Angiogenesis PET tracer uptake (68Ga-NODAGA-E[(cRGDyK)]2) in induced myocardial infarction and stromal cell treatment inminipigs

Thomas Rasmussen; Bjarke Follin; Jens Kastrup; Malene Brandt-Larsen; Jacob Madsen; Thomas Emil Christensen; Morten Juhl; Smadar Cohen; Karsten Pharao Hammelev; Christian Holdflod Møller; Jens Peter Goetze; Philip Hasbak; Andreas Kjær

doi:10.3390/diagnostics8020033

Angiogenesis PET tracer uptake (⁶⁸Ga-NODAGA-E[(cRGDyK)]₂) in induced myocardial infarction and stromal cell treatment inminipigs

Thomas Rasmussen, Bjarke Follin, Jens Kastrup, Malene Brandt-Larsen, Jacob Madsen, Thomas Emil Christensen, Morten Juhl, Smadar Cohen, Karsten Pharao Hammelev, Christian Holdflod Møller, Jens Peter Goetze, Philip Hasbak, Andreas Kjær

Department of Biotechnology Engineering

Ben-Gurion University of the Negev

Research output: Contribution to journal › Article › peer-review

Abstract

Angiogenesis is considered integral to the reparative process after ischemic injury. The α_vβ₃ integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. ⁶⁸Ga-NODAGA-E[(cRGDyK)]₂ (RGD) is a positron-emission-tomography (PET) ligand targeted towards α_vβ₃ integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by ⁸²Rubidium (⁸²Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUV_mean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUV_mean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUV_mean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated.

Original language	American English
Article number	33
Journal	Diagnostics
Volume	8
Issue number	2
DOIs	https://doi.org/10.3390/diagnostics8020033
State	Published - 1 Jun 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Angiogenesis
Cardiac positron-emission-tomography
Hydrogel
Mesenchymal stromal cells
Myocardial perfusion
RGD
Rubidium
Stemcell;myocardial infarction

All Science Journal Classification (ASJC) codes

Clinical Biochemistry

Access to Document

10.3390/diagnostics8020033

Cite this

Rasmussen, T., Follin, B., Kastrup, J., Brandt-Larsen, M., Madsen, J., Christensen, T. E., Juhl, M., Cohen, S., Hammelev, K. P., Møller, C. H., Goetze, J. P., Hasbak, P., & Kjær, A. (2018). Angiogenesis PET tracer uptake (⁶⁸Ga-NODAGA-E[(cRGDyK)]₂) in induced myocardial infarction and stromal cell treatment inminipigs. Diagnostics, 8(2), Article 33. https://doi.org/10.3390/diagnostics8020033

@article{7759a6d646874953b6a0ef61b97d2c2f,

title = "Angiogenesis PET tracer uptake (68Ga-NODAGA-E[(cRGDyK)]2) in induced myocardial infarction and stromal cell treatment inminipigs",

abstract = "Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated.",

keywords = "Angiogenesis, Cardiac positron-emission-tomography, Hydrogel, Mesenchymal stromal cells, Myocardial perfusion, RGD, Rubidium, Stemcell;myocardial infarction",

author = "Thomas Rasmussen and Bjarke Follin and Jens Kastrup and Malene Brandt-Larsen and Jacob Madsen and Christensen, \{Thomas Emil\} and Morten Juhl and Smadar Cohen and Hammelev, \{Karsten Pharao\} and M{\o}ller, \{Christian Holdflod\} and Goetze, \{Jens Peter\} and Philip Hasbak and Andreas Kj{\ae}r",

note = "Publisher Copyright: {\textcopyright} 2018 by the authors.",

year = "2018",

month = jun,

day = "1",

doi = "10.3390/diagnostics8020033",

language = "American English",

volume = "8",

journal = "Diagnostics",

issn = "2075-4418",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "2",

}

Rasmussen, T, Follin, B, Kastrup, J, Brandt-Larsen, M, Madsen, J, Christensen, TE, Juhl, M, Cohen, S, Hammelev, KP, Møller, CH, Goetze, JP, Hasbak, P & Kjær, A 2018, 'Angiogenesis PET tracer uptake (⁶⁸Ga-NODAGA-E[(cRGDyK)]₂) in induced myocardial infarction and stromal cell treatment inminipigs', Diagnostics, vol. 8, no. 2, 33. https://doi.org/10.3390/diagnostics8020033

TY - JOUR

T1 - Angiogenesis PET tracer uptake (68Ga-NODAGA-E[(cRGDyK)]2) in induced myocardial infarction and stromal cell treatment inminipigs

AU - Rasmussen, Thomas

AU - Follin, Bjarke

AU - Kastrup, Jens

AU - Brandt-Larsen, Malene

AU - Madsen, Jacob

AU - Christensen, Thomas Emil

AU - Juhl, Morten

AU - Cohen, Smadar

AU - Hammelev, Karsten Pharao

AU - Møller, Christian Holdflod

AU - Goetze, Jens Peter

AU - Hasbak, Philip

AU - Kjær, Andreas

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated.

AB - Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated.

KW - Angiogenesis

KW - Cardiac positron-emission-tomography

KW - Hydrogel

KW - Mesenchymal stromal cells

KW - Myocardial perfusion

KW - RGD

KW - Rubidium

KW - Stemcell;myocardial infarction

UR - http://www.scopus.com/inward/record.url?scp=85082510273&partnerID=8YFLogxK

U2 - 10.3390/diagnostics8020033

DO - 10.3390/diagnostics8020033

M3 - Article

SN - 2075-4418

VL - 8

JO - Diagnostics

JF - Diagnostics

IS - 2

M1 - 33

ER -