Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography

Schnell, Oliver; Krebs, Bjarne; Carlsen, Janette; Miederer, Isabelle; Goetz, Claudia; Goldbrunner, Roland; Wester, Hans‐Jürgen; Haubner, Roland; Pöpperl, Gabriele; Holtmannspötter, Markus; Kretzschmar, Hans A.; Kessler, Horst; Tonn, Jörg‐Christian; Schwaiger, Markus; Beer, Ambros J.

doi:10.1215/15228517-2009-024

Cited by 182 publications

(123 citation statements)

References 24 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…2a). this is in contrast to observations noted in malignant gliomas by schnell et al (47) and in melanoma by albelda et al (48), who found that tumors expressed higher levels of αvβ3 than normal tissues. A statistically significant increased staining vs. controls was demonstrated for αvβ3 in endothelia, but not in stroma (tables iv and v).…”

Section: Discussioncontrasting

confidence: 99%

“…Other studies have found increased αvβ3 expression to be correlated with greater invasive or metastatic potential (53)(54)(55). Radiotracers specific to αvβ3 have revealed this integrin in human tumor tissue in situ (47,56). αvβ5 integrin has also been implicated in tumor cell invasion and migration (57)(58)(59), and αvβ3 and αvβ5 regulate cellular responses to hypoxia in glioblastomas (60).…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Immunohistochemical analysis of integrins αvβ3, αvβ5 and α5β1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas

Fabricius

Wildner

Kruse-Boitschenko

et al. 2010

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. integrins mediate the interaction of cells with the extracellular matrix and are believed to be involved in tumor cell survival and metastasis, and in tumor angiogenesis. We used immunohistochemistry of fresh-frozen human tumor tissues to analyze the presence of integrins αvβ3, αvβ5 and α5β1, which are believed to be involved in tumor growth and migration, together with integrin ligands, vitronectin, osteopontin, fibronectin and fibrinogen, in human oral squamous cell carcinomas. Samples of squamous cell carcinomas and control tissues from patients without cancer undergoing oral or maxillofacial surgery were frozen in liquid nitrogen within 30 min of removal. Frozen sections were prepared, and the presence of integrins or ligands was visualized using standard immunohistochemistry (apaap) with a blinded evaluation. comparison of samples from the 40 oral cancer patients and the 20 controls revealed increased staining in tumors compared with the controls, and staining was demonstrated for αvβ3 in endothelia. αvβ5 staining was increased in the tumor samples, but this was associated with increased expression in stroma rather than in endothelia. modestly increased expression of α5β1 was observed in the tumor samples, and this was associated with tumor cells, endothelia and stroma. Expression of ligands for the integrins varied between tissue types, with increased fibrinogen and fibronectin expression in tumor endothelia. Confirmation of the presence of these integrins and their association with tumor cells, endothelia or stroma suggests their potential for these integrins in human oral tumors. Overall, the increased expression of integrins within tumors, particularly expression associated with endothelial cells, supports the principle of selective integrin blockade as a novel anticancer strategy. IntroductionWorldwide, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (HNSCC) has not significantly increased for many years (1-5). HNSCC is diagnosed predominantly at the age range of 50-70 years, but is also observed in younger patients (6-8). despite aggressive initial management of the primary tumor, locoregional recurrence occurs in some 60% of cases, and distant metastasis is observed in some 25%. therefore, innovative therapeutic concepts are urgently required.angiogenesis is essential for tumor progression and metastasis. tumor angiogenesis is complex and involves crosstalk between tumor-derived growth factors, the modified extracellular matrix that develops around tumors, and endothelial receptors for extracellular matrix and growth factors (9,10). inhibition of angiogenesis often suppresses the tumor growth of model tumors, and the suppression and eradication of malignant tumors by targeting angiogenetic endothelial cells is a rapidly evolving approach to cancer therapy (10,11

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Immunohistochemical analysis of integrins αvβ3, αvβ5 and α5β1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas

