
a
-[11C]methylation of 3. In addition, it was practical to use a com-
alanine analogs (Scheme 1). Although the isotopic substitution at
the 3-position by carbon-11 affords two enantiomers, the influence
of a new chiral center is not expected to affect PET analyses.10
As compared with non-radiolabeling reactions, there are spe-
cific requirements that render the synthetic method suitable for
the preparation of widely used PET tracers.11 First, the use of eas-
ily-handled precursors is crucial for the success of a PET tracer syn-
thesis; therefore benzophenone imine analogs (R1, R2 = Ph) have
been chosen as Schiff base precursors. The pKa values of benzophe-
none imine analogs are considerably higher than the ones corre-
sponding p-chlorophenyl aldimine analogs (R1 = p-ClPh, R2 = H),
which are frequently-used building blocks for the preparation of
dialkylated amino acids under catalytic PT conditions.8 Thus, dial-
kylation of benzophenone imine-type glycine derivatives yielding
mercial solution of TBAFÁ3H2O for the
a
-[11C]methylation reaction.
-[11C]meth-
Dimethylsulfoxide was also a suitable solvent for the
a
ylation using TBAOH as a base. Treatment of 1, 3 and TBAOH in
DMSO by method B gave 4 with a 34.3 1.0% radiochemical con-
version. However,
using DBU or TEA in DMSO, neither following A nor B.
During the search of
-[11C]methylation in DMSO, remarkable
a
-[11C]methylation was not accomplished by
a
differences were observed between TBAF and TBAOH. The reaction
using method B gave better results than method A using TBAOH in
DMSO. The radiochemical conversion of 4 using TBAOH with meth-
od B was moderate. In contrast, efficient
a
-[11C]methylation of 3
was achieved using TBAF in DMSO using method A, whereas poor
radiochemical conversion was obtained by method B. When
TBAOH was used, the solution containing compound 3 immedi-
ately colored following the addition of the base; thus, the fast for-
mation of the corresponding anion of compound 3 (which could
the corresponding
a,a-symmetrical amino acids has been found
to be difficult.9b,c However, the stable properties of benzophenone
imine in air at room temperature for extended periods of time are
recognized to be more important for a widely-used labeling pre-
cursor.9a Second, one-pot syntheses processes in which time-con-
suming manipulation steps are skipped are essential to approach
11C-labeling strategies that involve more than two steps. One-pot
methods render remote-controlled PET tracer syntheses more
accessible and increase the radioactivity of the products. In this re-
gard, the choice of the reaction solvent is a critical parameter and
consequently, we have selected THF, DMF and DMSO as the reac-
tion solvents. These solvents accept the direct addition of an aque-
ous solution to the reaction mixture for the subsequent hydrolysis
of both the imine and ester groups.
contribute to the
used) was assumed in a first step.8a However, the color diminished
over time and was almost absent before the
-[11C]methylation
a
-[11C]methylation of 3 when method B was
a
reaction was initiated by the addition of 1 to the mixture using
method A. Since a significant amount of benzophenone was ob-
served in the chromatogram of the reaction mixture, the hydrolysis
of the imine group must contribute to the appearance of the color.
Consequently, the hydrolysis consumed the hydroxide and de-
creased the amount of the acidic imine analog. In addition, the
hydrolysis of 1 by TBAOH retarded the
a
-[11C]methylation of 3.
These types of hydrolyses were also observed in the reaction using
method B, and could be main reasons for the observed moderate
radiochemical conversion when TBAOH was used. In contrast to
TBAOH, the solution containing 3 gradually colored after mixing
with TBAF in DMSO. This significant factor suggested the slow gen-
In addition to the above mentioned points, there is another cru-
cial point when identifying a suitable base for the incorporation of
the [11C]methyl-group into alanine analogs. Due to the difficulties
R1
R2
O
*
R1
R2
O
O
*
[
11C]H3I +
N
H2N
N
OR3
OH
OR3
1
2
* = 11C
Scheme 1. General strategy for the synthesis of 2.

K. Kato et al. / Bioorg. Med. Chem. Lett. 21 (2011) 2437–2440
2439
(Scheme 2).15 The milder deprotection conditions for 6 enabled
the direct injection of the final reaction mixture containing 2 onto
the HPLC. Therefore, compound 5 was a more appropriate precur-
sor for the implementation of a remote-controlled synthesis proce-
dure for the preparation of 2.
