scholarly journals Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status

2021 ◽  
Vol 22 (11) ◽  
pp. 5544
Author(s):  
Alexandru Florea ◽  
Felix M. Mottaghy ◽  
Matthias Bauwens
Keyword(s):  
Molecular Imaging ◽  
Clinical Status ◽  
Tumour Microenvironment ◽  
Vascular Endothelial ◽  
Vessel Growth ◽  
Pubmed Search ◽  
Direct Targeting ◽  
Survival And Growth ◽  
Tumour Vascularisation ◽  
Endothelial Growth Factor

Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine.

Taming of the wild vessel: promoting vessel stabilization for safe therapeutic angiogenesis

2011 ◽  
Vol 39 (6) ◽  
pp. 1654-1658 ◽  
Author(s):  
Silvia Reginato ◽  
Roberto Gianni-Barrera ◽  
Andrea Banfi
Keyword(s):  
Current Knowledge ◽  
Single Gene ◽  
Therapeutic Angiogenesis ◽  
Maturation Stage ◽  
Vascular Endothelial ◽  
Cellular Regulation ◽  
Vessel Growth ◽  
Vascular Structures ◽  
Endothelial Growth Factor ◽  
Vascular Maturation

VEGF (vascular endothelial growth factor) is the master regulator of blood vessel growth. However, it displayed substantial limitations when delivered as a single gene to restore blood flow in ischaemic conditions. Indeed, uncontrolled VEGF expression can easily induce aberrant vascular structures, and short-term expression leads to unstable vessels. Targeting the second stage of the angiogenic process, i.e. vascular maturation, is an attractive strategy to induce stable and functional vessels for therapeutic angiogenesis. The present review discusses the limitations of VEGF-based gene therapy, briefly summarizes the current knowledge of the molecular and cellular regulation of vascular maturation, and describes recent pre-clinical evidence on how the maturation stage could be targeted to achieve therapeutic angiogenesis.

scholarly journals Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Junko Yoshida ◽  
Robert T. Wicks ◽  
Andrea I. Zambrano ◽  
Betty M. Tyler ◽  
Kashi Javaherian ◽  
...  
Keyword(s):  
Angiogenesis Inhibitor ◽  
Corneal Neovascularization ◽  
Subconjunctival Injection ◽  
Vascular Endothelial ◽  
Vessel Length ◽  
Treatment Groups ◽  
Significant Difference ◽  
Vessel Growth ◽  
Endothelial Growth Factor ◽  
Clinical Potential

We assessed the antiangiogenic effects of subconjunctival injection of Fc-endostatin (FcE) using a human vascular endothelial growth factor-induced rabbit corneal neovascularization model. Angiogenesis was induced in rabbit corneas through intrastromal implantations of VEGF polymer implanted 2 mm from the limbus. NZW rabbits were separated into groups receiving twice weekly subconjunctival injections of either saline; 25 mg/mL bevacizumab; 2 mg/mL FcE; or 20 mg/mL FcE. Corneas were digitally imaged at 5 time points. An angiogenesis index (AI) was calculated (vessel length (mm) × vessel number score) for each observation. All treatment groups showed a significant decrease in the vessel length and AI compared to saline on all observation days (P<0.001). By day 15, FcE 2 inhibited angiogenesis significantly better than FcE 20 (P<0.01). There was no significant difference between FcE 2 and BV, although the values trended towards significantly increased inhibition by BV. BV was a significantly better inhibitor than FcE 20 by day 8 (P<0.01). FcE was safe and significantly inhibited new vessel growth in a rabbit corneal neovascularization model. Lower concentration FcE 2 exhibited better inhibition than FcE 20, consistent with previous FcE studies referencing a biphasic dose-response curve. Additional studies are necessary to further elucidate the efficacy and clinical potential of this novel angiogenesis inhibitor.

scholarly journals Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth

2009 ◽  
Vol 106 (17) ◽  
pp. 7137-7142 ◽  
Author(s):  
Won Gil Cho ◽  
Romulo J. C. Albuquerque ◽  
Mark E. Kleinman ◽  
Valeria Tarallo ◽  
Adelaide Greco ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Mouse Models ◽  
Tissue Injury ◽  
Vascular Endothelial ◽  
Small Interfering Rnas ◽  
Vessel Growth ◽  
Interfering Rna ◽  
Endothelial Growth Factor ◽  
Tlr3 Activation

