Marta de Souza Albernaz1,2,3, Sergio Hiroshi Toma3, Jeff Clanton2,4, Koiti Araki5, Ralph Santos-Oliveira6,7. 1. Radiopharmacy Service, University Hospital Clementino Fraga Filho, Rio de Janeiro, Brazil. 2. Instituto de Pesquisas Energéticas e Nucleares, Centro de Radiofarmácia, São Paulo, Brazil. 3. Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, SP, 05508-000, Brazil. 4. Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 5. Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, SP, 05508-000, Brazil. koiaraki@iq.usp.br. 6. Instituto de Pesquisas Energéticas e Nucleares, Centro de Radiofarmácia, São Paulo, Brazil. roliveira@ien.gov.br. 7. Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil. roliveira@ien.gov.br.
Abstract
PURPOSE: In this study we developed and tested an iron oxide nanoparticle conjugated with DTPA and Trastuzumab, which can efficiently be radiolabeled with 99m-Tc and Ga-68, generating a nanoradiopharmaceutical agent to be used for SPECT and PET imaging. METHODS: The production of iron oxide nanoparticle conjugated with DTPA and Trastuzumab was made using phosphorylethanolamine (PEA) surface modification. Both radiolabeling process was made by the direct radiolabeling of the nanoparticles. The in vivo assay was done in female Balb/c nude mice xenografted with breast cancer. Also a planar imaging using the radiolabeled nanoparticle was performed. RESULTS: No thrombus and immune response leading to unwanted interaction and incorporation of nanoparticles by endothelium and organs, except filtration by the kidneys, was observed. In fact, more than 80% of 99mTc-DTPA-TZMB@Fe3O4 nanoparticles seems to be cleared by the renal pathway but the implanted tumor whose seems to increase the expression of HER2 receptors enhancing the uptake by all other organs. CONCLUSION: However, even in this unfavorable situation the tumor bioconcentrated much larger amounts of the nano-agent than normal tissues giving clear enough contrast for breast cancer imaging for diagnostics purpose by both SPECT and PET technique. Graphical Abstract ᅟ.
PURPOSE: In this study we developed and tested an iron oxide nanoparticle conjugated with DTPA and Trastuzumab, which can efficiently be radiolabeled with 99m-Tc and Ga-68, generating a nanoradiopharmaceutical agent to be used for SPECT and PET imaging. METHODS: The production of iron oxide nanoparticle conjugated with DTPA and Trastuzumab was made using phosphorylethanolamine (PEA) surface modification. Both radiolabeling process was made by the direct radiolabeling of the nanoparticles. The in vivo assay was done in female Balb/c nude mice xenografted with breast cancer. Also a planar imaging using the radiolabeled nanoparticle was performed. RESULTS: No thrombus and immune response leading to unwanted interaction and incorporation of nanoparticles by endothelium and organs, except filtration by the kidneys, was observed. In fact, more than 80% of 99mTc-DTPA-TZMB@Fe3O4 nanoparticles seems to be cleared by the renal pathway but the implanted tumor whose seems to increase the expression of HER2 receptors enhancing the uptake by all other organs. CONCLUSION: However, even in this unfavorable situation the tumor bioconcentrated much larger amounts of the nano-agent than normal tissues giving clear enough contrast for breast cancer imaging for diagnostics purpose by both SPECT and PET technique. Graphical Abstract ᅟ.
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