Cardiovascular Images
[68Ga]Pentixafor–Positron Emission Tomography/Computed
Tomography Detects Chemokine Receptor CXCR4
Expression After Ischemic Stroke
Jan Stefan Schmid, MD; Andreas Schirbel, PhD; Andreas K. Buck, MD; Saskia Kropf, MSc;
Hans-Jürgen Wester, PhD; Constantin Lapa, MD

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64-year-old female with primarily diagnosed small cell
lung cancer was referred to our department for positron
emission tomography (PET)/computed tomography work-up
with [18F]FDG and [68Ga]Pentixafor, a radiotracer for CXCmotif chemokine receptor 4, with the latter being performed
on a compassionate use basis in compliance with Section 37 of
the Declaration of Helsinki, the German Medicinal Products
Act, AMG Section 13 2b, and in accordance with the responsible regulatory body (Regierung von Oberfranken) to check
for a potential therapeutic option in this patient. Diagnosis had
been established 4 weeks earlier when the patient presented to
the emergency room with new-onset aphasia (word retrieval).
Cerebral magnetic resonance imaging revealed a contrastenhancing mass in the left temporal region, which was histopathologically confirmed as small cell lung cancer metastasis.
The day after brain surgery, the patient experienced acute
ischemic stroke in the right posterior cerebral artery territory.
At the day of presentation to our nuclear medicine department, she reported on recovering hemianopia, and no other
neurological symptoms could be recorded.
Concerning the suspected lung carcinoma, both PET
modalities visualized a solitary lesion in the upper lobe of
the right lung, highly consistent with the suspected primary
(Figure 1). In the central nervous system, however, imaging
with [18F]FDG-PET demonstrated markedly reduced glucose metabolism in the infarction area, whereas CXC-motif
chemokine receptor 4–directed PET visualized concordantly
increased receptor expression (Figure 2).
Recently, proof-of-concept for visualization of CXC-motif
chemokine receptor 4 expression by [68Ga]Pentixafor, a radiolabeled, highly human-specific receptor ligand for PET imaging,
has been demonstrated in patients with small cell lung cancer and

other (hematologic) diseases.1 Although the feasibility of [68Ga]
Pentixafor PET imaging has not been studied in experimental
models of ischemic stroke yet, the stromal cell–derived factor 1α/
CXC-motif chemokine receptor 4 axis has been shown to play
an important role in the recruitment of inflammatory and stem
and progenitor cells to the areas of ischemic injury after both
myocardial infarction2 and ischemic stroke.3,4 Its noninvasive, in
vivo visualization might lead to novel insights into the course and
prognostic implications of postischemic inflammatory response.

Disclosures
Dr Wester is the founder and shareholder of Scintomics. S. Kropf is
CEO of Scintomics. The other authors report no conflicts.

References
1. Lapa C, Lückerath K, Rudelius M, Schmid JS, Schoene A, Schirbel A,
Samnick S, Pelzer T, Buck AK, Kropf S, Wester HJ, Herrmann K. [68Ga]
Pentixafor-PET/CT for imaging of chemokine receptor 4 expression in
small cell lung cancer–initial experience. Oncotarget. 2016;7:9288–
9295. doi: 10.18632/oncotarget.7063.
2. Lapa C, Reiter T, Werner RA, Ertl G, Wester HJ, Buck AK, Bauer WR,
Herrmann K. [(68)Ga]Pentixafor-PET/CT for imaging of chemokine
receptor 4 expression after myocardial infarction. JACC Cardiovasc
Imaging. 2015;8:1466–1468. doi: 10.1016/j.jcmg.2015.09.007.
3. Hill WD, Hess DC, Martin-Studdard A, Carothers JJ, Zheng J, Hale
D, Maeda M, Fagan SC, Carroll JE, Conway SJ. SDF-1 (CXCL12) is
upregulated in the ischemic penumbra following stroke: association
with bone marrow cell homing to injury. J Neuropathol Exp Neurol.
2004;63:84–96.
4. Schönemeier B, Schulz S, Hoellt V, Stumm R. Enhanced expression
of the CXCl12/SDF-1 chemokine receptor CXCR7 after cerebral ischemia in the rat brain. J Neuroimmunol. 2008;198:39–45. doi: 10.1016/j.
jneuroim.2008.04.010.
Key Words: aphasia ◼ CXCR4 ◼ positron emission tomography ◼ small
cell lung carcinoma ◼ stroke

From the Department of Nuclear Medicine, University Hospital Würzburg, Germany (J.S.S., A.S., A.K.B., C.L.); Scintomics GmbH, Fürstenfeldbruck,
Germany (S.K.); and Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany (H.-J.W.).
Correspondence to Constantin Lapa, MD, Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacher Str 6, 97080 Würzburg,
Germany. E-mail Lapa_c@ukw.de
(Circ Cardiovasc Imaging. 2016;9:e005217. DOI: 10.1161/CIRCIMAGING.116.005217.)
© 2016 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org

1

DOI: 10.1161/CIRCIMAGING.116.005217

2  Schmid et al  CXCR4 After Stroke

Figure 1. Display of representative axial slices of computed tomography ([CT], A) and [18F]FDG- (B) and CXCR4 (C)-directed positron
emission tomography (PET). All modalities present a pulmonary lesion in the right upper lobe, highly consistent with lung cancer. CXCR
indicates CXC-motif chemokine receptor.

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Figure 2. Cerebral magnetic resonance imaging (cMRI) at day 2 after brain surgery shows demarcation of right posterior ischemia with
corresponding changes in diffusion-weighted images (A; b value =1000 s/mm2) and apparent diffusion coefficient values (B). [18F]FDGPET demonstrates significantly reduced tracer uptake in the infarction area (C). In contrast, [68Ga]Pentixafor-PET (one day later) visualizes upregulation of CXCR4 (D, Inset; maximum intensity projection; standardized uptake valuemax =4.08 versus standardized uptake
valuemediastinal bloodpool =1.62), which correlates with cMRI changes (E, DWI/PET fusion). CXCR indicates CXC-motif chemokine receptor;
DWI, diffusion-weighted image; and PET, positron emission tomography.