AI Article Synopsis

  • - α(V)β(3) integrins are key targets for imaging diseases like cancer and inflammation; a new near-infrared fluorescence probe, DA364, has been developed for detecting these integrins in tumors.
  • - DA364 demonstrated high binding affinity and specificity to α(V)β(3) integrin by being tested in human glioblastoma cells both in lab settings and in live mice, showing effective tumor targeting.
  • - The probe proved to be sensitive and specific in detecting glioblastoma, accumulating mainly at tumor sites and paving the way for potential imaging and treatment applications in similar cancer types.

Article 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.

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http://dx.doi.org/10.1002/cmmi.444DOI Listing

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