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Bioluminescence Imaging of an Immunocompetent Animal Model for Glioblastoma
Published on: January 15, 2016
A new optical imaging probe targeting αVβ3 integrin in glioblastoma xenografts
Stefania Lanzardo1, Laura Conti, Chiara Brioschi
1Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Abstract:
α(V)β(3) Integrins are a widely recognized target for in vivo molecular imaging of pathological conditions such as inflammation, cancer and rheumatoid arthritis. We have evaluated the sensitivity of a new, near-infrared fluorescence (NIRF), RGD cyclic probe (DA364) in noninvasive detection of α(V) β(3) integrin-overexpressing tumors. DA364's binding affinity for α(V)β(3) integrin was first evaluated in vitro. Human α(V)β(3) integrin-positive, U-87 MG glioblastoma cells were then xenografted in nude mice, and DA364 was injected intravenously (i.v.) to evaluate its in vivo distribution, specificity and sensitivity in comparison with a commercially available probe. DA364 bound α(V)β(3) integrin on U-87 MG cells with high affinity and specificity, both in vitro and in vivo. This binding specificity was corroborated by the strong inhibition of its tumor uptake induced by nonfluorescent, cyclic-RGD peptides. Ex vivo analysis showed that DA364 accumulated at the tumor site, whereas very low levels were detected in liver and spleen. In conclusion, DA364 allows sensitive and specific detection of transplantable glioblastoma by NIRF imaging, and is thus a promising candidate for the elaboration of imaging and therapeutic probes for α(V)β(3) integrin-overexpressing tumors.
Insights
A new near-infrared fluorescence (NIRF) probe, DA364, effectively detects alpha(V)beta(3) integrin-overexpressing tumors. This probe shows high affinity and specificity for glioblastoma detection via noninvasive imaging.
Area of Science:
- Molecular Imaging
- Biomedical Engineering
- Oncology
Background:
- Alpha(V)beta(3) integrins are key targets for imaging pathological conditions like cancer.
- Noninvasive molecular imaging requires sensitive and specific probes for early disease detection.
Purpose of the Study:
- To evaluate the sensitivity and specificity of a novel near-infrared fluorescence (NIRF) RGD cyclic probe, DA364.
- To assess DA364's potential for noninvasive detection of alpha(V)beta(3) integrin-overexpressing tumors.
Main Methods:
- In vitro binding affinity assays of DA364 for alpha(V)beta(3) integrin.
- In vivo studies using U-87 MG glioblastoma xenografts in nude mice.
- Comparison of DA364 with a commercial probe for tumor uptake, distribution, and specificity.
Main Results:
- DA364 demonstrated high affinity and specificity for alpha(V)beta(3) integrin on U-87 MG cells.
- Tumor uptake of DA364 was significantly inhibited by nonfluorescent cyclic-RGD peptides, confirming specificity.
- Ex vivo analysis revealed DA364 accumulation at the tumor site with minimal uptake in liver and spleen.
Conclusions:
- DA364 enables sensitive and specific detection of transplantable glioblastoma using NIRF imaging.
- DA364 is a promising candidate for developing advanced imaging and therapeutic agents targeting alpha(V)beta(3) integrin.
- The probe's performance supports its utility in preclinical cancer research and diagnostics.
