title: MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment.
abstract: The purpose of the work was to set-up a simple method to evaluate the contribution of Mn(2+) ions in the intra- and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by "silencing" the relaxation enhancement arising from Mn(2+) ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10-tetraazacyclododecane-1,7-diacetic acid) towards Mn(2+) ions, as the addition of Ca-DO2A to a solution of MnCl2 causes a drop of relaxivity upon the formation of the highly stable and low-relaxivity Mn-DO2A. It has been proved that the sequestering ability of DO2A towards Mn(2+) ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn-DO2A does not enter cell membranes, nor does the presence of Ca-DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T1 -weighted images is taken as evidence of the sequestration of extracellular Mn(2+) ions upon addition of Ca-DO2A. By applying the method to B16F10 tumor bearing mice, T1 decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP-MS measurements.
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences & Molecular Imaging Center, University of Torino, Torino, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Gianolio
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences & Molecular Imaging Center, University of Torino, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Arena
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences & Molecular Imaging Center, University of Torino, Torino, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Di Gregorio
authors.affiliation: Department of Chemistry, University of Milano, Milano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pagliarin
authors.affiliation: Department of Chemistry, University of Milano, Milano, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Delbianco
authors.affiliation: Diagnostic Imaging and Senology Unit, National Cancer Institute - IST, Azienda Ospedaliera Universitaria San Martino - IRCCS, Genova, Italy.|Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, UK.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Baio
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences & Molecular Imaging Center, University of Torino, Torino, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C561329:1,4,7,10-tetraazacyclododecane-1,7-diacetic acid; D006573:Heterocyclic Compounds, 1-Ring; D008345:Manganese
keywords: DO2A; MEMRI; calcium receptors; cellular and molecular cancer imaging; molecular and cellular probes; relaxivity