Synthesis, radiosynthesis, and biological evaluation of carbon-11 and fluorine-18 (N-fluoroalkyl) labeled 2β-carbomethoxy-3β-(4′-(3- furyl)phenyl)-tropanes and -nortropanes: Candidate radioligands for in vivo imaging of the serotonin transporter with posi

Article abstract of DOI:10.1021/jm0504095

2β-Carbomethoxy-3β-(4′-(3-furyl)phenyl)nortropane (1) was synthesized along with the N-methyl (2), N-fluoroethyl (3), N-fluoropropyl (4), and N-fluorobutyl (5) derivatives. The binding affinity for each compound to the human serotonin, dopamine, and norep

Full text of DOI:10.1021/jm0504095

7080
J. Med. Chem. 2005, 48, 7080-7083
Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and
Fluorine-18 (N-Fluoroalkyl) Labeled 2â-Carbomethoxy-3â-(4’-(3-furyl)phenyl)-
tropanes and -nortropanes: Candidate Radioligands for in Vivo Imaging of the
Serotonin Transporter with Positron Emission Tomography
Jeffrey S. Stehouwer,‡ Christophe Plisson,‡ Nachwa Jarkas,‡ Fanxing Zeng,‡ Ronald J. Voll,‡ Larry Williams,‡
Laurent Martarello,‡ John R. Votaw,‡ Gilles Tamagnan,§ and Mark M. Goodman*,‡
Department of Radiology, Emory University, 1364 Clifton Road NE, Atlanta, Georgia 30322, and Department of Psychiatry,
Yale University, West Haven Connecticut 06516
Received April 29, 2005
2â-Carbomethoxy-3â-(4′-(3-furyl)phenyl)nortropane (1) was synthesized along with the N-methyl
(2), N-fluoroethyl (3), N-fluoropropyl (4), and N-fluorobutyl (5) derivatives. The binding affinity
for each compound to the human serotonin, dopamine, and norepinephrine transporters was
determined using transfected HEK-293 cells. Radiolabeling and microPET brain imaging studies
were performed with [11C]1, [11C]2, and [18F]3 to determine their utility as in vivo imaging
agents.
Introduction
Chemistry
p-Bromophenylnortropane 69 (Scheme 1) was coupled
to 3-(tri-n-butylstannyl)furan (7)14 to give 1. Hydrolysis
of 1 in refluxing 1,4-dioxane/H2O15 afforded nortropane
acid 8 (the X-ray crystal structure of zwitterionic 8 is
reported in the Supporting Information), which was
N-Boc protected to give the radiolabeling precursor 9.
Reaction of 1 with the appropriate bromofluoroalkane
afforded the N-(ω-fluoroalkyl)nortropanes 3-5. p-Bro-
mophenyltropane 109 was coupled to 7 to give 2, which
was hydrolyzed in refluxing 1,4-dioxane/H2O to afford
the radiolabeling precursor 11.
Investigations into the neurochemical mechanism of
cocaine addiction revealed that cocaine binds to the
serotonin transporter (SERT), the dopamine transporter
(DAT), and the norepinephrine transporter (NET).1
Efforts to develop cocaine antagonists resulted in the
synthesis of numerous tropane derivatives with varying
affinities for these monoamine transporters.2,3 These
efforts revealed that SERT affinity and selectivity could
be enhanced by N-demethylation to give a nortropane
analogue and by alkylation of the 4′-position of the 3â-
phenyl ring.4-6 Further exploration indicated that un-
saturated substituents in the 3â-phenyl ring (4′-
position) increased SERT potency of the ligand.7,8
As part of ongoing research in our laboratories to
develop SERT-specific tropane and nortropane positron
emission tomography (PET) and single photon emission
computerized tomography (SPECT) imaging agents,9 we
have been exploring the incorporation of unsaturated
groups or heterocycles in the 4′-position of the 3â-phenyl
ring. We report here the synthesis and biological evalu-
ation of 2â-carbomethoxy-3â-(4′-(3-furyl)phenyl)nortro-
pane (3FPNT, 1)10 and 2â-carbomethoxy-3â-(4′-(3-furyl)-
phenyl)tropane (3FPT, 2) and the radiolabeling and
evaluation of [11C]1 and [11C]2 as in vivo microPET
imaging agents for the SERT. Additionally, we have
explored whether the selectivity of SERT vs DAT
binding can be enhanced by incorporation of N-(ω-
fluoroalkyl) groups.5,11 To this end we synthesized the
N-fluoroethyl (3), N-fluoropropyl (4), and N-fluorobutyl
(5) derivatives of 1 and explored the microPET imaging
properties of [18F]3. Recently, the synthesis and mono-
amine transporter affinity have been reported for 2â-
