[en] Positron emission tomography combined with computed tomography (PET/CT) using RGD-based radiopharmaceuticals allows quantification of tumour expression of integrin αvβ3 in vivo. Integrins and, in particular, integrin αvβ3 are involved in numerous physiologic and pathologic processes, including angiogenesis. RGD-based radiopharmaceuticals targeting integrin αvβ3, expressed by activated endothelial cells, have been developed in order to quantify angiogenesis. However, integrin αvβ3 is also frequently expressed by tumour cells and/or tumour microenvironment cells, e.g., bone marrow derived cells and osteoclasts in bone. Upregulation of integrin αvβ3 by tumour cells promotes cell survival, proliferation, invasion, metastasis and resistance to treatment. Therefore, the PET signal related to RGD-based radiopharmaceuticals may not reflect angiogenesis only. Moreover, tumours may develop mechanisms other than angiogenesis to ensure blood supply such as vascular mimicry, vessel co-option and intussusceptive angiogenesis that might not be assessed with RGD PET/CT. In the setting of treatment assessment, a drop of the RGD PET signal certainly means tumour response (endothelial and/or tumour cell apoptosis and/or vessel normalisation). On the other hand, a stable or increased RGD PET signal may be related to absence of response or upregulation of integrin αvβ3 in adaptative response to therapy, promoting resistance. This review illustrates the complexity of the role of integrin αvβ3 in oncology and its role in non-oncologic diseases such as osteoarthtitis and cardiovascular diseases.
Disciplines :
Laboratory medicine & medical technology Oncology Radiology, nuclear medicine & imaging
Author, co-author :
WITHOFS, Nadia ; Centre Hospitalier Universitaire de Liège - CHU > Service médical de médecine nucléaire et imagerie onco
HUSTINX, Roland ; Centre Hospitalier Universitaire de Liège - CHU > Service médical de médecine nucléaire et imagerie onco
Language :
English
Title :
Integrin αvβ3 and RGD-based radiopharmaceuticals
Alternative titles :
[en] L’intégrine αvβ3 et l’imagerie par les radiopharmaceutiques de type RGD
Publication date :
19 February 2016
Journal title :
Médecine Nucléaire: Imagerie Fonctionnelle et Métabolique
ISSN :
0928-1258
eISSN :
1878-6820
Publisher :
Elsevier, Paris, France
Volume :
40 (2016)
Pages :
41-54
Peer reviewed :
Peer reviewed
Commentary :
Résumé: Les radiopharmaceutiques de type RGD dédiés à l’imagerie par tomographie à émission de positons associée à la tomodensitométrie (TEP/ TDM) permettent la quantification de l’expression de l’intégrine αvβ3 in vivo. Les intégrines et, en particulier, l’intégrine αvβ3 sont impliquées dans de nombreux processus physiologiques et pathologiques, parmi lesquels l’angiogenèse. Les radiopharmaceutiques de type RGD ciblant l’intégrine αvβ3, exprimée par les cellules endothéliales activées, ont été développés afin de quantifier l’angiogenèse. Cependant, l’intégrine αvβ3 est également souvent exprimée par les cellules tumorales et/ou des cellules du microenvironnement de la tumeur comme, par exemple, des cellules dérivées de la moelle osseuse et les ostéoclastes dans l’os. De plus, l’intégrine αvβ3 peut être surexprimée par les cellules tumorales, favorisant la survie cellulaire, la prolifération, l’invasion, le potentiel métastatique et la résistance au traitement. Par conséquent, le signal PET lié au RGD peut ne pas refléter l’angiogenèse uniquement. En outre, les tumeurs peuvent développer des mécanismes autres que l’angiogenèse tels que le mimétisme vasculaire, la cooptation vasculaire et l’angiogenèse intussusceptive qui pourraient ne pas être visualisés par TEP/TDM au RGD. Dans le cadre de l’évaluation des traitements antiangiogéniques, une baisse de la captation du traceur RGD en TEP signifie certainement une réponse tumorale liée à l’apoptose des cellules endothéliales et/ou tumorales et/ou à la normalisation des vaisseaux. D’autre part, la stabilité, voire l’augmentation, de la captation du traceur RGD en cours de traitement pourrait être le reflet de l’absence de réponse mais également de la surexpression de l’intégrine αvβ3 en réponse adaptative au traitement favorisant la résistance tumorale. Cette revue illustre la complexité du rôle de l’intégrine αvβ3 en oncologie et décrit son rôle dans les maladies non-oncologiques telles que les maladies cardiovasculaires et l’arthrose.
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