Biocompatible nanocomposite for PET/MRI hybrid imaging

Erica Locatelli,¹ Larraitz Gil,² Liron Limor Israel,³ Lorena Passoni,^4,5 Maria Naddaka,¹ Andrea Pucci,¹ Torsten Reese,⁶ Vanessa Gomez-Vallejo,² Paolo Milani,^5,7 Michela Matteoli,^4,8 Jordi Llop,² Jean Paul Lellouche,³ Mauro Comes Franchini<sup>1

1</sup>Department of Industrial Chemistry “Toso Montanari”. University of Bologna, Italy; ²Radiochemistry Department, Molecular Imaging Unit, CIC biomaGUNE, San Sebastián, Guipúzcoa, Spain; ³Department of Chemistry, Nanomaterials Research Centre, Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel; ⁴Department of Medical Biotechnology and Translational Medicine, University of Milano, Italy; ⁵Fondazione Filarete, Milano, Italy; ⁶Imaging Department, Molecular Imaging Unit, CIC biomaGUNE, San Sebastián, Guipúzcoa, Spain; ⁷CIMAINA and Department of Physics, University of Milano, Italy; ⁸Humanitas Clinical and Research Center, Rozzano, Italy

Abstract: A novel nanocarrier system was designed and developed with key components uniquely structured at the nanoscale for early cancer diagnosis and treatment. In order to perform magnetic resonance imaging, hydrophilic superparamagnetic maghemite nanoparticles (NPs) were synthesized and coated with a lipophilic organic ligand. Next, they were entrapped into polymeric NPs made of biodegradable poly(lactic-co-glycolic acid) linked to polyethylene glycol. In addition, resulting NPs have been conjugated on their surface with a 2,2'-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ligand for subsequent ⁶⁸Ga incorporation. A cell-based cytotoxicity assay has been employed to verify the in vitro cell viability of human pancreatic cancer cells exposed to this nanosystem. Finally, in vivo positron emission tomography-computerized tomography biodistribution studies in healthy animals were performed.

Keywords: maghemite nanoparticles, organic coating, polymeric nanoparticles, magnetic resonance imaging, radiolabeling, positron emission tomography

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