Decorated Superparamagnetic Iron Oxide Nanoparticles with Monoclonal Antibody and Diethylene-Triamine-Pentaacetic Acid Labeled with Thechnetium-99m and Galium-68 for Breast Cancer Imaging
- 308 Downloads
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.
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.
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.
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.
KEY WORDSimaging nanoradiopharmaceuticals oncology smart device
Iron oxide nanoparticles
Technetium 99 metastable
Invasive ductal carcinoma cell line
Diethylene triamine pentaacetic acid
- Ge68– Ga68
Germanium 68 – Gallium-68
Gastrointestinal stromal tumor
- HER2 receptors
Human epidermal growth factor receptor 2
Instant Thin Layer Chromatography – Silica Gel
Positron Emission Tomography
Regions of interest
Roswell Park Memorial Institute médium
Single Photon Emission Computed Tomography
Superparamagnetic iron oxide nanoparticles
Transmission Electron Microscopy
ACKNOWLEDGMENTS AND DISCLOSURES
Authors thankfully acknowledge Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for the financial support.
- 4.Bordim A, Patricio BFC, Sarcinelli MA, Albernaz MS, Santos-Oliveira R. Nanoradiopharmaceuticals: development of labeling process for polymeric nanoparticles. Anal Oncol. 2013;2(1):30–3.Google Scholar
- 6.Bretcanu O, Miola M, Bianchi CL, Marangi I, Carbone R, Corazzari I, et al. In vitro biocompatibility of a ferrimagnetic glass-ceramic for hyperthermia application. Mater Sci Eng C Mater Biol Appl. 2017;73:778–787. https://doi.org/10.1016/j.msec.2016.12.105.
- 12.Gao H, Liu X, Tang W, Niu D, Zhou B, Zhang H, et al. 99mTc-conjugated manganese-based mesoporous silica nanoparticles for SPECT, pH-responsive MRI and anti-cancer drug delivery. Nano. 2016;8(47):19573–80.Google Scholar
- 18.Ligiero TB, Cerqueira-Coutinho C, Albernaz MS, Szwed M, Bernardes ES, Wasserman MAV, et al. Diagnosing gastrointestinal stromal tumours by single photon emission computed tomography using nanoradiopharmaceuticals based on bevacizumab monoclonal antibody. Biomed Phys Eng Express. 2016;2(4):045017.CrossRefGoogle Scholar
- 20.Lub-de Hooge MN, Kosterink JG, Perik PJ, Nijnuis H, Tran L, Bart J, et al. Preclinical characterisation of 111IN-DTPA-trastuzumab. Br J Radiol. 2004;143:99–106.Google Scholar
- 23.Nasr SH, Kouyoumdjian H, Mallett C, Ramadan S, Zhu DC, Shapiro EM, et al. Detection of β-amyloid by sialic acid coated bovine serum albumin magnetic nanoparticles in a mouse model of Alzheimer's Disease. Small. 2017. https://doi.org/10.1002/smll.201701828.
- 30.Rosa TG, Dos Santos SN, De Jesus Andreoli Pinto T, DDM G, Barja-Fidalgo TC, Ricci-Junior E, et al. Microradiopharmaceutical for metastatic melanoma. Pharm Res. 2017; https://doi.org/10.1007/s11095-017-2275-3.
- 32.Sarcinelli MA, Albernaz MS, Szwed M, Iscaife A, Leite KR, Junqueira MS, et al. Nanoradiopharmaceuticals for breast cancer imaging: development, characterization, and imaging in inducted animals. OncoTargetsTher. 2016;23(9):5847–54.Google Scholar
- 39.Uchiyama MK, Toma SH, Cardoso RM, Rodrigues SF, Shimada ALB, Loiola RA, et al. Nanoparticles and their use as MRI contrast agent, BR102015013031–7, 08/06/2015.Google Scholar
- 40.Urban LABD, Chala LF, Bauab SDP, Schaefer MB, Dos Santos RP, Maranhão NMA, et al. Breast cancer screening: updated recommendations of the Brazilian College of Radiology and Diagnostic Imaging, Brazilian Breast Disease Society, and Brazilian Federation of Gynecological and Obstetrical Associations. Radiol Bras. 2017;50(4):244–9.CrossRefPubMedPubMedCentralGoogle Scholar