FULL PAPER
DOI: 10.1002/chem.201203455
19
Parahydrogen-Induced Polarization Transfer to F in Perfluorocarbons
19
for F NMR Spectroscopy and MRI**
Markus Plaumann,*[a] Ute Bommerich,[b] Thomas Trantzschel,[a] Denise Lego,[b]
Sonja Dillenberger,[c] Grit Sauer,[c] Joachim Bargon,[d] Gerd Buntkowsky,[c] and
Johannes Bernarding[a]
Abstract: Fluorinated substances are
important in chemistry, industry, and
the life sciences. In a new approach,
zation despite the negligible coupling
to the added protons. To clarify this
non-intuitive distribution of polariza-
tion, signal enhancements in deuterat-
ed chloroform and acetone were com-
pared and 19F–19F NOESY spectra, as
well as 19F T1 values were measured by
NMR spectroscopy. By using the well
separated and enhanced signal of the
CF3 group, first 19F MR images of hy-
perpolarized linear semifluorinated al-
kenes were recorded.
parahydrogen-induced
polarization
(PHIP) is applied to enhance 19F MR
signals of (perfluoro-n-hexyl)ethene
and (perfluoro-n-hexyl)ethane. Unex-
pectedly, the end-standing CF3 group
exhibits the highest amount of polari-
Keywords: fluorine
·
hydrogena-
tion · imaging agents · NMR spec-
troscopy · polarization transfer
Introduction
shift range of more than 300 ppm and no natural fluorine
background signal in biological organisms. Therefore, signals
can be attributed unambiguously. Similarly, 19F MRI has re-
cently become an important research topic in medicine with
a focus on molecular imaging applications, lung imaging,
and drug monitoring.[5] Although this shows that 19F MRI
has a high potential to serve as a new diagnostic tool, the in
vivo spin density of most substrates is rather small, leading
to low signal-to-noise ratios (SNRs). Hence, strong efforts
aim to increase the 19F SNR as the prerequisite to establish
MR in clinical and medical routine.
Instead of increasing the external polarizing magnetic
field, less costly but very efficient non-standard polarization
methods offer a new way to acquire signals with higher
SNR. Hyperpolarization techniques such as dynamic nuclear
polarization (DNP), chemically induced dynamic nuclear
polarization (CIDNP), spin-exchange optical pumping
(SEOP), and parahydrogen-induced polarization (PHIP)
can be used to enhance the SNR in MR experiments up to
several orders of magnitude. In general, these methods gen-
erate populations of the Zeeman energy levels that differ
significantly from the limited thermal polarization.[6,7] PHIP
is advantageous because its implementation requires less
technological effort. PHIP signals depend on whether hy-
drogenation is performed in the presence of a strong mag-
netic field (PASADENA, parahydrogen and synthesis allow
dramatically enhanced nuclear alignment),[8] or whether hy-
drogenation occurs under low-field conditions (ALTADE-
NA, adiabatic longitudinal transfer after dissociation engen-
ders net alignment) followed by adiabatic transport into the
detection field.[9]
In the last few years, perfluorinated molecules have been
raising increasing interest. They are of great relevance in
technical, chemical, and life science applications due to their
manifold, excellent characteristics.[1] One of the most stud-
ied perfluorinated compounds in medicine is the linear per-
fluorooctylbromide (C8F15Br), also known as perflubron,
which can be used as a blood substitute as well as a contrast
agent in 19F magnetic resonance imaging (MRI).[2] In gener-
al, perfluorocarbons are well known from in vivo studies in
different applications, for example, artificial blood, liquid
breathing,[3] and in 19F MRI studies.[4]
19F NMR spectroscopy has a long-standing history in high-
resolution NMR spectroscopy as there is a high chemical-
[a] Dr. M. Plaumann, Dipl.-Phys. T. Trantzschel, Prof. Dr. J. Bernarding
Department of Biometry and Medical Informatics
Otto-von-Guericke University of Magdeburg
Leipziger Strasse 44, 39120 Magdeburg (Germany)
Fax : (+49)391-67-13536
[b] Dr. U. Bommerich, Dipl.-Ing. D. Lego
Leibniz-Institute for Neurobiology
39118 Magdeburg (Germany)
[c] Dipl.-Chem. S. Dillenberger, Dipl.-Chem. G. Sauer,
Prof. Dr. G. Buntkowsky
Eduard-Zintl-Institute for Inorganic Chemistry
Technical University Darmstadt
64287 Darmstadt (Germany)
[d] Prof. Dr. J. Bargon
Institute of Physical and Theoretical Chemistry
University Bonn, 53115 Bonn (Germany)
PHIP can be used, for example, for analyzing intermedi-
ates and products of catalytic reactions or, as recently re-
ported, also for biological and medical studies by polariza-
[**] MRI=magnetic resonance imaging.
Supporting information for this article is available on the WWW
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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