Table 1
a
-[11C]Methylation of 3a
O
Ph
O
*
Ph
Ph
1 +
N
N
OBut
OBut
Ph
While PET tracer synthesis reactions require careful optimiza-
tion to ensure high yields, particular attention should also be paid
to the purification process in the development of an efficient PET
tracer synthesis protocol. AIB is a small polar molecule and is
therefore not an ideal substrate for HPLC purification using re-
versed-phase HPLC, which is the most frequently employed meth-
od in PET chemistry. The choice of a hydrophilic interaction
chromatography (HILIC) mode stationary phase with triazole
derivative coated silica provided a suitable method for the semi-
preparative HPLC purification of 2 using a mixture of MeCN and
ammonium acetate buffer.16 After implementation of the remote-
controlled system, the production of 2 was successfully achieved
in a total synthesis time of 30–35 min from the end of bombard-
ment (EOB). The syntheses could be carried out starting from
11.1 to 22.2 GBq of [11C]carbon dioxide (EOB). Final radiochemical
yields were in the range from 8% to 11% (decay uncorrected, re-
ferred to [11C]carbon dioxide).17 The amount of radioactivity was
sufficient to perform PET studies in animals.
* = 11C
3
4
Entry
Solvent
Base
Method
RCCb (%)
1
2
3
4
5
6
7
8
9
THF
THF
DMF
DMF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAOH
TBAOH
TEA
A
B
A
B
A
B
A
B
A
B
A
B
0
0
0
0
78.1 4.1
10.0 3.1
4.1 0.7
39.5 0.2
0
0
0
0
10
11
12
TEA
DBU
DBU
a
Each reaction was carried out more than three times.
The radiochemical conversion (RCC) was calculated by a radiochromatogram
b
using analytical HPLC following the decay correction.
The usefulness of our synthesis was demonstrated by a compar-
ison of PET studies using 2, [methyl-11C]methionine and [18F]FDG
for the same mouse bearing SY-tumor, a small cell lung cancer cell
line. The PET scans of 2 and [methyl-11C]methionine could be car-
ried out on the same day due to the short-lived carbon-11. As seen
in Figure 2, high uptake was observed in the tumors with all trac-
ers, but the maximum standardized uptake value (SUV max) of
compound 2 into tumor cells was higher than the one obtained
for [methyl-11C]methionine and [18F]FDG. This is the first compar-
ative tumor imaging study of these three molecules by PET and re-
sults strongly suggest the usefulness of 2 as a suitable radiotracer
for cancer diagnosis. Further details about the tumor imaging stud-
ies by PET will be reported separately.
eration of the anion of compound 3 which leaded to a poor radio-
chemical conversion when method B was used. Furthermore, the
color of the reaction mixture did not diminish significantly on
treatment of 1, 3 and TBAF in DMSO by method A until the
[
a-
11C]methylation reaction was quenched. Therefore, the hydrolysis
by TBAFÁ3H2O was negligible and the less latent activity of TBAF for
hydrolysis contributed to the furnishing of the anion, resulting in
high radiochemical conversion of 3.
The advantage of using TBAF is that it provided the opportunity
to render the synthesis of 2 more accessible. The lower latent
hydrolytic activity of TBAF permitted the a
-[11C]methylation reac-
tion of the methyl ester analog 5 without the presence of consider-
We have developed an efficient method for the synthesis of 2.
We found that the use of quaternary ammonium fluoride in DMSO
able hydrolysis-mediated side-reactions. The reaction of 1 and 5
a
-[11C]methylation of highly hindered analogs
with TBAF underwent the
a
-[11C]methylation using method A to
was useful for the
yield 6 with a 79.2 6.2% radiochemical conversion (decay-cor-
rected). In this reaction, prompt anion formation of 5 was observed
by the addition of TBAF, due to the reduced steric hindrance of the
methyl ester. The advantage of using 5 is the introduction of milder
reaction conditions for the subsequent deprotection steps. Conse-
quently, the hydrolysis of 6 was performed by the addition of a
using 1. The reaction conditions were not noticeably moisture
sensitive and did not require stringent stoichiometry. The estab-
lished method employed a stable labeling precursor, an expedient
11C-labeling agent and a one-pot approach, and therefore a remote-
controlled synthesis could be performed without any technical
difficulties. Comparative PET studies using 2 and some well known
radiotracers ([methyl-11C]methionine and
[
18F]FDG) could be
1 M NaOH aqueous solution (100
taining 6 and heating at 100 °C for 90 s. This was followed by cool-
ing and the addition of a 2 M HCl aqueous solution (150 L) at
room temperature for 90 s. radiochemical conversion of
lL) to the reaction mixture con-
successfully performed thanks to the reliability of the here
reported synthesis process. Future application of this radiotracer
might be thus revitalized due to the synthesis methodology
presented herein. We expect the synthesis of 2 can be accessible
where tumor imaging studies using 2 are useful. Furthermore,
we anticipate PET studies using 11C-labeled AIB will be revitalized
due to the synthesis methodology presented herein.
