Synthesis of Fluroine-18 Labeled Imaging Agents
Mark M. Goodman, Ph.D.*, Nachwa Jarkas, Ph.D.,
Jiyoung Mun, Ph.D., Wone Seo, Ph.D.,
Jeffrey S. Stehouwer, Ph.D., Ronald J, Voll, Ph.D.,
Weiping Yu, Ph.D. and Fanxing Zeng, Ph.D.
.
Center For Systems Imaging
Emory University School of Medicine
Atlanta, Georgia, USA
Disclosures
• Nihon MediPhysics has licensed
Emory’s Amino Acid Technology
• Emory University is eligible for royalties
Radionuclidic and Chemical Properties Make
18F An Attractive Radioisotope for the
Development of Tracers for PET Imaging
• 110-min half-life
• Available in curie amounts as F- by 18O(p,n)18F with
low energy (12 MeV) cyclotrons
• One of the lowest energy β+ (0.635 MeV)
• Theoretical 1700 Ci per mmole high specific activity
• Metabolically stable carbon fluorine bond
Outline
• 1, ω-Alkanediol bis-(4-bromobenzenesulfonate)
• Serotonin Transporter Ligands
• 1,4-Ditosyloxy-but-2-ene
• Dopamine Transporter Ligands
• Cyclic Sulfamidates
• α,α,Dialkyl amino acids
• Pi-deficient Nitrogen Heterocycles
• Imidazo[1,2-b]pyridazines
1,ω-Dibrosyloxyalkanes and 1,4-Ditosyloxybut-2-ene As F-18 Precursors For Preparation
Monoamine Transporter Radioligands
K18F
O SO ( )
Br
Br
n OSO2
2
n = 2,3
Br
O2SO
( )
18
n
F
n = 2,3
K18F
O2SO
OSO2
O2SO
18
F
CNS monoamine transporters
• Monoamine transporters are critical for the
removal of dopamine, serotonin and
norepinephrine from the synaptic cleft
during neurotransmission
– NET: norepinephrine transporter
– SERT: serotonin transporter
– DAT: dopamine transporter
– each is a specific marker for monoaminergic neurons
Monoamine transporter function
Monoamine transporter blockade
Why develop imaging agents for
DAT, NET and SERT?
The dopaminergic, noradrenergic and serotonergic
systems are involved in the pathophysiology and/or
pharmacotherapy of many diseases and disorders
including:
–
–
–
–
–
ADHD
increased DAT density
PD
decreased DAT density
major depression
Alzheimer’s disease decreased NET and SERT density
Parkinson’s disease
Applications of DAT, NET and SERT
imaging agents
• Measure DAT, NET and SERT density in the
living brain
– DAT, NET and SERT density in controls vs study
population
– DAT, NET and SERT density before and after treatment
• Measure the occupancy of the DAT, NET and
SERT by psychoactive drugs
– in vivo competition for transporter binding
– useful for establishing the dosage, pharmacokinetics and
mechanism of action of drugs
The Incorporation Of Iodine On The Vinyl Substituent
At The 3’- and 4’-position Of The 3β-phenyl Ring
Leads To Potent And Selective SERT Ligands
H
N
CO2CH3
I
pZIENT
Ki (nM) SERT = 0.03, DAT = 3.5; NET = 15
H
N
CO2CH3
I
mZIENT
Ki (nM) SERT = 0.2; DAT = 30; NET = 102
MM. Goodman et al J Med Chem, 2003, 46: 925-935
JS. Stehouwer et al J Med Chem, 2006; 49:6760-6767.
