[18F]-Fluoride capture and release: azeotropic drying free nucleophilic aromatic radiofluorination assisted by a phosphonium borane

Article abstract of DOI:10.1039/c6cc05168e

[¹⁸F]-Fluoride ready for aromatic nucleophilic substitution was prepared according to a simple process including trapping of aqueous [¹⁸F]-fluoride on a cartridge pre-loaded with the phosphonium borane [(Ph₂MeP)C₆H₄(BMes₂)]⁺, then releasing by elution of TBACN in dry acetonitrile. Subsequent radiofluorination was successfully applied to a model reaction and to the radiosynthesis of [¹⁸F]-setoperone.

Full text of DOI:10.1039/c6cc05168e

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: C. Perrio, S.
Schmitt, D. Pla, F. P. Gabbaï, K. Chansaenpak, B. Mestre-Voegtlé and E. gras, Chem. Commun., 2016,
DOI: 10.1039/C6CC05168E.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 4
View Article Online
DOI: 10.1039/C6CC05168E
Journal Name
COMMUNICATION
[18F]-Fluoride Capture and Release: azeotropic drying free
nucleophilic aromatic radiofluorination assisted by
Phosphonium Borane.
a
Received 00th January 20xx,
Accepted 00th January 20xx
C. Perrio,a,b,c,* S. Schmitt,a,b,c D. Pla,d F.P. Gabbaï,e K. Chansaenpak,e B. Mestre-Voegtle,d E. Gras.d,*
DOI: 10.1039/x0xx00000x
www.rsc.org/
[
18F]-Fluoride ready for aromatic nucleophilic substitution was been proposed in order to avoid the azeotropic drying step,
prepared according to a simple process including trapping of such as modified cartridges (resin-bound pyridinium supports,5
cyclotron-produced aqueous [18F]-fluoride on a cartridge pre- supports preloaded with quaternary ammonium salts6) or
loaded with the phosphonium borane (Ph2MeP)C6H4(BMes2)]+, various [18F]-fluoride elution protocols (involving strong
then releasing by elution of TBACN in dry acetonitrile. Subsequent organic phosphazene bases,4 conventional phase transfer
radiofluorination was successfully applied to a model reaction and catalysts,7 or a combination of K222 and KH2PO4 in t-butanol8).
to the radiosynthesis of [18F]-setoperone.
Main group elements have brought high innovation in the
design of prosthetic group for radiolabelling biomolecules.9
We envisioned their application towards the preparation of
dry [18F]-fluoride and subsequent aromatic radiofluorination.
Indeed, cationic boranes of general structure 1+ are known to
bind fluoride ions in water and yield corresponding
zwitterionic fluoroborates.10 This has led to the development
of fluoride sensors. The use of a sulfonium borane has also
been applied for the capture of aqueous fluoride and its
release in an organic solvent.11 In this case, fluoride release is
triggered by removal of the positive charge of the sulfonium
moiety in 2-F as illustrated in scheme 1.
Fluorine-18 possesses highly favorable decay properties
(96.9% β+, Eβ
= 635 keV, t1/2 = 109.7 min) for in vivo
max
+
imaging purposes by positron emission tomography, and is
frequently used for the development of radiopharmaceuticals
for preclinical and clinical studies.1 Most of the 18F-
radiolabeling approaches use [18F]-fluoride anion as
radioactive source due to its efficient production with high
experimental specific activities according to the nuclear
18O(p,n)18F reaction. Proton irradiation of [18O]-H2O leads to
[18F]-fluoride in aqueous solution. Thus, the syntheses of 18F-
labeled tracers typically require the preparation of reactive,
“dried”, [18F]-fluoride before radiolabelling can take place.
Classically, [18F]-fluoride is trapped on an anion exchange
cartridge,2 allowing the removal and recovery of [18O]-water,
and then eluted using a mixture of water and acetonitrile
containing a base (K2CO3) and a cryptand (Kryptofix, K222).
