PET imaging of a collagen matrix reveals its effective injection and targeted retention in a mouse model of myocardial infarction.
Injectable biomaterials have shown promise for cardiac regeneration therapy. However, little is known regarding their retention and distribution upon application in vivo. Matrix imaging would be useful for evaluating these important properties. Herein, hexadecyl-4-[(18)F]fluorobenzoate ((18)F-HFB) and Qdot labeling was used to evaluate collagen matrix delivery in a mouse model of myocardial infarction (MI). At 1 wk post-MI, mice received myocardial injections of (18)F-HFB- or Qdot-labeled matrix to assess its early retention and distribution (at 10 min and 2h) by positron emission tomography (PET), or fluorescence imaging, respectively. PET imaging showed that the bolus of matrix at 10 min redistributed evenly within the ischemic territory by 2h. Ex vivo biodistribution revealed myocardial matrix retention of ∼ 65%, which correlated with PET results, but may be an underestimate since (18)F-HFB matrix labeling efficiency was ∼ 82%. For covalently linked Qdots, labeling efficiency was ∼ 96%. Ex vivo Qdot quantification showed that ∼ 84% of the injected matrix was retained in the myocardium. Serial non-invasive PET imaging and validation by fluorescence imaging confirmed the effectiveness of the collagen matrix to be retained and redistributed within the infarcted myocardium. This study identifies matrix-targeted imaging as a promising modality for assessing the biodistribution of injectable biomaterials for application in the heart.
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
Ali
A
Ahmadi
Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
Stephanie L
SL
Thorn
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
Emilio I
EI
Alarcon
Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
Myra
M
Kordos
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
Donna T
DT
Padavan
Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
Tayebeh
T
Hadizad
Department of Medical Imaging, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada.
Greg O
GO
Cron
Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Division of Cardiology, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
Rob S
RS
Beanlands
Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal Hospital Research Centre, Montréal H2X 0A9, Canada.
Jean N
JN
DaSilva
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
Marc
M
Ruel
Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada. Electronic address: radekemp@ottawaheart.ca.
Robert A
RA
deKemp
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada. Electronic address: esuuronen@ottawaheart.ca.
Erik J
EJ
Suuronen
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000000981:diagnostic imaging*; D005260:Female; D005453:Fluorescence; D019788:Fluorodeoxyglucose F18; D007267:Injections; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D045663:Quantum Dots; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
D019788:Fluorodeoxyglucose F18; D003094:Collagen
Biomaterials; Collagen matrix; Fluorescence imaging; Injectable; PET imaging