PET and Images Of SERT In Human and
Non-Human Primates [11C]pZIENT and [11C]mZIENT
[11C]pZIENT
[11C]mZIENT
PET And Images Of SERT In Non-human Primates
With [123I]mZIENT
J Seibyl, G Tamagnan, JS Stehouwer, MM Goodman unpublished results
The Substitution Of Ethyl For Methyl At The
2β-Carboxylic Ester Of Cocaine Shows
No Increase In DAT Potency
CH3
N
CO2CH3
O
Cocaine
O
IC50 DAT=100 nM
CH3
N
CO2CH2CH3
O
O
IC50 DAT=130 nM
FI Carroll et al , 1992
The Incorporation Of Fluorine Onto The
2β-Carboxylic Ester Of pZIENT And mZIENT May
Lead To A Potent And Selective 18F-SERT Ligands
H
N
CO2(CH2)n18F
I
pZIENT
H
N
CO2(CH2)n18F
I
mZIENT
Synthesis of βFEpZIENT and βFPpZIENT
CH3
N
CO2CH3
I
a
1
CH3
N
CO2H
CH3CO CH (CH ) F
2
2
2 n
N
b
I
I
2
Boc
N
e,f
H
N
c,d
H
N
g,h
CO2CH2(CH2)nF
X
7 X = I; n = 1
8 X = I; n = 2
I
5,6
3,4
CO2CH2(CH2)nF
CO2CH2(CH2)nF
X
βFEpZIENT
βFPpZIENT
(10) X = I; n = 1
(11) X = I; n = 2
Reagents: (a) Dioxane /H2O; (b)POCl3, rt, 18h then FCH2(CH2)nOH, rt, 4h; (c) Troc-Cl, toluene, reflux, 2h: (d) Zn, AcOH, rt 24 h;
(e) (Boc)2O; (f) Z-(CH3)3SnCH=CHSn(CH3)3/Pd(Ph3P)4; (g) ICl; (h) TFA; then NH4OH
C Plisson et al., Journal of Medicinal Chemistry, 2007; 50:4553-4560.
Monoamine transporter competition assays
βFEpZIENT
βFPpZIENT
F
H
N
F
H
O
N
O
O
O
I
I
Compound
Ki for hSERT
Ki for hDAT
Ki for hNET
DAT/SERT
Log P7.4
pZIENT
0.05
3.5
24
69
1.5
βFEpZIENT
0.08
12
22
150
1.6
βFPpZIENT
0.08
27
25
338
1.6
All Ki values are reported in nanomolar (nM) units. The following radiotracers were
used: [3H]nisoxetine for NET, [125I]RTI-55 for DAT, [3H]citalopram for SERT
C Plisson et al., Journal of Medicinal Chemistry, 2007; 50:4553-4560
Radiosynthesis of [18F]βFEpZIENT and
[18F]βFPpZIENT
O2SO( )nOSO2
Br
Br
K18F
( ) 18F
O2SO
Br
n
n = 2,3
K222
n = 2,3
CH3CN, 110 C
70% RCY (EOB)
Boc
N
CO2H
e,f
Boc
N
CO2CH2(CH2)n18F
I
5
H
N
g,h
CO2CH2(CH2)n18F
I
6 n=1
7 n=2
I
[18F]βFEpZIENT
[18F]βFPpZIENT
Reagents: (e) TBAH,DMF; (f)18FCH2(CH2)nOBros; (g) TFA; (h) NH4OH
8 % decay corrected yield
40 mCi at end of synthesis
∼1 Ci/µmole at time of injection
(8) n = 1
(9) n = 2
Summed (0-240 min)MicroPET Images of
Cynomolgus Monkey Brain Following
[F-18]βFEpZIENT I.V. Administration
Time-activity curves from [18F]βFEpZIENT and
[18F]βFPpZIENT baseline studies show very high
SERT-rich to cerebellar ratios but slow kinetics
[18F]βFEpZIENT
[18F]βFPpZIENT
[F-18]β FEZIENT MicroPET Baseline
Study in Cynomolgus Monkey F4412 (4.7Kg)
[F-18]βFPZIENT MicroPET Baseline
Study in Cynomolgus Monkey F4412 (4.7Kg)
0.0018
0.0025
0.0016
MicroPET Counts
0.0015
0.001
Cere
Occip
Front
0.0005
Caud
Put
Thal
Midbrain
Pons
Medulla
Cere
Occip
Front
0.0014
MicroPET Counts
Caud
Put
Thal
Midbrain
Pons
Medulla
0.002
0.0012
0.001
0.0008
0.0006
0.0004
0.0002
0
0
0
50
100
150
Time (min)
200
250
0
50
100
150
Time (min)
200
250
Time-activity curves from [18F]βFEpZIENT
[18F]βFPpZIENT studies:citalopram chase
[18F]βFEpZIENT
[18F]βFPpZIENT
[F-18]βFPZIENT MicroPET
R,S-Citalopram (1.5 mg/Kg) Administered I.V.
at 120 min P.I. inCynomolgus Monkey F4412 (4.7Kg)
[F-18]βFEZIENT MicroPET
R,S-Citalopram (1.5 mg/Kg) Administered I.V.