Fabricius

Wildner

Kruse-Boitschenko

et al. 2010

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…c(RGDfK), a variant of the integrin antagonist Cilengitide, binds specifically to α v β 3 and α v β 5 integrins (33). c(RGDfK) was chosen for comparison because cyclic peptides containing an RGD motif have been evaluated as molecular imaging agents in numerous preclinical and clinical studies, including studies of human brain tumors (34). As with EETI 2.5F, these three peptides were labeled with AF680 such that one dye molecule was attached per peptide.…”

Section: Resultsmentioning

confidence: 99%

Engineered knottin peptide enables noninvasive optical imaging of intracranial medulloblastoma

Moore

Gephart

Bergen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Central nervous system tumors carry grave clinical prognoses due to limited effectiveness of surgical resection, radiation, and chemotherapy. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. We demonstrate that mouse cerebellar medulloblastoma (MB) can be targeted and illuminated with a fluorescent, engineered cystine knot (knottin) peptide that binds with high affinity to α v β 3 , α v β 5 , and α 5 β 1 integrin receptors. This integrin-binding knottin peptide, denoted EETI 2.5F, was evaluated as a molecular imaging probe in both orthotopic and genetic models of MB. Following tail vein injection, fluorescence arising from dye-conjugated EETI 2.5F was localized to the tumor compared with the normal surrounding brain tissue, as measured by optical imaging. The imaging signal intensity correlated with tumor volume. Due to its unique ability to bind to α 5 β 1 integrin, EETI 2.5F showed superior in vivo and ex vivo brain tumor imaging contrast compared with other engineered integrin-binding knottin peptides and with c(RGDfK), a well-studied integrin-binding peptidomimetic. Next, EETI 2.5F was fused to an antibody fragment crystallizable (Fc) domain (EETI 2.5F–Fc) to determine if a larger integrin-binding protein could also target intracranial brain tumors. EETI 2.5F–Fc, conjugated to a fluorescent dye, illuminated MB following i.v. injection and was able to distribute throughout the tumor parenchyma. In contrast, brain tumor imaging signals were not detected in mice injected with EETI 2.5F proteins containing a scrambled integrin-binding sequence, demonstrating the importance of target specificity. These results highlight the potential of using EETI 2.5F and EETI 2.5–Fc as targeted molecular probes for brain tumor imaging.

show abstract

“…We realize that antiangiogenic therapy is more commonly used in other tumor types such as glioblastoma and breast cancer. However, in these malignancies a v b 3 integrins are frequently expressed on the surface of endothelial cells and related tumor cells (16,17). Therefore, it is challenging to monitor antiangiogenic therapies in these tumor types with RGD peptides.…”

Section: Discussionmentioning

confidence: 99%

Does Imaging α_vβ₃ Integrin Expression with PET Detect Changes in Angiogenesis During Bevacizumab Therapy?

et al. 2014

View full text Add to dashboard Cite

Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography

Cited by 182 publications

References 24 publications

Immunohistochemical analysis of integrins αvβ3, αvβ5 and α5β1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas

Immunohistochemical analysis of integrins αvβ3, αvβ5 and α5β1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas

Engineered knottin peptide enables noninvasive optical imaging of intracranial medulloblastoma

Does Imaging α_vβ₃ Integrin Expression with PET Detect Changes in Angiogenesis During Bevacizumab Therapy?

Contact Info

Product

Resources

About

Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography

Cited by 182 publications

References 24 publications

Immunohistochemical analysis of integrins αvβ3, αvβ5 and α5β1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas

Immunohistochemical analysis of integrins αvβ3, αvβ5 and α5β1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas

Engineered knottin peptide enables noninvasive optical imaging of intracranial medulloblastoma

Does Imaging αvβ3 Integrin Expression with PET Detect Changes in Angiogenesis During Bevacizumab Therapy?

Contact Info

Product

Resources

About

Does Imaging α_vβ₃ Integrin Expression with PET Detect Changes in Angiogenesis During Bevacizumab Therapy?