Angiogenesis in PET studies

The process of new blood vessel growth by sprouting from existing vessels in microvasculature (angiogenesis) is essential for tissue growth and regeneration, and it is strictly controlled by angiogenic stimulators and inhibitors. Vascular remodelling is the process where the arrangement and structure of existing vessels is changed through cell growth, apoptosis, migration, and production or degradation of the extracellular matrix (ECM).

Angiogenesis is often triggered by tissue hypoxia. Hypoxia-inducible factor HIFα activates expression of vascular endothelial growth factor (VEGF). Inflammation, and metabolic and mechanical stress can also induce angiogenic process. Integrins are needed in endothelial cell growth, differentiation, adhesion, and migration.

Angiogenic processes can be detected with numerous PET radioligands, including labelled integrin αvβ3 antagonists, ECM matrix metalloproteinase (MPP) inhibitors, and natriuretic peptides. Tracers for VEGF-receptor and endoglin (CD105) have also been developed (Hong et al., 2014; Hendrikx et al., 2016). For instance, PET tracers targeting endoglin have been used in treatment follow-up in peripheral artery disease animal models.

Arteriogenesis

Arteriogenesis is not induced by hypoxia and ischemia, but it is initiated in pre-existing collateral vessels. Increased perfusion pressure and pulsatile blood shear stress induces diametrical growth via transient inflammatory response, including growth factors and cytokines such as tumour necrosis factor α.


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References

Cao Y (ed.): Angiogenesis in Adipose Tissue. Springer, 2013. doi: 10.1007/978-1-4614-8069-3.

Feige J-J, Pagès G, Soncin F (eds.): Molecular Mechanisms of Angiogenesis - From Ontogenesis to Oncogenesis. Springer, 2014. doi: 10.1007/978-2-8178-0466-8.

Figg WD, Folkman J (eds.): Angiogenesis - An Integrative Approach From Science to Medicine. Springer, 2008. doi: 10.1007/978-0-387-71518-6.

Haubner R, Beer AJ, Wang H, Chen X. Positron emission tomography tracers for imaging angiogenesis. Eur J Nucl Med Mol Imaging 2010; 37(Suppl 1): S86-S103.

Hendrikx G, Vöö S, Bauwens M, Post MJ, Mottaghy FM. SPECT and PET imaging of angiogenesis and arteriogenesis in pre-clinical models of myocardial ischemia and peripheral vascular disease. Eur J Nucl Med Mol Imaging 2016; 43: 2433-2447.

Hong H, Chen F, Zhang Y, Cai W. New radiotracers for imaging of vascular targets in angiogenesis-related disease. Adv Drug Deliv Rev. 2014; 76: 2-20.

Marcu R, Zheng Y, Hawkins BJ. Mitochondria and angiogenesis. Adv Exp Med Biol. 2017; 982: 371-406. doi: 10.1007/978-3-319-55330-6_21.

Mehta JL, Dhalla NS (eds.): Biochemical Basis and Therapeutic Implications of Angiogenesis. Springer, 2013. doi: 10.1007/978-1-4614-5857-9.

Ribatti D: Inflammation and Angiogenesis. Springer, 2017. 10.1007/978-3-319-68448-2.

Salajegheh A: Angiogenesis in Health, Disease and Malignancy. Springer, 2016. doi: 10.1007/978-3-319-28140-7.



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Created at: 2017-09-25
Updated at: 2018-08-09
Written by: Vesa Oikonen