Water is finally removed by repeated azeotropic drying under
heating, reduced pressure and concomitant gas supply,
providing the [18F]-fluoride starting material. Although
optimized, this process hardly controls the precise hydration
state of the fluoride,3 lengthens the process while radioactive
decay takes place and favours adsorption of [18F]-fluoride on
the surface of the reactor.4 Thus alternative approaches have
Scheme 1: Cationic boranes and thiolate induced nucleophilic fluorination
Furthermore, the affinity of cationic boranes for cyanide has
also been exemplified by modulation of their intrinsic
properties. Thus [(Me3N)C6H4(BMes2)]+ displays a much higher
affinity for cyanide than fluoride anions. Moreover,
displacement and release of fluoride from [Mes2PhBF]- with
cyanide anions have been efficiently carried out.12 Based on
the proven utility of this fluoride capture/release strategy for
the formation of C–F bonds, we reckoned that applying this
concept would be particularly appropriate in [18F]-fluoride
chemistry. Thus, implementation of robust strategies for
production of [18F]-fluoride starting material in a reproducible
fashion represents a huge breakthrough to overcome the
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-4 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 4
View Article Online
DOI: 10.1039/C6CC05168E
COMMUNICATION
Journal Name
limitations of conventional methods based on fuzzy azeotropic conclusive in our first essay based on previous reports on the
water removal. As a proof of concept, we report here a simple generation of dry TBAF (see supp. Info for 11B and 19F time
two steps sequence consisting in an aqueous [18F]-fluoride course experiments).18 But we then observed that upon
(
capture with phosphonium borane (Ph2MeP)C6H4(BMes2)]+ 3+), tripling concentration (for NMR identifications) not only did
followed by [18F]-fluoride release in organic media triggered by the time to full conversion increase (see supp. Info), but a
tetrabutylammonium cyanide (TBACN). Furthermore, this white precipitate also appeared. We therefore hypothesized a
methodology has been validated towards subsequent plausible fluoride salt precipitation in the reaction media to
nucleophilic aromatic radiofluorination (Scheme 2).
explain the lack of observation of the fluoride release event by
NMR. As reported earlier,11 addition of 100 μL of D2O rendered
an homogeneous solution and further NMR studies revealed a
major peak δ(19F) -122.2 ppm, thus, indirectly corroborating
our hypothesis.
The
implementation
of
this
technology
towards
radiofluorination where [18F]-F- is produced at trace levels shall
provide propitious conditions to preclude such precipitation.
Hence we applied this fluoride trapping/release sequence to
radioactive conditions starting from aqueous [18F]-KF. The
[18F]-fluoride trapping/release process was then assessed
towards a model nucleophilic aromatic radiofluorination of
Scheme 2. Conversion of aqueous [ [
18F]-fluoride into organic 18F]-fluoride by the
trapping/release sequence from phosphonium borane 3+ via zwitterionic
[
18F]-
fluoroborate 3–F.
1,4-dinitrobenzene (4 5)
) to 4-[18F]-fluoronitrobenzene ([18F]-
(Scheme 3).19 A solution of complex [18F]-KF/K222 in a mixture
of water and CH3CN was added to borane 3+. After stirring at rt
for 5 min, the solution was evaporated to dryness at 110 °C
The phosphonium borane 3+ was synthesized following
literature precedents,10a and could be obtained in pure form
by medium pressure reverse phase chromatography at
multigram scale (36% over three steps). Treatment of 3+ with
CsF in acetone-H2O (10:1) afforded fluoroborate 3-F in 79%
isolated yield. Moreover, the reaction conditions could be
further optimized by reaction of 3+ with KF/K222 complex in
MeCN-H2O (1:1) at RT for 15 min. This conditions triggered
under a flow of nitrogen; a solution of
4 and TBACN in DMSO
was added to the residue. The mixture was heated to 150 °C
and analyzed by radioTLC and HPLC.
quantitative conversion of
evidenced by 11B and 19F NMR spectroscopy. Thus, the
3
+ to fluoroborate 3-F as it could be
characteristic δ(11B) peak of + at 77.9 ppm shifted to 4.8 ppm,
3
which matches the δ(11B) of 3-F. In addition, a new peak at -
175.9 ppm by 19F NMR was observed, which matches the
spectral identity of 3-F
.