l
A
72.1 2.2% was obtained for the synthesis of compound 2 in three
steps (Scheme 2).15 In contrast, the addition of a 6 M HCl aqueous
solution to the reaction mixture containing 4 and heating at 120 °C
for 3 min gave 2 with a 70.0 3.3% conversion started from 3
a 1M NaOH
O
Ph
Ph
O
Ph
Ph
TBAF
DMSO
rt, 90s
100 °C, 90 s
2
1 +
1 +
N
N
OMe
OBut
b 2M HCl
rt, 90 s
OMe
OBut
*
5
6
6M HCl
O
Ph
Ph
O
Ph
Ph
TBAF
DMSO
rt, 90s
120 °C, 3 min
2
N
N
*
3
4
* = 11C
Scheme 2. Syntheses of 2.

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K. Kato et al. / Bioorg. Med. Chem. Lett. 21 (2011) 2437–2440
References and notes
1. Jager, P. L.; Vaalburg, W.; Pruim, J.; de Vries, E. G. E.; Langen, K.-J.; Piers, A. J.
Nucl. Med. 2001, 42, 432.
2. (a) McConathy, J.; Goodman, M. M. Cancer Metastasis Rev. 2008, 27, 555; (b)
Strauss, L. G. Eur. J. Nucl. Med. 1996, 23, 1409; (c) Whone, A. L.; Watts, R. L.;
Stoessl, J.; Davis, M.; Reske, S.; Nahmias, C.; Lang, A. E.; Rascol, O.; Ribeiro, M. J.;
Remy, P.; Poewe, W. H.; Hauser, R. A.; Brooks, D. J. Anal. Neurol. 2003, 54, 93.
3. McGivan, J. D.; Pastor-Anglada, M. Biochem. J. 1994, 299, 321.
4. (a) Schmall, B.; Conti, P. S.; Bigler, R. E.; Zanzonico, P. B.; Dahl, R. D.; Sundoro-
Wu, B. M.; Jacobsen, J. K.; Richard, L. Int. J. Nucl. Med. Biol. 1984, 11, 209; (b)
Oberdorfer, F.; Zobeley, A.; Weber, K.; Prenant, C.; Haberkorn, U.; Maier-Borst,
W. J. Labelled Compd. Radiopharm. 1992, 33, 345; (c) Prenant, C.; Theobald, A.;
Siegel, T.; Joachim, J.; Weber, K.; Haberkorn, U.; Oberdorfer, F. J. Labelled Compd.
Radiopharm. 1995, 36, 579; (d) Schmall, B.; Conti, P. S.; Alauddin, M. M. Nucl.
Med. Biol. 1996, 23, 263.
5. (a) Conti, P. S.; Sordillo, E. M.; Sordillo, P. P.; Schmall, B. Eur. J. Nucl. Med. 1985,
10, 45; (b) Bigler, R. E.; Zanzonico, P. B.; Schmall, B.; Conti, P. S.; Dahl, J. R.;
Rothman, L.; Sgouros, G.; MacEwen, E. G. Eur. J. Nucl. Med. 1985, 10, 48; (c)
Conti, P. S.; Sordillo, P. P.; Schmall, B.; Benua, R. S.; Bading, J. R.; Bigler, R. E.;
Laughlin, J. S. Eur. J. Nucl. Med. 1986, 12, 353; (d) Sordillo, P. P.; DiResta, G. R.;
Fissekis, J.; Conti, P.; Benua, R. S.; Yeh, S. D. J.; Laughlin, J. S. Am. J. Physiol.
Imaging 1991, 6, 171; (e) Schwarzbach, M.; Willeke, F.; Dimitrakopoulou-
Strauss, A.; Strauss, L. G.; Zhang, Y.-M.; Mechtersheimer, G.; Hinz, U.; Lehnert,
T.; Herfarth, C. Anticancer Res. 1999, 19, 1343.