carbomethoxy-3â-(3′-(2-furyl)phenyl)tropane12 and 2â-
carbomethoxy-3â-[4′-(substituted thiophenyl)]phenyl-
tropanes.13
Radiochemistry
The radiosynthesis of [11C]1 is shown in Scheme S1
in the Supporting Information. 3FPNT N-Boc acid 9 was
deprotonated with 0.1 M Bu4NOH(aq) and O-methylated
with 11CH3I. The Boc group was cleaved under acidic
conditions, the reaction mixture was neutralized, and
[11C]1 was purified by HPLC. The HPLC fractions
containing [11C]1 were combined, and the product was
isolated by solid-phase extraction according to a previ-
ously reported procedure.16 The octanol/water partition
coefficient of [11C]1 was measured according to a known
procedure17 and found to be log P7.4 ) 1.25. The radio-
synthesis of [11C]2a was accomplished through O-
methylation of 11 as shown in Scheme S2. The radio-
synthesis of [11C]2b was accomplished through N-meth-
ylation of 1 as shown in Scheme S3. The radiosynthesis
of [18F]3 was achieved by N-alkylation of 1 with [18F]-
fluoroethyl brosylate (Scheme S4). The octanol/water
partition coefficient of [18F]3 was determined to be
log P7.4 ) 2.27.
In Vitro Competition Assays
Tropanes 1 and 2 and 3-5 were screened for binding
to human monoamine transporters using in vitro com-
petition binding assays in HEK-293 cells stably express-
ing the transfected human SERT, DAT, or NET accord-
* To whom correspondence should be addressed. Phone: (404) 727-
9366. Fax: (404) 727-3488. E-mail: mgoodma@emory.edu.
‡ Emory University.
§ Yale University.
10.1021/jm0504095 CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/04/2005

Brief Articles
Journal of Medicinal Chemistry, 2005, Vol. 48, No. 22 7081
Scheme 1
Table 1. Results of in Vitro Competition Binding Assays with
with peak uptake achieved after 85-95 min. Compari-
son of the uptake in these regions to cerebellum18 (Cer)
uptake after 95 min afforded the following ratios: P/Cer
) 2.68, MB/Cer ) 2.64, C/Cer ) 2.47, Med/Cer ) 2.20,
T/Cer ) 2.01. These ratios reflect the known distribution
of SERT in the brain. Figure S4 shows the time-activity
curves for a study where the SERT binding sites were
preblocked by injection with the SERT selective ligand
(R,S)-citalopram‚HBr (1.5 mg/kg) 30 min prior to the
injection of [11C]1. As shown by these results, significant
uptake of [11C]1 is only observed in the caudate and
putamen, indicating that when the SERT sites are
blocked, [11C]1 will bind to another site, presumably the
DAT. This would be expected on the basis of the binding
affinities reported in Table 1. Figure S5 shows the
time-activity curves for a chase study where the DAT
selective ligand RTI-177 (0.3 mg/kg) was administered
60 min after injection of [11C]1. There is a similar uptake
of [11C]1 in the caudate and putamen in this study, as
was observed in the baseline study in Figure S3, and
this uptake is not displaced by RTI-177, suggesting that
[11C]1 is primarily bound to the SERT in these studies.
Figure S6 shows the time-activity curves for a chase
study using the NET selective ligand reboxetine (1.5 mg/
kg) at 60 min after injection of [11C]1. Injection of
reboxetine failed to displace [11C]1, further indicating
that uptake in the brain is a result of preferential
binding to the SERT.
Imaging studies were also performed with [18F]3 to
take advantage of the longer half-life of 18F (109.8 min).
Although the data in Table 1 indicate that 3 has a lower
affinity for the SERT than 4 or 5, 3 has a higher
selectivity for the SERT over the DAT than 4 or 5.
Figure S7 shows the time-activity curves for a baseline
study with [18F]3 in a cynomolgus monkey. This study
shows that [18F]3 has good kinetics, but the high uptake
observed suggests that [18F]3 is binding to the DAT and
the SERT in the putamen and caudate. This was
verified by performing a chase study with the DAT
selective ligand RTI-113 (Figure S8), which resulted in
a nearly complete displacement of [18F]3 from the
putamen and caudate. Therefore, no further imaging
studies were performed with [18F]3.