at 120 min P.I. inCynomolgus Monkey F4412 (4.7Kg)
0.0018
0.0016
Caud
Put
0.002
Thal
Midbrain
0.0015
Pons
Medulla
0.001
Front
0.0005
Cere
Caud
Put
Thal
Midbrain
0.0014
MicroPET Counts
MicroPET Counts
0.0025
0.0012
0.001
Pons
Medulla
Cere
Occip
0.0008
0.0006
0.0004
Front
0.0002
0
0
50
100
150
Time (min)
200
250
0
0
40
80
120
Time (min)
160
200
240
The Design of βFEmZIENT and βFPmZIENT
Inspired By An SAR Study Of 3'-Analogs of
2-β-Carbomethoxy-3-β-(4'-iodophenyl)tropane
R
N
CO2CH3
Z
G Tamagnan et al., Bioorg. & Med. Chem. Lett. 2004, 14, 2117-2120.
Synthesis of βFEmZIENT and βFPmZIENT
N
O
O
O
N
OMe
OH
H2O
reflux
5
Br
6
H
N
N
1) Oxalyl
Chloride
O
O
2) F(CH2)nOH
7n=2
8n=3
Br
N
O(CH2)nF Me3Sn
9n=2
10 n = 3
Br
Br
N
O
SnMe3
Pd(PPh3)4, Ar(g),
Toluene, reflux
2) Zn dust,
AcOH, H2O
H
H
O
1) Troc-Cl
O(CH2)nF
O(CH2)nF
ICl
O
O(CH2)nF
I
SnMe3
11 n = 2
12 n = 3
1 n = 2, X = I
2 n = 3, X = I
JS Stehouwer et al., Journal of Medicinal Chemistry, in press.
Monoamine transporter competition assays
βFEmZIENT
βFPmZIENT
F
H
N
F
O
H
O
N
O
O
I
I
Compound
Ki for hSERT
Ki for hDAT
Ki for hNET
DAT/SERT
Log P7.4
mZIENT
0.2
30
102
150
1.4
βFEmZIENT
0.43
88
110
200
1.69
βFPmZIENT
0.26
180
68
691
1.64
All Ki values are reported in nanomolar (nM) units. The following radiotracers were
used: [3H]nisoxetine for NET, [125I]RTI-55 for DAT, [3H]citalopram for SERT
JS Stehouwer et al., Journal of Medicinal Chemistry, in press
Radiosynthesis of [18F]βFEmZIENT and
[18F]βFPmZIENT
Boc
H
N
O
OH
1) DMF, 0.1 M Bu4NOH(aq)
2) 18F(CH2)nOBs, 90 oC
3) 6 M HCl(aq), 90 oC
I 4) 6 M NH OH , 0 oC
4
(aq)
5) Semi-prep HPLC
13
18F
N
O
[18F]1 n = 2
O(CH2)n18F [18F]2 n = 3
I
FEBrosylate & 18F FPBrosylate 74% decay corrected yield
18F -1 and 18F -26 % decay corrected yield
∼1 Ci/µmole at time of injection
Time-activity curves from [18F]βFEmZIENT and
[18F]βFPmZIENT baseline studies
[18F]βFEmZIENT
[18F]βFPmZIENT
6
6
Caudate
5
Caudate
5
Putamen
Thalamus
Midbrain
Pons
3
Medulla
2
Cerebellum
Occipital
1
Thalamus
4
Midbrain
SUV
SUV
4
Putamen
3
Pons
Medulla
2
Cerebellum
1
Occipital
Frontal
Frontal
0
0
0
40
80
120 160
Time (min)
200
240
0
40
80
120
160
Time (min)
200
240
Time-activity curves from [18F]βFEmZIENT
[18F]βFPmZIENT studies:citalopram chase
[18F]βFEmZIENT
[18F]βFPmZIENT
3.5
5
4.5
Caudate
4
Putamen
3.5
Thalamus
Medulla
2
Cerebellum
1.5
SUV
SUV
Pons
2.5
Caudate
2.5
Putamen
Thalamus
Midbrain
3
3
2
Midbrain
1.5
Pons
Medulla
1
Occipital
1
Frontal
0.5
0
Cerebellum
0.5
Frontal
0
0
40
80
120 160
Time (min)
200
240
0
40
80
120 160
Time (min)
200
240
Summed (60-120 min)HRRT (2mm) PET Images of
an Awake Rhesus Monkey Brain Following
[F-18]βFEmZIENT I.V. Administration
Conclusions
• Nortropanes, βFEpZIENT, βFPpZIENT, βFEmZIENT and βFPmZIENT
were synthesized and showed high affinity for SERT with selectivity
of SERT over DAT and NET.