6. (a) Någren, K.; Sutinen, E.; Jykkiö, S. J. Labelled Compd. Radiopharm. 2000, 43,
1013; (b) Suitinen, E.; Jyrkkiö, S.; Alanen, K.; Någren, K.; Minn, H. Eur. J. Nucl.
Med. 2003, 30, 72.
7. (a) McConathy, J.; Martarello, L.; Malveaux, E. J.; Camp, V. M.; Simpson, N. E.;
Simpson, C. P.; Bowers, G. D.; Olson, J. J.; Goodman, M. M. J. Med. Chem. 2002,
45, 2240; (b) Yu, W.; McConathy, J.; Williams, L.; Camp, V. M.; Malveaux, E. J.;
Zhang, Z.; Olson, J. J.; Goodman, M. M. J. Med. Chem. 2010, 53, 876.
8. (a) O’Donnell, M. J. Acc. Chem. Res. 2004, 37, 506; (b) Maruoka, K.; Ooi, T. Chem.
Rev. 2003, 103, 3013.
9. (a) O’Donnell, M. J.; Boniece, J. M.; Earp, S. E. Tetrahedron Lett. 1978, 30, 2641;
(b) EzQuerra, J.; Pedregal, C.; Moreno-Mañas, M.; Pleixats, R.; Roglans, A.
Tetrahedron Lett. 1993, 34, 8535; (c) Demark, S. E.; Stravenger, R. A.; Faucher, A.-
M.; Edwards, J. P. J. Org. Chem. 1997, 62, 3375.
10. Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.; Ito, M.; Soai, K. Science
2009, 324, 492.
11. (a) Miller, P. W.; Long, N. J.; Vilar, R.; Gee, A. D. Angew. Chem., Int. Ed. 2008, 47,
8998; (b) Långström, B.; Itsenko, O.; Rahman, O. J. Labelled Compd. Radiopharm.
2007, 50, 794.
12. (a) Clark, J. H. Chem. Rev. 1980, 80, 429; (b) Sun, H.; DiMagno, S. G. J. Am. Chem.
Soc. 2005, 127, 2050; (c) Xu, B.; Hammond, G. B. Angew. Chem., Int. Ed. 2008, 47,
689; (d) Kitagaki, S.; Teramoto, S.; Mukai, C. Org. Lett. 2007, 9, 2549; (e)
Okutani, M.; Mori, Y. J. Org. Chem. 2009, 74, 442.
13. (a) Adam, M. J.; Jivan, S.; Huser, J. M.; Lu, J. Radiochim. Acta 2000, 88, 207; (b)
Kato, K.; Zhang, M.-R.; Suzuki, K. Bioorg. Med. Chem. Lett. 2009, 19, 6222; (c)
Kato, K.; Kikuchi, T.; Nengaki, N.; Arai, T.; Zhang, M.-R. Tetrahedron Lett. 2010,
51, 5908.
Figure 2. Comparative PET images of 2, [methyl-11C]methionine, and [18F]FDG for a
tumor model mouse. Coronal (upper) and transaxial (lower) images of 2,
[methyl-11C]methionine (MET, center) and [18F]FDG (FDG, right) in a mouse bearing
small cell lung cancer SY-tumor cell lines. The same mouse was injected with
20 MBq of 2 or [methyl-11C]methionine, or 200 kBq of [18F]FDG intravenously, and a
PET scan was performed for 60 min just after injection. Shown are images at the
optimal time point of each PET tracer, 50–60 min for 2 and [18F]FDG and 15–25 min
for [methyl-11C]methionine. The arrowhead in each image indicates the SY tumor
location. The numbers at the bottom of the figure indicate the maximum SUV
within the tumor.
Acknowledgments
We thank the staff of the Cyclotron Operation and Radiochem-
istry sections for the production of radio isotopes and for the tech-
nical support in using these isotopes. We also thank Ms. Aya Sugyo
and Mr. Hidekatsu Wakizaka for their help with PET scanning.
14. Rabinovitz, M.; Cohen, Y.; Halpern, M. Angew. Chem., Int. Ed. 1986, 25, 960.
15. The radiochemical conversion was calculated from decay-corrected analytical
HPLC profiles.
Supplementary data
16. The conditions for HPLC use are described in the Supplementary data.
17. The isolated yield of 2 was determined for the calculated amount of [11C]O2
obtained by bombardment.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.bmcl.2011.02.065.