title: A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).
abstract: Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia among adults. Despite its indolent nature, CLL remains an incurable disease. Herein we aimed to monitor CLL disease engraftment and, progression/regression in a xenograft CLL mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI). Spleen contrast enhancement, quantified as percentage change in signal intensity upon USPIO administration, demonstrated a difference due to a reduced USPIO uptake, in the spleens of mice injected with CLL cells (NSG-CLL, n=71) compared to controls (NSG-CTR, n=17). These differences were statistically significant both after 2 and 4weeks from CLL cells injection. In addition comparison of mice treated with rituximab with untreated controls for changes in spleen iron uptake confirmed that it is possible to monitor treatment efficacy in this mouse model of CLL using USPIO-enhanced MRI. Further applications could include the preclinical in vivo monitoring of new therapies and the clinical evaluation of CLL patients.
authors.affiliation: Molecular Pathology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: valdorafrancesca@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Valdora
authors.affiliation: Molecular Pathology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: giovanna.cutrona@hsanmartino.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.affiliation: Molecular Pathology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: serena.matis@hsanmartino.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Matis
authors.affiliation: Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy; Biotechnology Research Unit, Aprigliano, A.O./ASP of Cosenza, Cosenza, Italy. Electronic address: fortunato_morabito@tiscali.it.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.affiliation: Molecular Pathology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: carlotta.massucco@libero.it.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Massucco
authors.affiliation: Animal Facility, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: laura.emionite@hsanmartino.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Emionite
authors.affiliation: Division of Histopathology and Cytopathology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: simona.boccardo@hsanmartino.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Boccardo
authors.affiliation: Department of Science of Health (DISSAL), University of Genoa, Via Antonio Pastore 1, 16132 Genoa, Italy. Electronic address: lukabasso89@gmail.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Basso
authors.affiliation: Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy; Biotechnology Research Unit, Aprigliano, A.O./ASP of Cosenza, Cosenza, Italy. Electronic address: annarecchia@tin.it.
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.affiliation: Division of Histopathology and Cytopathology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: sandra.salvi@hsanmartino.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Salvi
authors.affiliation: Department of Science of Health (DISSAL), University of Genoa, Via Antonio Pastore 1, 16132 Genoa, Italy. Electronic address: francescarosa892@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rosa
authors.affiliation: Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy; Biotechnology Research Unit, Aprigliano, A.O./ASP of Cosenza, Cosenza, Italy. Electronic address: massim.gentile@tiscali.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Diagnostic Imaging and Senology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: marco.ravina@hsanmartino.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Ravina
authors.affiliation: Diagnostic Imaging and Senology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: daniele.pace@hsanmartino.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pace
authors.affiliation: Diagnostic Imaging and Senology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: angela.castronovo@hsanmartino.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Castronovo
authors.affiliation: Animal Facility, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: michele.cilli@hsanmartino.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Cilli
authors.affiliation: Division of Histopathology and Cytopathology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: mauro.truini@ospedaleniguarda.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.affiliation: Diagnostic Imaging and Senology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: massimo.calabrese@hsanmartino.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Calabrese
authors.affiliation: Department of Oncology and Hemato-Oncology, University of Milano, Milan, Italy; Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: antonino.neri@unimi.it.
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.affiliation: Diagnostic Imaging and Senology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: carlo.neumaier@gmail.com.
authors.forename: Carlo Emanuele
authors.initials: CE
authors.lastname: Neumaier
authors.affiliation: Molecular Pathology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy; Department of Experimental Medicine, University of Genoa, Genoa, Italy. Electronic address: franco.fais@unige.it.
authors.forename: Franco
authors.initials: F
authors.lastname: Fais
authors.affiliation: Diagnostic Imaging and Senology, IRCCS - A.O.U. San Martino - IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Electronic address: gabriella.baio@abdn.ac.uk.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Baio
authors.affiliation: Scientific Direction, IRCCS - A.O.U. San Martino - IST, Genoa, Italy. Electronic address: manlio.ferrarini@hsanmartino.it.
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D004195:Disease Models, Animal; D005260:Female; D005290:Ferric Compounds; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D000069283:Rituximab; D013154:Spleen / Q000000981:diagnostic imaging* / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; C000499:ferric oxide; D000069283:Rituximab
keywords: Chronic lymphocytic leukemia (CLL); Disease monitoring; Magnetic resonance imaging (MRI); Ultra-small superparamagnetic iron oxide (USPIO); Xenograft NSG mice model