Neovascularization in response to tissue injury consists of the dual invasion of blood (hemangiogenesis) and lymphatic (lymphangiogenesis) vessels. We reported recently that 21-nt or longer small interfering RNAs (siRNAs) can suppress hemangiogenesis in mouse models of choroidal neovascularization and dermal wound healing independently of RNA interference by directly activating Toll-like receptor 3 (TLR3), a double-stranded RNA immune receptor, on the cell surface of blood endothelial cells. Here, we show that a 21-nt nontargeted siRNA suppresses both hemangiogenesis and lymphangiogenesis in mouse models of neovascularization induced by corneal sutures or hindlimb ischemia as efficiently as a 21-nt siRNA targeting vascular endothelial growth factor-A. In contrast, a 7-nt nontargeted siRNA, which is too short to activate TLR3, does not block hemangiogenesis or lymphangiogenesis in these models. Exposure to 21-nt siRNA, which we demonstrate is not internalized unless cell-permeating moieties are used, triggers phosphorylation of cell surface TLR3 on lymphatic endothelial cells and induces apoptosis. These findings introduce TLR3 activation as a method of jointly suppressing blood and lymphatic neovascularization and simultaneously raise new concerns about the undesirable effects of siRNAs on both circulatory systems.

scholarly journals Implications of Vascular Endothelial Growth Factor for Postischemic Neurovascular Remodeling

2009 ◽  
Vol 29 (10) ◽  
pp. 1620-1643 ◽  
Author(s):  
Dirk Matthias Hermann ◽  
Anil Zechariah
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Brain Plasticity ◽  
Brain Perfusion ◽  
Therapeutic Angiogenesis ◽  
Vascular Endothelial ◽  
Neurologic Recovery ◽  
Vessel Growth ◽  
Neurovascular Remodeling ◽  
Endothelial Growth Factor

Neurovascular remodeling has been recently recognized as a promising target for neurologic therapies. Hopes have emerged that, by stimulating vessel growth, it may be possible to stabilize brain perfusion, and at the same time promote neuronal survival, brain plasticity, and neurologic recovery. In this review, we outline the role of vascular endothelial growth factor (VEGF) in the ischemic brain, analyzing how this growth factor contributes to brain remodeling. Studies with therapeutic VEGF administration resulted in quite variable results depending on the route and time point of delivery. Local VEGF administration consistently enhanced neurologic recovery, whereas acute intravenous delivery exacerbated brain infarcts due to enhanced brain edema. Future studies should answer the following questions: (1) whether increased vessel density translates into improvements in blood flow in the hemodynamically compromised brain; (2) how VEGF influences brain plasticity and contributes to motor and nonmotor recovery; (3) what are the actions of VEGF not only in young animals with preserved vasculature, on which previous studies have been conducted, but also in aged animals and in animals with preexisting atherosclerosis; and (4) whether the effects of VEGF can be mimicked by pharmacological compounds or by cell-based therapies. Only on the basis of such information can more definite conclusions be made with regard to whether the translation of therapeutic angiogenesis into clinics is promising.

scholarly journals Human endometrial angiogenesis

Reproduction ◽  
2001 ◽  
pp. 181-186 ◽  
Author(s):  
CE Gargett ◽  
PA Rogers
Keyword(s):  
Strong Relationship ◽  
Human Endometrium ◽  
Endothelial Cell Proliferation ◽  
Microvascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Proliferative Phase ◽  
Vessel Growth ◽  
Capillary Plexus ◽  
Reproductive Life ◽  
Endothelial Growth Factor

Angiogenesis is the development of new microvessels from existing vessels, a process that involves microvascular endothelial cells. Physiological angiogenesis rarely occurs in adults except in the ovary and endometrium during the reproductive life of females. Angiogenesis occurs by sprouting and non-sprouting mechanisms. Since endothelial sprouts are not observed in human endometrium, we hypothesized that non-sprouting mechanisms such as intussusception and elongation are involved in endometrial angiogenesis. The demand for angiogenesis differs spatially and temporally in the endometrium: angiogenesis occurs in the basalis layer during menstruation and in the functionalis and subepithelial capillary plexus during the proliferative and early secretory stages. Most studies have failed to demonstrate a link between expression of endometrial angiogenic factors and new vessel growth. However, we demonstrated recently a strong relationship between vascular endothelial growth factor (VEGF) immunolocalized in in-travascular neutrophils and endothelial cell proliferation in each of the subepithelial capillary plexus, functionalis and basalis regions of the human endometrium. Our data also indicate that focal neutrophil VEGF has a role in the development of the subepithelial capillary plexus and functionalis microvessels during the proliferative phase of the menstrual cycle. We propose that neutrophils are an intravascular source of VEGF for vessels that undergo angiogenesis by intussusception and elongation.