• The fluorine-18 labeled nortropanes showed in vivo high
regional brain uptake in agreement with the biodistribution of SERT.
•Fluorine-18 labeled βFEpZIENT showed the highest SERT rich tissue
To cerebellum ratios of 3.1 –to- 4.35.
•Fluorine-18 labeled βFEmZIENT showed the fastest kinetics.
• Fluorine-18 labeled βFEpZIENT and βFEmZIENT are undergoing
further validation as a SERT imaging agents in humans.
Analogs of MMG-142/IPT With Replacement of the (N-((E)-3-[123I]Iodopropen-1-yl) Group With a (N-((E)-4-[18F]-Fluorobut-2-en-1-yl)
Bioisostere Having Very Similar Imaging Properties and Labeled With
Fluorine-18 Would Be Excellent Candidate PET DAT Ligands.
18
123
F
I
N
N
CO2CH3
CO2CH3
Cl
MMG-142/IPT
Y
FBHNT
MM Goodman et al., Journal of Nuclear Medicine, 1992; 33: 890.
MM Goodman et al., Journal of Medicinal Chemistry, 1994; 37: 1535-1542.
HF Kung et al., Synapse, 1995; 20: 316-324.
The [123I]MMG-142 (IPT)-SPECT of one patient with sleep
behavior disorder (RBD), one patient with Parkinson's
disease (Hoehn and Yahr stage I) and one control subject
Eisensehr, I. et al. Brain 2000 123:1155-1160
Copyright restrictions may apply.
(E) & (Z) FBHNT Were Prepared From
(E) & (Z) 4- fluoro-1-tosyloxy-but-2-enes
TsO
OTs
OTs
TsO
Bu4NF
THF, reflux
Bu4NF
TsO
THF, reflux
TsO
N
CO2CH3
N
+
F
H
N
F
F
F
29%
38%
CO2CH3
X
KI, CH3CN
CO2CH3
70 C
(E)-FBHNT
X = H, F, Br, Cl, I
X
(Z)-FBHNT
80% X = Cl
X
P Chen et al., J Labelled Compd Radiopharm, 1999; 42: S400-402.
MM Goodman and P Chen, Fluoroalkenyl Nortropanes U.S. Patent 2002, USSN06/344,179 B1.
Competitive Binding Studies Showed The Most Potent and
Selective Analogues Resulted When (E)- and Y= H, Cl and F
18
N
F
CO2CH3
Y
Y
H
Br
I
(E)-Cl
F
(Z)-Cl
MMG/142,IPT
Altropane
DAT1, Ki (nM)
7.52
0.24
0.17
2.54
1.70
47.6
1.16
0.78
NET2, Ki (nM)
>10,000
91
57
>10,000
>10,000
>10,000
48.7
>10,000
1. [3H]WIN 35428 as reference for dopamine transporter site.
2. [3H]Nisoxetine for norepinephrine transporter site.
3. [3H]Citalopram for serotonin transporter site.
5-HTT3, Ki(nM)
102
0.85
0.21
24.2
85.5
>10,000
4.90
55.4
(E)-FBFNT and (E)-FBClNT Were Radiolabeled
Via (E) 4- [18F]fluoro-1-tosyloxy-but-2-ene
by a 2-step Reaction Sequence in 20% RCY
K[18F]F/K222
TsO
18
N
18
OTs
F
CH3CN, 85 C
TsO
+
100 C
CO2CH3
H
N
F
60-70% RCY
CO2CH3
CH3CN
X
X
18
[ F]FBHNT
X = F, Cl
P Chen et al., J Labelled Compd Radiopharm, 1999; 42: S400-402.
MM Goodman and P Chen, Fluoroalkenyl Nortropanes U.S. Patent 2002, USSN06/344,179 B1.
