[68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure
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[68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure. / Bentsen, Simon; Jensen, Jacob Kildevang; Christensen, Esben; Petersen, Lars Ringgaard; Grandjean, Constance Eline; Follin, Bjarke; Madsen, Johanne Straarup; Christensen, Camilla; Clemmensen, Andreas; Binderup, Tina; Hasbak, Philip; Ripa, Rasmus Sejersten; Kjaer, Andreas.
In: Journal of Nuclear Cardiology, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - [68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure
AU - Bentsen, Simon
AU - Jensen, Jacob Kildevang
AU - Christensen, Esben
AU - Petersen, Lars Ringgaard
AU - Grandjean, Constance Eline
AU - Follin, Bjarke
AU - Madsen, Johanne Straarup
AU - Christensen, Camilla
AU - Clemmensen, Andreas
AU - Binderup, Tina
AU - Hasbak, Philip
AU - Ripa, Rasmus Sejersten
AU - Kjaer, Andreas
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Background: Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin αvβ3 is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [68Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters. Methods: First, the real-time interaction between [68Ga]Ga-RGD and integrin αvβ3 was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [68Ga]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [68Ga]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry. Results: SPR showed that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, forming a strong and stable binding. PET/CT showed a significantly higher uptake of [68Ga]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [68Ga]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = − 0.71, p < 0.001) after four weeks. Conclusion: This study demonstrates that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, which enables the evaluation of angiogenesis and remodeling. The [68Ga]Ga-RGD uptake after one week indicates that [68Ga]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients.
AB - Background: Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin αvβ3 is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [68Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters. Methods: First, the real-time interaction between [68Ga]Ga-RGD and integrin αvβ3 was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [68Ga]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [68Ga]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry. Results: SPR showed that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, forming a strong and stable binding. PET/CT showed a significantly higher uptake of [68Ga]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [68Ga]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = − 0.71, p < 0.001) after four weeks. Conclusion: This study demonstrates that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, which enables the evaluation of angiogenesis and remodeling. The [68Ga]Ga-RGD uptake after one week indicates that [68Ga]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients.
KW - coronary artery disease
KW - Myocardial biology
KW - myocardial ischemia and infarction
KW - positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=85154557569&partnerID=8YFLogxK
U2 - 10.1007/s12350-023-03265-9
DO - 10.1007/s12350-023-03265-9
M3 - Journal article
C2 - 37127725
AN - SCOPUS:85154557569
JO - Journal of Nuclear Cardiology
JF - Journal of Nuclear Cardiology
SN - 1071-3581
ER -
ID: 347793355