Human Monoamine Transporters
Ki (nM)a
SERT selectivity
compd
SERT
DAT
NET
DAT/SERT NET/SERT
1
2
3
4
5
0.11 ( 0.01 4.30 ( 0.95 4.52b
39.1
8.7
11.7
6.8
41.1
353.1
1081.6
3185.9
2382.9
0.25 ( 0.03 2.18 ( 0.39 88.28b
0.49 ( 0.06 5.99 ( 0.11 551.60b
0.46 ( 0.00 3.12 ( 0.11 1465.50 ( 82.73
0.31 ( 0.05 2.12 ( 0.07 667.20 ( 151.60
7.6
a n ) 2. b n ) 1.
ing to a previously reported procedure.9 The binding
affinities for each transporter were determined using
[3H]citalopram (SERT), [125I]RTI-55 (DAT), or [3H]-
nisoxetine (NET). The data in Table 1 indicate that 1
has a higher affinity for the SERT as expected for a
nortropane compared to it’s tropane analogue 2.4 Fur-
thermore, 1 is ∼40 times more selective for the SERT
than the DAT or NET, whereas 2 is less than 9 times
as selective for the SERT over the DAT. The data in
Table 1 also indicate that incorporation of an N-(ω-
fluoroalkyl) group does not result in an increased
affinity of the ligand for the SERT compared to 2 nor
does this improve selectivity for the SERT over the DAT.
In Vivo Nonhuman Primate Imaging
The in vivo regional brain uptake of [11C]1, [11C]2, and
[18F]3 was determined in anesthetized rhesus and
cynomolgus monkeys using a Concorde microPET P4
instrument according to a previously reported proce-
dure.9 Baseline studies were initially performed to
determine the extent of uptake of [11C]1, [11C]2, and
[18F]3 in the SERT-rich regions of the brain. Figures
S1 and S2 (Supporting Information) show the time-
activity curves for the brain regions of cynomolgus
monkeys after injection of [11C]2a and [11C]2b, respec-
tively. The data in Figure S1 indicate that the uptake
of [11C]2a in the putamen and caudate increases con-
tinuously throughout the course of the study without
reaching equilibrium. A similar result is observed after
the injection of [11C]2b (Figure S2). This is attributed
to the binding of [11C]2 primarily to the DAT rather than
the SERT as a result of the significantly greater
concentration of DAT than SERT in these brain regions.
Therefore, no further imaging studies were performed
with [11C]2.
Conclusions
Figure S3 shows the time-activity curves obtained
after injection of [11C]1 into a cynomolgus monkey. The
data indicate a high uptake in the caudate (C), putamen
(P), thalamus (T), midbrain (MB), and medulla (Med)
A 3-furyl ring was incorporated into the 4-position of
the phenyl ring of a 3â-tropane to give the nortropane
1, the tropane 2, and the N-(ω-fluoroalkyl) derivatives
3-5. In vitro competition binding assays with human

7082 Journal of Medicinal Chemistry, 2005, Vol. 48, No. 22
Brief Articles
Hz), 2.23, (s, 3 H), 2.21 (m, 1 H), 2.11 (m, 1 H), 1.72 (m, 2 H),
1.62 (m, 1 H). HRMS (EI) Calcd for C20H23NO3: 325.1678.
Found: 325.1682. Anal. Calcd for C20H23NO3: C, 73.82; H,
7.12; N, 4.30; O, 14.75. Found: C, 72.65; H, 7.13; N, 4.26; O,
14.29.
monoamine transporters indicated that 1 had the high-
est affinity for the SERT of all the compounds tested,
but 1 also showed a modest affinity for the DAT and
NET. N-Alkylation reduced the SERT affinity of 2-5
relative to 1 and increased the DAT affinity of 2, 4, and
5 relative to 1. In vivo microPET brain imaging studies
in anesthetized monkeys with [11C]1 showed a high
uptake of [11C]1 in the SERT-rich regions of the brain,
but blocking and chase studies revealed that some
binding to the DAT may also be involved. MicroPET
studies with [11C]2 and [18F]3 demonstrated that N-
alkylation results in a preferential shift to DAT binding
of these compounds in the caudate and putamen. Taken
together, these results indicate that incorporation of a
3-furyl ring into the 4-position of the phenyl ring of a
3â-tropane or nortropane does not significantly enhance
the selectivity for the SERT over the DAT or NET, and
therefore, any further PET imaging studies to translate
a candidate from this series to human use are not
warranted.