(E)-[18F]FBClNT and (E)-[18F]FBFNT Were
Evaluated in an Awake Rhesus Monkey:
(E)-[18F]FBFNT Reached Equilibrium at 20 min
2500
2500
2000
2000
1500
1500
nCi/mL
1000
nCi/mL
1000
500
500
0
0
0
60
120
0
60
Time (min)
Time (min)
18
N
120
18
F
N
CO2CH3
F
F
CO2CH3
Cl
(E)-[18F]FBFNT Was Evaluated in an Awake And
Anesthetized Macaque Monkey:
(E)- [18F]FBFNT Reached Equilibrium at 20 min
[18F]FBFNT into an anesthetized
cynomolgus monkey
[18F]FBFNT into an awake rhesus
monkey
Putamen-left
Putamen-right
Caudate-left
Caudate-right
S. Nigra
Thalamus
Cing. Gyrus
Amygdala
Cerebellum
Frontal Cortex
Occipital Cortex
Brainstem
Pons
Locus Ceruleus
Midbrain
0.12
Uptake (relative)
0.1
0.08
0.06
0.04
0.02
0
0
15
30
45
Time (min)
60
75
90
Caudate
Putamen
S. Nigra
Cerebellum
8
7
6
5
SUV
0.14
4
3
2
1
0
18
N
0
F
CO2CH3
F
20
40
60
80 100 120 140 160
Time (min)
HRRT PET images (summed 8-22 min) obtained by
injection of (E)-[18F]FBFNT into an awake rhesus monkey
(E)-[18F]FBClNT and (E)- [18F]FBBrNT Show
Undesirable Slow Kinetics
MicroPET TACs obtained by injection of
[18F]FBClNT into an anesthetized
cynomolgus monkey
Caudate
Putamen
S. Nigra
MicroPET TACs obtained by injection of
[18F]FBBrNT into an anesthetized
cynomolgus monkey
Caudate
Cerebellum
4
Putamen
S. Nigra
Cerebellum
5
3.5
4
3
SUV
SUV
2.5
2
3
2
1.5
1
1
0.5
0
0
0
40
80
120
160
Time (min)
200
0
40
80
120
160
Time (min)
200
18
18
F
240
F
N
O
N
O
OMe
OMe
Cl
Br
240
Conclusions
• Tropane FBFNT was synthesized and showed high affinity for DAT
with selectivity of DAT over SERT and NET.
• The fluorine-18 labeled FBFNT showed in vivo high
regional brain uptake in agreement with the biodistribution of DAT.
•Fluorine-18 labeled FBFNT is the only (N-((E)-4-[18F]-Fluorobut-2-en1-yl nortropane to show fast kinetics in vivo in primates.
Radiolabeled Amino Acids For
Tumor Imaging
• Amino acid transport is upregulated in many tumor
cells
• Certain amino acid transporters may play critical
roles in neoplastic cells
• The activity of specific amino acid transporters may
have prognostic and therapeutic implications
Amino acid transport
• 2 transport systems have been the major focus of amino
acid-based tumor imaging
System L (“leucine-preferring”)
System A (“alanine-preferring”)
L-leucine L-alanine
• Transport is generally more important than protein
synthesis in tumor imaging with amino acids
Fluorine-18 labeled analogues of AIB for tumor
imaging via system A transport
11
H2N
11
CO2H
CH3
HN CO2H
H2N
CO2H
18
11
[ C]α-amino
isobutyric acid (AIB)
N-[11C]Me-AIB
system A substrates
F
(R,S)-[18F]FAMP
CH3
HN CO2H
18
F
(R,S)-N-Me
[18F]FAMP
labeling of α,α-dialkyl amino acids
18F
Cyclic sulfamidate synthesis:
1) SOCl2, Et3N
1) pTsOH, EtOH
2) DMB-Cl, Et3N
OH
DMB
DMB NH CO2 tBu
Boc NH CO2 tBu
2) NaIO4, cat RuO2
OH
Radiolabeling:
DMB
O
N
O S
O
CO2 tBu
1) K[18F]F, K222, K2CO3
2) aqueous HCl
H2N
18
CO2H
F
[18F]FAMP
H3CO
OCH3
O
N
O S
O
CO2 tBu
~ 1 mg precursor
~70- 80% d.c. yield
70-80 minute synthesis
radiochemically pure
same procedure for
N-Me[18F]FAMP
DMB =
J McConathy et al, Journal of Medicinal Chemistry, 2002; 45: 2240-2249.
[18F]FAMP and [18F]N-MeFAMP Are Promising
Imaging Agents For The Detection of Intracranial
Neoplasms By PET
[18F]FAMP Tumor:Brain Ratio
26:1 (5 min), 36:1 (60 min) 37:1 (120 min)
Figure 2a. Comparison of activity in tumor tissue after
injection of [18F]FAMP(5a) and [18F]N -MeFAMP (5b).
[18F]N-MeFAMP Tumor:Brain Ratio
40:1 (5 min), 104:1 (60 min) 97:1 (120 min)
Figure 2b. Comparison of activity in normal brain after
2.5
0.07
FAMP
N-MeFAMP
percent dose per gram
percent dose per gram
3
2
1.5
1
0.5
0
5 min
60 min
120 min
Tissues compared at each time point by 2-tailed
t-test. No significant differences detected. Bars
indicate standard error.
