Reza Golestani1,2, Leila Mirfeizi3, Clark J Zeebregts4, Johanna Westra5, Hans J de Haas3, Andor W J M Glaudemans3, Michel Koole3, Gert Luurtsema3, René A Tio6, Rudi A J O Dierckx3,7, Hendrikus H Boersma3,8, Philip H Elsinga3, Riemer H J A Slart3,9. 1. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands. reza.golestani@yale.edu. 2. Cardiovascular Medicine Section, Department of Internal Medicine, Yale University, New Haven, CT, USA. reza.golestani@yale.edu. 3. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands. 4. Division of Vascular Surgery, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 5. Department of Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 6. Department of Cardiology, Thorax Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 7. Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium. 8. Department of Clinical and Hospital Pharmacy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 9. Faculty of Science and Technology, Biomedical Photonic Imaging, University of Twente, Enschede, The Netherlands.
Abstract
BACKGROUND: Inflammation and angiogenesis play an important role in atherosclerotic plaque rupture. Therefore, molecular imaging of these processes could be used for determination of rupture-prone atherosclerotic plaques. αvβ3 integrin is involved in the process of angiogenesis. Targeted imaging of αvβ3 integrin has been shown to be possible in previous studies on tumor models, using radiolabeled arginine-glycine-aspartate (RGD). Our aim was to investigate feasibility of ex vivo detection of αvβ3 integrin in carotid endarterectomy (CEA) specimens. METHODS AND RESULTS: Nineteen CEA specimens were incubated in 5 MBq [18F]-RGD-K5 for 1 hour followed by 1 hour emission microPET scan. The results were quantified in 4 mm wide segments as percent incubation dose per gram (%Inc/g). Segmental-to-total ratio was calculated and presence of αvβ3 integrin and endothelial cells in each segment was confirmed by immunohistochemical staining for CD31 and αvβ3 integrin, respectively. [18F]-RGD-K5 uptake was heterogeneously distributed across CEA specimens and was localized within the vessel wall. Significant correlations were observed between segmental-to-total ratio with αvβ3 integrin staining score (r = 0.58, P = .038) and CD31 staining score (ρ = 0.67, P < .002). CONCLUSION: This study showed the feasibility of integrin imaging by determination of αvβ3 integrin expression in human atherosclerotic plaques.
BACKGROUND: Inflammation and angiogenesis play an important role in atherosclerotic plaque rupture. Therefore, molecular imaging of these processes could be used for determination of rupture-prone atherosclerotic plaques. αvβ3 integrin is involved in the process of angiogenesis. Targeted imaging of αvβ3 integrin has been shown to be possible in previous studies on tumor models, using radiolabeled arginine-glycine-aspartate (RGD). Our aim was to investigate feasibility of ex vivo detection of αvβ3 integrin in carotid endarterectomy (CEA) specimens. METHODS AND RESULTS: Nineteen CEA specimens were incubated in 5 MBq [18F]-RGD-K5 for 1 hour followed by 1 hour emission microPET scan. The results were quantified in 4 mm wide segments as percent incubation dose per gram (%Inc/g). Segmental-to-total ratio was calculated and presence of αvβ3 integrin and endothelial cells in each segment was confirmed by immunohistochemical staining for CD31 and αvβ3 integrin, respectively. [18F]-RGD-K5 uptake was heterogeneously distributed across CEA specimens and was localized within the vessel wall. Significant correlations were observed between segmental-to-total ratio with αvβ3 integrin staining score (r = 0.58, P = .038) and CD31 staining score (ρ = 0.67, P < .002). CONCLUSION: This study showed the feasibility of integrin imaging by determination of αvβ3 integrin expression in humanatherosclerotic plaques.
Authors: Xiaoxia Z West; Nikolay L Malinin; Alona A Merkulova; Mira Tischenko; Bethany A Kerr; Ernest C Borden; Eugene A Podrez; Robert G Salomon; Tatiana V Byzova Journal: Nature Date: 2010-10-03 Impact factor: 49.962
Authors: Ming Kai Lam; Sali Al-Ansari; Gooitzen M van Dam; René A Tio; Jan-Cees Breek; Riemer H J A Slart; Jan-Luuk Hillebrands; Clark J Zeebregts Journal: Mol Imaging Biol Date: 2013-06 Impact factor: 3.488
Authors: Morteza Naghavi; Peter Libby; Erling Falk; S Ward Casscells; Silvio Litovsky; John Rumberger; Juan Jose Badimon; Christodoulos Stefanadis; Pedro Moreno; Gerard Pasterkamp; Zahi Fayad; Peter H Stone; Sergio Waxman; Paolo Raggi; Mohammad Madjid; Alireza Zarrabi; Allen Burke; Chun Yuan; Peter J Fitzgerald; David S Siscovick; Chris L de Korte; Masanori Aikawa; K E Juhani Airaksinen; Gerd Assmann; Christoph R Becker; James H Chesebro; Andrew Farb; Zorina S Galis; Chris Jackson; Ik-Kyung Jang; Wolfgang Koenig; Robert A Lodder; Keith March; Jasenka Demirovic; Mohamad Navab; Silvia G Priori; Mark D Rekhter; Raymond Bahr; Scott M Grundy; Roxana Mehran; Antonio Colombo; Eric Boerwinkle; Christie Ballantyne; William Insull; Robert S Schwartz; Robert Vogel; Patrick W Serruys; Goran K Hansson; David P Faxon; Sanjay Kaul; Helmut Drexler; Philip Greenland; James E Muller; Renu Virmani; Paul M Ridker; Douglas P Zipes; Prediman K Shah; James T Willerson Journal: Circulation Date: 2003-10-07 Impact factor: 29.690
Authors: Iina Laitinen; Antti Saraste; Eliane Weidl; Thorsten Poethko; Axel W Weber; Stephan G Nekolla; Pia Leppänen; Seppo Ylä-Herttuala; Gabriele Hölzlwimmer; Axel Walch; Irene Esposito; Hans-Jürgen Wester; Juhani Knuuti; Markus Schwaiger Journal: Circ Cardiovasc Imaging Date: 2009-05-13 Impact factor: 7.792
Authors: Wouter B Nagengast; Elisabeth G de Vries; Geke A Hospers; Nanno H Mulder; Johan R de Jong; Harry Hollema; Adrienne H Brouwers; Guus A van Dongen; Lars R Perk; Marjolijn N Lub-de Hooge Journal: J Nucl Med Date: 2007-07-13 Impact factor: 10.057
Authors: Roland Haubner; Wolfgang A Weber; Ambros J Beer; Eugenija Vabuliene; Daniel Reim; Mario Sarbia; Karl-Friedrich Becker; Michael Goebel; Rüdiger Hein; Hans-Jürgen Wester; Horst Kessler; Markus Schwaiger Journal: PLoS Med Date: 2005-03-29 Impact factor: 11.069
Authors: Kornelis S M van der Geest; Maria Sandovici; Pieter H Nienhuis; Riemer H J A Slart; Peter Heeringa; Elisabeth Brouwer; William F Jiemy Journal: Front Med (Lausanne) Date: 2022-06-06