N-(2-Fluoroethyl)-2â-carbomethoxy-3â-(4′-(3-furyl)phen-
yl)nortropane (3). 3FPNT 1 (24 mg, 7.71 × 10-5 mol),
1-bromo-2-fluoroethane (70 µL, 0.94 mmol, 12.2 equiv), NEt3
(13 µL, 9.3 × 10-5 mol, 1.2 equiv), and CHCl3 (5 mL) were
stirred at reflux under Ar for 23 h. The solvent was removed
to give a brown residue that was purified by preparative TLC
(75:20:5 v/v/v hexane/EtOAc/NEt3 × 2) to afford 8 mg (29%)
of a white solid: TLC Rf ) 0.28 (75:20:5 v/v/v hexane/EtOAc/
1
NEt3); H NMR (600 MHz, CDCl3) δ 7.69 (br d, 1 H, J ) 0.6
Hz), 7.45 (br dd, 1 H, J ) 1.8 Hz), 7.40 (d, 2 H, J ) 7.8 Hz),
7.27 (d, 2 H, J ) 7.8 Hz), 6.67 (br d, 1 H, J ) 0.6 Hz), 4.51 +
4.43 and 4.47 + 4.39 (4 m, 2 H, 2JHF ) 47.4 and 48.0 Hz), 3.79
(m, 1 H), 3.52 (s, 3 H), 3.45 (m, 1 H), 3.03 (m, 1 H), 2.95 (t, 1
H, J ) 4.2 Hz), 2.62 (m, 3 H), 2.14 (m, 1 H), 2.02 (m, 1 H),
1.79 (m, 1 H), 1.70 (m, 2 H); 13C NMR (150 MHz, CDCl3) δ
172.16, 143.70, 142.11, 138.44, 130.09, 127.96, 126.54, 125.65,
1
109.07, 84.14 (d, JCF ) 165.0 Hz), 63.81, 62.59, 53.90 (d, JCF
) 20.7 Hz), 52.90, 51.26, 34.18, 34.00, 26.43, 25.94. HRMS (EI)
Calcd for C21H24O3NF: 357.1740. Found: 357.1750. Anal.
Calcd for C21H24O3NF: C, 70.57; H, 6.77; N, 3.92; O, 13.43.
Found: C, 67.84; H, 6.70; N, 3.94; O, 15.16.
Experimental Section
2â-Carbomethoxy-3â-(4′-(3-furyl)phenyl)nortropane
(3FPNT, 1). 3â-(4′-Bromophenyl)nortropane (6) (100 mg, 3.08
× 10-4 mol), 3-(tri-n-butylstannyl)furan (7) (456 mg, 1.28
mmol, 4.2 equiv), palladium(tetrakis(triphenylphosphine)) (36
mg, 3.12 × 10-5 mol, 0.1 equiv), and Ar-purged toluene (15
mL) were stirred at reflux under Ar for 16.5 h, cooled, and
poured onto a dry silica plug (43 mm height × 43 mm i.d.).
The product was eluted under vacuum with CHCl3 (75 mL),
hexane/EtOAc/NEt3 75:20:5 (200 mL), 50:45:5 (200 mL), 30:
70:5 (400 mL) v/v/v, and then 5% NEt3/EtOAc. The solvent
was removed to give a yellow oil that was further purified by
radial chromatography (1 mm silica, hexane/EtOAc/NEt3 75:
20:5 (300 mL) and then 50:45:5 v/v/v). The solvent was
removed to give a colorless oil that was dried under vacuum
to afford 62 mg (65%) of a white solid. Samples for binding
assays and elemental analysis were further purified by
preparative thin-layer chromatography (TLC). TLC Rf ) 0.08
(50:45:5 v/v/v hexane/EtOAc/NEt3), Rf ) 0.33 (85:10:5 v/v/v
CHCl3/EtOAc/NEt3); 1H NMR (400 MHz, CDCl3) δ 7.71 (dd, 1
H, J ) 1.2 Hz), 7.47 (dd, 1 H, J ) 2.0 and 1.6 Hz), 7.41 (d, 2
H, J ) 8.4 Hz), 7.20 (d, 2 H, J ) 8.4 Hz), 6.68 (dd, 1 H, J ) 1.2
and 0.8 Hz), 3.76 (m, 1 H), 3.72 (m, 1 H), 3.39 (s, 3 H), 3.26
(dt, 1 H, J ) 5.9 Hz, J ) 12.8 Hz), 2.76 (m, 1 H), 2.44 (td, 1 H,
J ) 2.9 Hz, J ) 12.9 Hz), 2.19-1.97 (m, 3 H), 1.82-1.63 (m,
3 H); 13C NMR (100 MHz, CDCl3) δ 174.02, 143.74, 141.19,
138.46, 130.70, 127.90, 126.26, 125.82, 108.88, 56.43, 53.76,
51.31, 51.22, 35.55, 33.80, 29.18, 27.76. HRMS (EI) Calcd for
C19H21NO3: 311.1521. Found: 311.1524. Anal. Calcd for
C19H21NO3: C, 73.29; H, 6.80; N, 4.50; O, 15.41. Found: C,
70.07; H, 6.70; N, 4.34; O, 15.57. HPLC: tR ) 4.8 min (Waters
Nova-Pak C18 3.9 mm × 150 mm, 75:25:0.1 v/v/v MeOH/H2O/
NEt3, 1 mL/min), 96% purity by HPLC for sample used for
binding assay and elemental analysis.