Treatment of fluoroborate 3-F with KCN in MeCN-MeOH
under sonication for 5 min followed by 1 h conventional
stirring yielded the corresponding cyanide adduct 3-CN as a
white solid in 56% isolated yield [δ(11B) -13.3 ppm].13
Scheme 3. Radiosynthesis of 4-[18F]-fluoronitrobenzene [18F]-5 from aqueous [18F]-
fluoride via the capture/release approach or the “conventional” azeotropic drying
method.
However, in the absence of sonication and using MeCN alone
as a solvent, the total conversion of 3-F to cyanoborate 3-CN
required heating (90 °C, 15 min) given the poor solubility of 3-F
in MeCN. Conversion of the δ(11B) doublet at 4.8 ppm into a
Influence of the amount of TBACN was examined at 5 min
reaction time (Table 1). In the absence of TBACN, conversion
singlet peak at -13.3 ppm assessed the access to 3-CN
.
to [18F]-
5 did not exceed 12% (entry 1). The very poor
1
The structure of 3-CN has also been supported by H, 13C and
31P NMR. Suitable crystals for X-ray crystallography were
grown from vapour diffusion of TBME to a solution of 3-CN in
MeCN allowing an unambiguous confirmation of the structure
(see ESI).14 3-CN exhibits a B–C bond length of 1.625 Å similar
to the average value found in the Cambridge Structural
Database (CSD) for related cyanotriarylborate.15 The (BCN)
angle of 170.9° is among the smallest found for such
compounds within the CSD.16
conversions suggest that no [18F]-fluoride was available for
radiofluorination and that all radioactivity was in the form of
[18F]-3-F
Variable radiochemical yields in [18F]-
.
5
ranging from 2 to 32
(entry 2) were obtained using 0.1 equiv. of TBACN (with
respect to 3+). Radiochemical yields increased to 20-23% (entry
3) and 48-55% (entry 4) using 0.5 and 1 equiv. of TBACN
respectively, and expectedly lessened to 36-38% (entry 5) with
2 equiv. of TBACN. Based on these results, 1 equiv. of TBACN
The use of 1 equiv. of TBACN renders complete conversion of
the starting fluoroborate, albeit with formation of trace levels
- 17
was used to reach the optimal radiochemical yields in [18F]-
5.
As we demonstrated in our non-radioactive assays, 1 equiv. of
TBACN is sufficient to trigger [18F]-fluoride release from 3–F
(Scheme 2 and see supp. info). Moreover we also showed that
of BF4 . Apparition of the latter combined with the absence
of signals attributable to the release of fluoride did not appear
2 | J. Name., 2012, 00, 1-4
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 4
View Article Online
DOI: 10.1039/C6CC05168E
Journal Name
COMMUNICATION
nucleophilic attack of TBACN with unreacted 3+ provides a is mandatory as no radioactivity was trapped when this
concomitant process for the formation cyanoboronate 3-CN preliminary step was not performed (entry 1).
thus avoiding deleterious side-reactions and toxicity arising
from free cyanide.20
Table 1. Influence of TBACN amount in the radiofluorination of 4 to [18F]-5 in DMSO at
150 °C for 5 min via the [18F]-fluoride trapping/release method using 3+.
Entry
TBACN (equiv.)a
[ 5
18F]- (%)b
1
2
3
4
5
0
0.1
0.5
1
9-12
2-32
20-23
48-55
36-38
2
a against 1; b determined by radioTLC and HPLC of the crude mixture (n = 3).
Fig. 1 Schematic representation of the [18F]-fluoride cartridge-based trapping-release
approach using adsorbed phosphonium 3+ in the radiosynthesis of [18F]-5.
