title: In vivo imaging of cell proliferation for a dynamic, whole body, analysis of undesired drug effects.
abstract: Noninvasive in vivo imaging offers a novel approach to preclinical studies opening the possibility of investigating biological events in the spatiotemporal dimension (eg, in any district of the body in time). Toxicological analysis may benefit from this novel approach through precise identification of the time and the target organs of toxicity manifestations, and assessment of the reversibility of toxic insults. The current limitation for routine application of this technology is the lack of appropriate surrogate markers for imaging toxicological events. Here, we demonstrate that in vivo imaging of a proliferation marker is capable of measuring the reduction of cell proliferation due to genotoxic/apoptotic agents, γ rays or antineoplastic drugs, or the increased proliferation associated with the inflammatory and regenerative reactions occurring after a toxic insult. A number of tools are currently available for imaging proliferation in preclinical and clinical settings, however our data provide a novel way to translate the evidence of toxic effects obtained in preclinical animal studies, by the direct, noninvasive measure of dividing cells in humans.
authors.affiliation: *Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy; Experimental Oncology Department, Istituto Regina Elena, 00158 Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Rizzi
authors.affiliation: *Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy; Experimental Oncology Department, Istituto Regina Elena, 00158 Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Manni
authors.affiliation: *Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy; Experimental Oncology Department, Istituto Regina Elena, 00158 Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vantaggiato
authors.affiliation: *Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy; Experimental Oncology Department, Istituto Regina Elena, 00158 Rome, Italy.
authors.forename: Giacomo Andrea
authors.initials: GA
authors.lastname: Delledonne
authors.affiliation: *Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy; Experimental Oncology Department, Istituto Regina Elena, 00158 Rome, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Gentileschi
authors.affiliation: *Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy; Experimental Oncology Department, Istituto Regina Elena, 00158 Rome, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
authors.affiliation: *Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy; Experimental Oncology Department, Istituto Regina Elena, 00158 Rome, Italy paolo.ciana@unimi.it piaggio@ifo.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Piaggio
authors.affiliation: *Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy; Experimental Oncology Department, Istituto Regina Elena, 00158 Rome, Italy paolo.ciana@unimi.it piaggio@ifo.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciana
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D000069286:Bortezomib / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects*; D000077143:Docetaxel; D017930:Genes, Reporter; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008822:Mice, Transgenic; D061848:Optical Imaging; D012038:Regeneration / Q000187:drug effects* / Q000528:radiation effects*; D043823:Taxoids / Q000494:pharmacology; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D015127:9,10-Dimethyl-1,2-benzanthracene; D000069286:Bortezomib; D049409:Luciferases, Firefly
keywords: antineoplastic toxicology; cell proliferation; in vivo imaging; kinetics of toxic effects; toxicological markers