2â-Carbomethoxy-3â-(4’-(3-furyl)phenyl)tropane (3FPT,
2). 3â-(4′-Bromophenyl)tropane (10) (102 mg, 3.02 × 10-4 mol),
3-(tri-n-butylstannyl)furan (7) (856 mg, 2.40 mmol, 7.9 equiv),
palladium(tetrakis(triphenylphosphine)) (36 mg, 3.12 × 10-5
mol, 0.1 equiv), and Ar-purged toluene (15 mL) were stirred
at reflux under Ar for 17 h, cooled, and poured onto a dry silica
plug (43 mm height × 43 mm i.d.). The product was eluted
under vacuum with CHCl3 (75 mL) and then 75:20:5 v/v/v
hexane/EtOAc/NEt3 to give an off-white solid that was further
purified by radial chromatography (2 mm silica, 90:8:2 v/v/v
hexane/EtOAc/NEt3) to afford 40 mg (41%) of a white solid:
1H NMR (600 MHz, CDCl3) δ 7.68 (s, 1 H), 7.45 (dd, 1 H, J )
1.2 Hz, J ) 1.8 Hz), 7.39 (d, 2 H, J ) 8.1 Hz), 7.26 (d, 2 H, J
) 8.1 Hz), 6.67 (m, 1 H), 3.57 (m, 1 H), 3.50 (s, 3 H), 3.38 (m,
1 H), 3.01 (dt, 1 H, J ) 5.4 Hz, J ) 13.2 Hz), 2.92 (br dd, 1 H,
J ) 3.6 Hz, J ) 4.2 Hz), 2.61 (td, 1 H, J ) 2.4 Hz, J ) 12.6
N-(3-Fluoropropyl)-2â-carbomethoxy-3â-(4′-(3-furyl)-
phenyl)nortropane (4). 3FPNT 1 (29 mg, 9.31 × 10-5 mol),
1-bromo-3-fluoropropane (0.1 mL, 1.1 mmol, 11.7 equiv), NEt3
(16 µL, 0.11 mmol, 1.2 equiv), and CHCl3 (5 mL) were stirred
at reflux under Ar for 16 h. The solvent was removed to give
a brown residue that was purified by preparative TLC (75:
20:5 v/v/v hexane/EtOAc/NEt3) to give 22 mg (64%) of a white
1
solid: TLC Rf ) 0.31 (75:20:5 v/v/v hexane/EtOAc/NEt3); H
NMR (600 MHz, CDCl3) δ 7.69 (s, 1 H), 7.45 (dd, 1 H, J ) 1.8
Hz), 7.39 (d, 2 H, J ) 7.8 Hz), 7.26 (d, 2 H, J ) 7.8 Hz), 6.67
3
(dd, 1 H, J ) 0.6 and 1.2 Hz), 4.53 (dt, 2 H, JHH ) 6.0 Hz,
2JHF ) 47.4 Hz), 3.69 (m, 1 H), 3.49 (s, 3 H), 3.41 (m, 1 H),
3.03 (dt, 1 H, J ) 5.4 Hz, J ) 12.6 Hz), 2.94 (t, 1 H, J ) 3.9
Hz), 2.60 (td, 1 H, J ) 3.0 Hz, J ) 12.0 Hz), 2.39 (m, 2 H),
2.10 (m, 1 H), 2.02 (m, 1 H), 1.82-1.62 (3 m, 5 H); 13C NMR
(150 MHz, CDCl3) δ 172.16, 143.68, 142.21, 138.43, 130.05,
1
127.95, 126.53, 125.62, 109.06, 82.49 (d, JCF ) 163.1 Hz),
63.38, 61.73, 52.99, 51.14, 49.47, 34.20, 34.15, 30.24 (d, JCF
)
18.6 Hz), 26.23, 26.14. HRMS (EI) Calcd for C22H26O3NF:
371.1897. Found: 371.1882. Anal. Calcd for C22H26O3NF: C,
71.14; H, 7.06; N, 3.77, O, 12.92. Found: C, 69.42; H, 7.11; N,
3.63; O, 12.22.