Influence of the reaction time was then studied using 1 equiv.
of TBACN (Table 2). Radiochemical yields were similar (47-52%,
entries 1-2) after 5 and 10 min, and decreased progressively
after 20 (24-30%, entry 3) and 30 min (14-18%, entry 4). For
Lowering the amount of 3+ below 20 mg resulted in a
significant decrease of the captured radioactivity (entries 2-4).
comparison and to validate the process, radiofluorination of
to [18F]-
4
5
was also performed in a back-to-back fashion using a
Table 3. [18F]-Fluoride trapping on cartridge pre-loaded with 3+.
conventional method (featuring azeotropic drying) with and
without 1 equiv. of TBACN (Table 2).
Load of 1
[
18F]-Fluoride trapping
(%)
Entry
(mg)
0
(ꢀmol)
0
Table 2. Comparison of the radiofluorination of 4 to [18F]-5 in DMSO at 150 °C via the
trapping-release sequence using 3+ or the conventional method with or without 1
equiv. TBACN
1
2
3
4
5
0 (n = 1)
5
7.7
40-45 (n = 5)
46-50 (n = 5)
44-50 (n = 5)
87-99 (n > 20)
10
15
20
15.4
23.1
30.8
[
18F]-5 (%)a
Conventional Azeotropic drying
Capture
Release
47-51
t
(min)
5
Using these optimised solid support trapping conditions, we
performed the capture of [18F]-fluoride on a pre-loaded
cartridge with 20 mg of borane 3
+, followed by flushing with a
Entry
Without TBACN
82-89
With TBACN
23-27
20-25
5-9
1
2
3
4
10
48-52
68-71
20
24-30
24-29
nitrogen gas flow to achieve total removal of water. Then, we
observed a quantitative elution of the radioactivity from the
cartridge using a dry solution of acetonitrile containing one
equivalent of TBACN (with respect to 3+). The final mixture was
30
14-18
12-17
0-3
a
Determined by radioTLC and HPLC of the crude product (n = 3, all assays
performed in parallel from the same [18F]fluoride production).
added to
4
in DMSO and the mixture heated at 150 °C.
increased with time reaching
Radiochemical yields in [18F]-
5
A similar decrease of the yield was observed probably as a
consequence of the degradation of [18F]-
5 under prolonged
48-55% at 20 min, and then slightly declined to 34-42% at 30
min (Table 4). Comparison of adsorbed and solution processes
highlights slower radiofluorination kinetics of the former. Yet
similar radiochemical yields and enhanced reproducibility were
achieved.
heating. In the presence of TBACN the conventional method
provided significantly lower radiochemical yields (as it can be
expected considering a competitive substitution of
4 and/or 5
by cyanide). Despite the evidenced deleterious effect of
TBACN in conventional methods, equimolar amounts of this
reagent are well tolerated in the presence of cationic boranes
thanks to the in situ formation of 3-CN by displacement of
Table 4. Yield of [18F]-5 using a cartridge based [18F]-fluoride trapping/release.
Entry
T (min)
[ 5
18F]- (%)a
fluoride from [18F]-3-F and conversion of excess 3+ to 3-CN
.
Finally, [18F]-fluoride trapping/release process was adapted to
solid-support through an adsorption strategy (Fig. 1). For that
purpose, a reversed-phase C18 cartridge21 was pre-loaded with
borane 3+ and elution of [18F]-KF/K222 in solution in
water/acetonitrile mixture was performed. The optimized
amount of 3+ was found to be 20 mg in order to capture the
major part (87-99%) of the radioactive fluoride on the support
(Table 3, entry 5). Preconditioning the cartridge with borane 3+
1
2
3
4
5
13-19
25-36
48-55
34-42
10
20
30
a determined by radioTLC and HPLC of the crude mixture (n = 5)
.
To showcase the efficiency of this process, we applied it to the
synthesis of [18F]-setoperone
7 (Fig. 2), a marker known for 5-
HT2 receptors used in clinical studies.22 The 25% radiochemical
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-4 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 4
View Article Online
DOI: 10.1039/C6CC05168E
COMMUNICATION
Journal Name
9.
a) V. Bernard-Gauthier, J. J. Bailey, Z. Liu, B. Wangler, C.
