Does imaging αvβ3 integrin expression with PET detect changes in angiogenesis during bevacizumab therapy?

Abstract

UNLABELLED:

In recent years, there has been a growing interest in molecular imaging markers of tumor-induced angiogenesis. Several radiolabeled RGD (arginine, glycine, aspartate) peptides have been developed for PET imaging of αvβ3 integrins in the tumor vasculature, but there are only limited data on how angiogenesis inhibitors affect the tumor uptake of these peptides.

METHODS:

Changes in (68)Ga-NODAGA-c(RGDfK) peptide uptake were measured using PET during bevacizumab therapy of 2 αvβ3-negative squamous cell carcinoma cell lines (A-431 and FaDu) that induce αvβ3-positive neovasculature when transplanted into nude mice. Tumor uptake of (68)Ga-NODAGA-c(RGDfK) was correlated to microvascular density, vascular morphology, and permeability as well as αvβ3 integrin expression.

RESULTS:

Bevacizumab significantly inhibited growth of A-431 tumors and caused a significant reduction in microvascular density and αvβ3 integrin expression within 7 d after start of therapy. Bevacizumab also caused a normalization of blood vessel morphology and decreased tumor necrosis. However, (68)Ga-NODAGA-c(RGDfK) uptake was significantly increased at day 7 of therapy and did not decrease until after 3 wk of treatment. In Fadu xenografts, bevacizumab therapy caused only a minor inhibition of tumor growth and minor changes in (68)Ga-NODAGA-c(RGDfK) uptake.

CONCLUSION:

Uptake of radiolabeled RGD peptides is not necessarily decreased by effective antiangiogenic therapy. Early in the course of therapy a decrease in the expression of αvβ3 integrins may not be reflected by a decrease in the uptake of RGD peptides.

• Authors: Svetlana N Rylova, Enikö Barnucz, Melpomeni Fani, Friederike Braun, Martin Werner, Silke Lassmann, Helmut R Maecke, Wolfgang A Weber
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 55 Issue 11 Pg. 1878-84 (Nov 2014) ISSN: 1535-5667 [Electronic] United States
• PMID: 25278514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
• Acetates
• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Gallium Radioisotopes
• Heterocyclic Compounds, 1-Ring
• Integrin alphaVbeta3
• Oligopeptides
• Peptides
• Bevacizumab
• arginyl-glycyl-aspartic acid

Topics

• Acetates
• Algorithms
• Angiogenesis Inhibitors (chemistry)
• Animals
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Bevacizumab
• Carcinoma, Squamous Cell (diagnostic imaging, drug therapy)
• Cell Line, Tumor
• Female
• Gallium Radioisotopes (chemistry)
• Heterocyclic Compounds, 1-Ring
• Humans
• Integrin alphaVbeta3 (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microcirculation
• Necrosis
• Neoplasm Transplantation
• Neovascularization, Pathologic
• Oligopeptides (chemistry)
• Peptides (chemistry)
• Permeability
• Positron-Emission Tomography
• Time Factors