Acetylated, DOTA armed, PAMAM dendrimer coated Fe3O4 Fabrication, characterization, 68Ga Radiolabeling and Primary Biological Evaluation

Background: Multifunctional nanoparticles (NPs) were recently interested for the use in multimodal imaging systems such as PET-MRI, PET-CT, PET-OI and etc. In this work, a Fe3O4@PAMAM@DOTA@ Ac NPs as PET-MRI agent was fabricated, characterized and radiolabeled with Ga-68 PET radioisotope.Methods: Fe3O4 NPs (SP) was prepared by co-precipitation of Fe2+ and Fe3+ and then coated with G4 generation PAMAM follow by functionalization with DOTA. Finally, the free amine groups on the NPs surface were acetylated. The nanoparticles were characterized by the FT-IR, TGA, MTT, coagulation and hemolysis assay, TEM, XRD, CHNS, DLS and Zeta potential. The nanoparticle was radiolabeled with Ga-68 radioisotope and controlled for radiolabeling yield by Radio-TLC. The stability of radiolabeled nanoparticle was checked in cysteine solution and fresh serum. Finally, the radiolabeled nanoparticle was intravenously administrated to the fibrosarcoma bearing animal model and the biodistribution profile was determined.Results: FT-IR spectrums confirmed the formation of net NPs and all coating and modification steps. TGA profiles confirmed the step-ward increase in the organic content. TEM images outlined 13±5 nm size distribution. However, the DLS size and Zeta potentials depended on the quantity of DOTA. Acetylation specifically decreased the aggregation effect as well as the cytotoxicity effect on Hella cell line and increased blood compatibility. Although, the SP@G4PAMAM was radiolabeled with Ga-68, but a stable radiolabeled NPs was obtained with DOTA armed NPs which shown an uptake in cancerous tissue.Conclusion: The radiolabeled Fe3O4@G4PAMAM@DOTA@Ac NPs successfully radiolabeled and could be used for multimodal PET-MRI imaging.

Acetylated, DOTA armed, PAMAM dendrimer coated Fe3O4 Fabrication, characterization, 68Ga Radiolabeling and Primary Biological Evaluation Keywords:

Fe3O4 nanoparticle , PAMAM , PET-MRI