Wangler, K. Jurkschat, D. M. Perrin and R. Schirrmacher,
Bioconjugate Chem., 2016, 27, 267-279; b) Z. Liu, K. S. Lin,
F. Benard, M. Pourghiasian, D. O. Kiesewetter, D. M.
Perrin and X. Chen, Nat. Protoc., 2015, 10, 1423-1432; c)
D. M. Perrin, Acc. Chem. Res., 2016, DOI:
yield from
procedure.23
6 compares similarly with the conventional
10.1021/acs.accounts.5b00398;
d)
S.
Litau,
S.
Niedermoser, N. Vogler, M. Roscher, R. Schirrmacher, G.
Fricker, B. Wangler and C. Wangler, Bioconjugate Chem.,
2015, 26, 2350-2359; e) K. Chansaenpak, B. Vabre and F.
P. Gabbai, Chem. Soc. Rev., 2016, 45, 954-971; f) L. O.
Dialer, S. V. Selivanova, C. J. Muller, A. Muller, T. Stellfeld,
K. Graham, L. M. Dinkelborg, S. D. Kramer, R. Schibli, M.
Reiher and S. M. Ametamey, J. Med. Chem., 2013, 56,
7552-7563; g) K. L. Chatalic, G. M. Franssen, W. M. van
Weerden, W. J. McBride, P. Laverman, E. de Blois, B.
Hajjaj, L. Brunel, D. M. Goldenberg, J. A. Fehrentz, J.
Martinez, O. C. Boerman and M. de Jong, J. Nucl. Med.,
2014, 55, 2050-2056.
a) M. H. Lee, T. Agou, J. Kobayashi, T. Kawashima and F. P.
Gabbai, Chem. Commun., 2007, 1133-1135; b) T. W.
Hudnall and F. P. Gabbai, J. Am. Chem. Soc., 2007, 129,
11978-11986; c) T. W. Hudnall, Y. M. Kim, M. W.
Bebbington, D. Bourissou and F. P. Gabbai, J. Am. Chem.
Soc., 2008, 130, 10890-10891; d) Y. Kim and F. P. Gabbai,
J. Am. Chem. Soc., 2009, 131, 3363-3369.
Figure 2: [18F]-setoperone accessed by trapping-release approach.
In conclusion, we have established an efficient and
reproducible preparation of reactive [18F]-fluoride directly
from aqueous mixture without azeotropic distillation via a
capture/release strategy using phosphonium borane 3+. The
so-obtained [18F]-fluoride source was efficiently engaged in
aromatic nucleophilic substitutions demonstrating that this
approach successfully overcomes the need for azeotropic
distillation. Furthermore implementation of a cartridge-based
technology brings a user-friendly and time-saving method for
the production of [18F]-fluoride ready for use. A scope
development and further solid support–strategies are
currently underway.
10.
Financial support from ANR (ANR-12-BS07-0005-01), the
Cancer Prevention Research Institute of Texas (RP130604) and
the DPST project under Royal Thai Government (K.C.) for 11.
12.
H. Zhao and F. P. Gabbai, Org. Lett., 2011, 13, 1444-1446.
C. Bresner, C. J. E. Haynes, D. A. Addy, A. E. J.
Broomsgrove, P. Fitzpatrick, D. Vidovic, A. L. Thompson, I.
A. Fallis and S. Aldridge, New J. Chem., 2010, 34, 1652-
1659.
financial support and technical support from the LCC & ICT
scientific services are acknowledged.
13.
Alternatively, reaction of 3+ with TBACN in MeCN for 15
min at rt also led to quantitative conversion to 3-CN, as it
could be observed by 11B NMR.
Notes and references
1.
a) M.-C. Lasne, C. Perrio, J. Rouden, L. Barré, D. Roeda, F.