scholarly journals Hydroxyestrogens inhibit angiogenesis in swine ovarian follicles

2008 ◽  
Vol 199 (1) ◽  
pp. 127-135 ◽  
Author(s):  
G Basini ◽  
S Bussolati ◽  
S E Santini ◽  
F Bianchi ◽  
M Careri ◽  
...  
Keyword(s):  
Follicular Fluid ◽  
Ovarian Follicle ◽  
Negative Control ◽  
Follicle Development ◽  
Vascular Endothelial ◽  
Angiogenic Potential ◽  
Vessel Growth ◽  
Negative Effect ◽  
Endothelial Growth Factor ◽  
Lines Of Evidence

The rapid, controlled, and cyclical nature of angiogenesis in the ovarian follicle suggests the potential for sex steroids to influence neovascularization. Angiogenesis is regulated by a local balance between the levels of endogenous stimulators and inhibitors. Multiple lines of evidence suggest that estrogens stimulate angiogenesis via effects on endothelial cells. However, it is of outstanding value to investigate the negative control of this process. Since the main estrogen metabolites, 2-hydroxyestradiol and 4-hydroxyestradiol (4-OHE2) have been demonstrated to function as anti-estrogen in several estrogen-dependent organs; the aim of this study was to investigate their potential involvement in the modulation of follicular angiogenesis. Hydroxyestrogens were quantified in swine follicular fluid and their effects were studied on granulosa cell vascular endothelial growth factor (VEGFA) production and tested in an angiogenesis bioassay. Our study documents that these molecules are physiologically present in swine follicular fluid and their concentrations significantly (P<0.001) increase during follicle development. Moreover, angiogenesis bioassay revealed that both hydroxyestrogens significantly (P<0.001) inhibited new vessel growth. We evidenced that the most potent negative effect is mediated by 4-OHE2. The anti-angiogenic potential of this molecule is also supported by its ability to inhibit (P<0.001) VEGFA production by granulosa cells. Increased knowledge in this area is of utmost importance for future therapeutic options to contrast infertility disorders associated with aberrant angiogenesis; this would be also very useful for the treatment of diseases characterized by disregulated angiogenesis and vascular regression.

scholarly journals Split for the cure: VEGF, PDGF-BB and intussusception in therapeutic angiogenesis

2014 ◽  
Vol 42 (6) ◽  
pp. 1637-1642 ◽  
Author(s):  
Roberto Gianni-Barrera ◽  
Mariateresa Bartolomeo ◽  
Brigitte Vollmar ◽  
Valentin Djonov ◽  
Andrea Banfi
Keyword(s):  
Growth Factor ◽  
Therapeutic Angiogenesis ◽  
Therapeutic Benefit ◽  
Vascular Endothelial ◽  
Therapeutic Implications ◽  
Vascular Growth ◽  
Intussusceptive Angiogenesis ◽  
Vessel Growth ◽  
Endothelial Growth Factor

Therapeutic angiogenesis is an attractive strategy to treat patients suffering from ischaemic conditions and vascular endothelial growth factor-A (VEGF) is the master regulator of blood vessel growth. However, VEGF can induce either normal or aberrant angiogenesis depending on its dose localized in the microenvironment around each producing cell in vivo and on the balanced stimulation of platelet-derived growth factor-BB (PDGF-BB) signalling, responsible for pericyte recruitment. At the doses required to induce therapeutic benefit, VEGF causes new vascular growth essentially without sprouting, but rather through the alternative process of intussusception, or vascular splitting. In the present article, we briefly review the therapeutic implications of controlling VEGF dose on one hand and pericyte recruitment on the other, as well as the key features of intussusceptive angiogenesis and its regulation.

Sign in / Sign up

Export Citation Format

Share Document