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Development of Ga-68 labeled, biotinylated thiosemicarbazone dextran-coated iron oxide nanoparticles as multimodal PET/MRI probe.

Abstract
Bifunctional biotinylated thiosemicarbazone dextran-coated iron oxide Nanoparticles (NPs) were fabricated. Aldehyde groups of the oxidized dextran-coating layer were utilized to conjugate biotin as a tumor-targeting agent and thiosemicarbazide as a cation chelator on the surface of NPs. The final product was characterized for physicochemical and biological properties. It was compatible with red blood cells and did not change the blood coagulation time. It also showed a significantly enhanced affinity to biotin receptor-positive 4T1 cells compared to non-biotinylated ones. The r2 relaxivity coefficient value of the final product was 110.2 mM-1 s-1. Although biotinylated NPs were easily radiolabeled with Ga-68 at room temperature, the stable radiolabeled NPs were achieved at a higher temperature (60 °C). The radiolabeled NPs were majorly accumulated in the liver and spleen. However, about 5.4% ID/g of the radiolabeled NPs was accumulated within the 4T1 tumor site. Blocking studies was performed by the biotin molecules pre-injection showed uptake reduction in the 4T1 tumor (about 1.1% ID/g). The radiolabeled NPs could be used for the early detection of biotin receptor-positive tumors via PET-MRI.
AuthorsNazila Gholipour, Mehdi Akhlaghi, Amin Mokhtari Kheirabadi, Parham Geramifar, Davood Beiki
JournalInternational journal of biological macromolecules (Int J Biol Macromol) Vol. 148 Pg. 932-941 (Apr 01 2020) ISSN: 1879-0003 [Electronic] Netherlands
PMID31981670 (Publication Type: Journal Article)
CopyrightCopyright © 2020 Elsevier B.V. All rights reserved.
Chemical References
  • Dextrans
  • Ferric Compounds
  • Gallium Radioisotopes
  • Thiosemicarbazones
  • ferric oxide
  • Biotin
  • Gallium-68
Topics
  • Animals
  • Biotin
  • Cell Line, Tumor
  • Cell Survival
  • Dextrans (chemistry)
  • Disease Models, Animal
  • Ferric Compounds (chemistry)
  • Fibrosarcoma (diagnostic imaging, pathology)
  • Gallium Radioisotopes (chemistry)
  • Heterografts
  • Humans
  • Magnetic Resonance Imaging
  • Metal Nanoparticles (chemistry)
  • Mice
  • Positron Emission Tomography Computed Tomography
  • Positron-Emission Tomography
  • Thiosemicarbazones (chemistry)

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