Dollé and C. Crouzel, Top. Curr. Chem., 2002, 222, 201-
258; b) S. Preshlock, M. Tredwell and V. Gouverneur,
Chem. Rev., 2016, 116, 719-766; c) M. G. Campbell and T.
Ritter, Chem. Rev., 2015, 115, 612-633.
14.
15.
16.
Crystallographic data have been deposited to the
Cambridge Crystallographic Data Centre as CCDC 1472439
This distance correspond to a 0.7% difference to the mean
distance value analyzed in CSD.
2.
3.
D. J. Schlyer, M. A. V. Bastos, D. Alexoff and A. P. Wolf,
App. Radiat. Isotopes, 1990, 41, 531-533.
The mean angle analyzed in the CSD for
triarylcyanoborate is 175.91° and the smallest angle
reported is 170.85°.
The nature of an azeotrope obviously prevents azeotropic
distillation to fully remove the water from the solution;
Thus azeotropic distillation removes most of the water,
but the amount of remaining water can not be assessed
during radiofluorination processes.
-
17.
18.
The characteristic peaks of BF4 appear at δ(11B) -1.2, and
δ(19F) -152.3 ppm.
a) H. Sun and S. G. DiMagno, Angew. Chem. Int. Ed., 2006,
45, 2720-2725; b) H. Sun and S. G. DiMagno, J. Am. Chem.
Soc., 2005, 127, 2050-2051.
4.
5.
6.
C. F. Lemaire, J. J. Aerts, S. Voccia, L. C. Libert, F. Mercier,
D. Goblet, A. R. Plenevaux and A. J. Luxen, Angew. Chem.
Int. Ed. Engl., 2010, 49, 3161-3164.
S. A. Toorongian, G. K. Mulholland, D. M. Jewett, M. A.
Bachelor and M. R. Kilbourn, Int. J. Rad. Appl. Instrum. B,
1990, 17, 273-279.
a) J. Aerts, S. Voccia, C. Lemaire, F. Giacomelli, D. Goblet,
D. Thonon, A. R. Plenevaux, G. Warnock and A. J. Luxen,
Tetrahedron Lett., 2010, 51, 64-66; b) D. M. Jewett, S. A.
Toorongian, G. K. Mulholland, G. L. Watkins and M. R.
Kilbourn, Int. J. Rad. Appl. Instrum. A, 1988, 39, 1109-
1111.
19.
20.
Aliphatic radiofluorinations proved so far less efficient.
Using 20 mg of 3-F requires 0.8 mg of cyanide prior to
complexation, far below the LD50 of free cyanide.
900 mg Sorbent per cartridge, 37-55 µm particle.
a) C.R. Di Iorio, T.J. Watkins, M.S. Dietrich, A. Cao, J.U.
Blackford, B. Rogers, M.S. Ansari, R.M. Baldwin, R. Li, R.M.
Kessler, R.M. Salomon, M. Benningfield and R.L. Cowan
Arch. Gen. Psychiatry 2012, 69, 399-409; b) L.N. Yatham,
P.F. Liddle, V. Sossi, J. Erez, N. Vafai, R.W. Lam and S.
Blinder Arch. Gen. Psychiatry 2012, 69, 601-609; c) D.Q.
Beversdorf, R.E. Nordgren, A.A. Bonab, A.J. Fischman, S.B.
Weise, D.D. Dougherty, G.J. Fetopulos, F.C. Zhou and M.L.
Bauman J. Neuropsychiatry Clin. Neurosci. 2012, 24, 191-
197
21.
22.
7.
8.
S. H. Wessmann, G. Henriksen and H.-J. Wester,
Nuklearmedizin, 2012, 51, 1-8.
S. Lindner, C. Rensch, S. Neubaur, M. Neumeier, R.
Salvamoser, V. Samper and P. Bartenstein, Chem.
Commun., 2016, 52, 729-732.
23.
C. Crouzel, M. Venet, T. Irie, G. Sanz, C. Boullais J. Label.
Compds Radiopharm. 1988, 25, 403-414.
4 | J. Name., 2012, 00, 1-4
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins