title: Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines.
abstract: The clinical value of current and future nanomedicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines such as liposomal drugs with PET radionuclides will have a wide impact in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling method that exploits the metal-chelating properties of certain drugs (e.g., bisphosphonates such as alendronate and anthracyclines such as doxorubicin) and widely used ionophores to achieve excellent radiolabeling yields, purities, and stabilities with89Zr,52Mn, and64Cu, and without the requirement of modification of the nanomedicine components. In a model of metastatic breast cancer, we demonstrate that this technique allows quantification of the biodistribution of a radiolabeled stealth liposomal nanomedicine containing alendronate that shows high uptake in primary tumors and metastatic organs. The versatility, efficiency, simplicity, and GMP compatibility of this method may enable submicrodosing imaging studies of liposomal nanomedicines containing chelating drugs in humans and may have clinical impact by facilitating the introduction of image-guided therapeutic strategies in current and future nanomedicine clinical studies.
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.
authors: Scott
authors: S
authors: Edmonds
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.
authors: Alessia
authors: A
authors: Volpe
authors: Oncology Institute, Shaare Zedek Medical Center and Hebrew University-School of Medicine , Jerusalem 9103102, Israel.
authors: Hilary
authors: H
authors: Shmeeda
authors: Division of Cancer Studies, King's College London , London SE1 1UL, United Kingdom.
authors: Ana C
authors: AC
authors: Parente-Pereira
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.|Department of Chemistry, King's College London , London SE1 1DB, United Kingdom.
authors: Riya
authors: R
authors: Radia
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.
authors: Julia
authors: J
authors: Baguña-Torres
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.
authors: Istvan
authors: I
authors: Szanda
authors: The Hevesy Lab, Technical University of Denmark , 4000 Roskilde, Denmark.
authors: Gregory W
authors: GW
authors: Severin
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.
authors: Lefteris
authors: L
authors: Livieratos
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.
authors: Philip J
authors: PJ
authors: Blower
authors: Division of Cancer Studies, King's College London , London SE1 1UL, United Kingdom.
authors: John
authors: J
authors: Maher
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.
authors: Gilbert O
authors: GO
authors: Fruhwirth
authors: Oncology Institute, Shaare Zedek Medical Center and Hebrew University-School of Medicine , Jerusalem 9103102, Israel.
authors: Alberto
authors: A
authors: Gabizon
authors: Division of Imaging Sciences & Biomedical Engineering, King's College London , London SE1 7EH, United Kingdom.
authors: Rafael
authors: R
authors: T M de Rosales
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging; D003301:Copper Radioisotopes; D005260:Female; D006801:Humans; D008081:Liposomes; D008345:Manganese; D050997:Nanomedicine; D049268:Positron-Emission Tomography; D011868:Radioisotopes; D014018:Tissue Distribution; D015040:Zirconium
chemical_list: D003301:Copper Radioisotopes; C000615411:Copper-64; D008081:Liposomes; C000615377:Manganese-52; D011868:Radioisotopes; D008345:Manganese; D015040:Zirconium; C000615502:Zirconium-89
keywords: PET imaging; drug delivery; liposomes; metastasis; nanomedicine; tumor