0.06
FAMP
N-MeFAMP
*
*
0.05
0.04
0.03
*
0.02
*
0.01
0
5 min
60 min
120 min
Tissues compared at each time point by 2-tailed
t-test. * = p<0.03, ** = p<0.003. Bars indicate
standard error.
The Substitution of Fluorine-18 for Hydrogen at the
2-position of the Cyclopentane Ring May Lead to a
Leucine Type Amino Acid With High Tumor Uptake
H2N
COOH
11
COOH
NH2
18
[11C] ACPC
F
2-[18F]FACPC
Alzheimer’s disease and
β-Amyloid (Aβ) plaques
• Alzheimer’s disease (AD) is a progressive, ultimately fatal,
and neurodegenerative disorder.
• AD affects approximately 20 to 40% of the population
over 80 years of age.
• Aβ plaques and neurofibrillary tangles (stained
postmortem brain tissue) are the hallmark pathology.
• Aβ plaque probes are important for early diagnosis
and monitoring of the treatment of AD.
F-18 β-Amyloid Imaging Agents for PET
NC
18
F
CN
N
FDDNP (UCLA)
18
HO
N
S
F
H
N
18
N
CH3
F-18 PIB (Pittsburgh)
(
O
N
F-18 Strylpyridine (UPenn)
)
F
3
Introduction Of Nitrogens Into Benzene Enables Aromatic
Nucleophilic Substitution Directly On Heteroaromatic Ring
N
N
N
_
N
N
N
N
N
N
+
_
_
_
N
+
N
N
N
+
N
N
N
N
N
+
N
N
N
N
N
N
+
N
_N
N
_
+
+
N
N
N
N
N
+
N
N
N_
N
_
MM Goodman et al., Journal of Nuclear Medicine 1989;30:925.
Emory Nitrogen Heteroaromatic
Amyloid Ligands
CH3
H3C
18
F
N
N
N
N
N
[18F]7-M-6-FIPYRD
(FAME)
18
F
N
N
N
[18F]8-M-6-FIPYRD
Competition Assays
Ki (nM) vs [125I]- IMPY
Compound
IMPY
N
N
125
10.4
N
I
H3C
20
N
N(CH3)2
N
I
N
CH3
91.6
N
N(CH3)2
N
I
N
H3C
2.7
N
N(CH3)2
N
F
N
CH3
131.8
N
N(CH3)2
N
F
N
HO
S
NHCH3
PIB
7.8
N
Ki values were determined via the binding competition with [125I]IMPY
using human AD cortical tissues by autoradiography and homogenate.
Synthesis of Chloro-Precursor for
Radiolabeling [18F]7-M-6-FIPYRD
Cl
Cl
N
N
NH2
NH4. OH
130oC, 12h
Cl
N
N
71%
BrCH2
O
C
NH2
N
+
Cl
N
N
N
1. ethanol, reflux, 3h
2. NaHCO3, reflux, 5h
Cl
N
N
N
54%
Radiosynthesis of [18F]7-M-6-FIPYRD
N
Cl
N
N
N
K[18F]F-K222
DMSO
180 oC, 20 min
N
18
F
N
N
105 min from EOB
43% radiochemical yield
>99 % radiochemical purity
1.8-2.7 Ci /μmol specific activity at time of injection
N
[18F]7-M-6-FIPYRD Log P7.4 Compares Favorably
To Previously Reported Aβ Radioligands
Ligand
Log P7.4
[18F]7-M-6-FIPYRD
2.69
IMPY
3.58
6-OH BAT-1
2.0
[18F]7-M-6-FIPYRD Binding in AD
[18F]7-M-6-FIPYRD Also Differentiates
AD from Control Cases
AD
Normal
no plaques
Time-Activity Curves From
[18F]7-M-6-FIPYRD Study: Baseline
N
18
F
N
N
N
Collaborators
• PharmacologyClinton, D. Kilts, Ph.D., Tim Ely, Jon
McConathy, M.D., Ph.D.
• Biology Studies Gene Malveaux B.A., Mel Camp CNMT,
Laurent Martarello, Ph.D., Jon McConathy,
M.D., Ph.D.,
• Graphical AnalysisJohn R. Votaw, Ph.D.
Acknowledgments
NIMH
DOE
NMP