Noninvasive Imaging of CCR2+Cells in Ischemia-Reperfusion Injury After Lung Transplantation.
Ischemia-reperfusion injury-mediated primary graft dysfunction substantially hampers short- and long-term outcomes after lung transplantation. This condition continues to be diagnosed based on oxygen exchange parameters as well as radiological appearance, and therapeutic strategies are mostly supportive in nature. Identifying patients who may benefit from targeted therapy would therefore be highly desirable. Here, we show that C-C chemokine receptor type 2 (CCR2) expression in murine lung transplant recipients promotes monocyte infiltration into pulmonary grafts and mediates graft dysfunction. We have developed new positron emission tomography imaging agents using a CCR2 binding peptide, ECLi1, that can be used to monitor inflammatory responses after organ transplantation. Both64Cu-radiolabeled ECL1i peptide radiotracer (64Cu-DOTA-ECL1i) and ECL1i-conjugated gold nanoclusters doped with64Cu (64CuAuNCs-ECL1i) showed specific detection of CCR2, which is upregulated during ischemia-reperfusion injury after lung transplantation. Due to its fast pharmacokinetics,64Cu-DOTA-ECL1i functioned efficiently for rapid and serial imaging of CCR2. The multivalent64CuAuNCs-ECL1i with extended pharmacokinetics is favored for long-term CCR2 detection and potential targeted theranostics. This imaging may be applicable for diagnostic and therapeutic purposes for many immune-mediated diseases.
Department of Radiology, Washington University School of Medicine, St. Louis, MO.
Y
Y
Liu
Department of Surgery, Washington University School of Medicine, St. Louis, MO.
W
W
Li
Department of Radiology, Washington University School of Medicine, St. Louis, MO.
H P
HP
Luehmann
Department of Radiology, Washington University School of Medicine, St. Louis, MO.
Y
Y
Zhao
Department of Radiology, Washington University School of Medicine, St. Louis, MO.
L
L
Detering
Department of Radiology, Washington University School of Medicine, St. Louis, MO.
D H
DH
Sultan
Department of Surgery, Washington University School of Medicine, St. Louis, MO.
H-M
HM
Hsiao
Department of Surgery, Washington University School of Medicine, St. Louis, MO.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
A S
AS
Krupnick
Department of Surgery, Washington University School of Medicine, St. Louis, MO.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
A E
AE
Gelman
Sorbonne Universités, UPMC Univ Paris 06, INSERM, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
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C
Combadiere
Department of Radiology, Washington University School of Medicine, St. Louis, MO.
R J
RJ
Gropler
Department of Radiology, Washington University School of Medicine, St. Louis, MO.|Department of Medicine, Washington University School of Medicine, St. Louis, MO.
S L
SL
Brody
Department of Surgery, Washington University School of Medicine, St. Louis, MO.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
D
D
Kreisel
D000818:Animals; D016040:Lung Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D054390:Receptors, CCR2 / Q000502:physiology*; D015427:Reperfusion Injury / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
C515335:Ccr2 protein, mouse; D010446:Peptide Fragments; D054390:Receptors, CCR2
basic (laboratory) research/science; diagnostic techniques and imaging: positron emission tomography; ischemia reperfusion injury (IRI); lung transplantation/pulmonology