N-(4-Fluorobutyl)-2â-carbomethoxy-3â-(4′-(3-furyl)phen-
yl)nortropane (5). 3FPNT 1 (27 mg, 8.67 × 10-5 mol),
1-bromo-4-fluorobutane (0.1 mL, 0.93 mmol, 10.7 equiv), NEt3
(15 mL, 0.11 mmol, 1.2 equiv), and CHCl3 (5 mL) were stirred
at reflux under Ar for 16 h. The solvent was removed to give
a brown residue that was purified by preparative TLC (75:
20:5 v/v/v hexane/EtOAc/NEt3) to afford 23 mg (69%) of a white
1
solid: TLC Rf ) 0.32 (75:20:5 v/v/v hexane/EtOAc/NEt3); H
NMR (600 MHz, CDCl3) δ 7.69 (s, 1 H), 7.45 (s, 1 H), 7.39 (d,
2 H, J ) 8.4 Hz), 7.27 (d, 2 H, J ) 8.4 Hz), 6.67 (s, 1 H), 4.45
(dt, 2 H, 3JHH ) 6.0 Hz, 2JHF ) 47.4 Hz), 3.69 (m, 1 H), 3.48 (s,
3 H), 3.40 (m, 1 H), 3.03 (dt, 1 H, J ) 5.4 Hz, J ) 13.2 Hz),
2.94 (m, 1 H), 2.60 (td, 1 H, J ) 1.8 Hz, J ) 12.3 Hz), 2.29 (m,
2 H), 2.10 (m, 1 H), 2.00 (m, 1 H), 1.80-1.68 (m, 4 H), 1.63
(m, 1 H), 1.47 (m, 2 H); 13C NMR (150 MHz, CDCl3) δ 172.25,
143.68, 142.31, 138.43, 130.04, 127.97, 126.54, 125.62, 109.07,
1
84.39 (d, JCF ) 163.9 Hz), 63.12, 61.67, 53.19, 53.06, 51.16,
34.24, 28.34, 28.22, 26.21, 26.16, 24.85. HRMS (EI) Calcd for
C23H28O3NF: 385.2053 Found: 385.2052. Anal. Calcd for
C23H28O3NF: C, 71.66; H, 7.32; N, 3.63; O, 12.45. Found: C,
69.96; H, 7.26; N, 3.53; O, 12.80.
Acknowledgment. This work was funded by NIMH.
We thank Dr. Kenneth I. Hardcastle, Department of
Chemistry, Emory University, for solving the crystal
structure of zwitterionic 8. We acknowledge the use of

Brief Articles
Journal of Medicinal Chemistry, 2005, Vol. 48, No. 22 7083
ethenyl)phenyl]tropanes: Candidate Radioligands for in Vivo
Imaging of the Serotonin Transporter. J. Med. Chem. 2004, 47,
1122-1135.
shared instrumentation provided by grants from the
NIH and the NSF.
(10) Stehouwer, J. S.; Jarkas, N.; Plisson, C.; Voll, R. J.; Votaw, J.
R.; Williams, L. A.; Tamagnan, G. D.; Goodman, M. M. MicroPET
Imaging of the Brain Serotonin Transporter (SERT) in Non-
Human Primates with [11C]3FPNT. J. Nucl. Med. 2004, 45
(Abstract Book Supplement, 439P, No. 1369).
Supporting Information Available: MicroPET imaging
time-activity curves, radiolabeling schemes, experimental
details, X-ray crystal structure of zwitterionic 8, crystal
packing analysis, and X-ray crystallographic experimental and
data tables. This material is available free of charge via the
Internet at http://pubs.acs.org.
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