title: Manganese-enhanced MRI reveals early-phase radiation-induced cell alterations in vivo.
abstract: For tumor radiotherapy, the in vivo detection of early cellular responses is important for predicting therapeutic efficacy. Mn(2+) is used as a positive contrast agent in manganese-enhanced MRI (MEMRI) and is expected to behave as a mimic of Ca(2+) in many biologic systems. We conducted in vitro and in vivo MRI experiments with Mn(2+) to investigate whether MEMRI can be used to detect cell alterations as an early-phase tumor response after radiotherapy. Colon-26 cells or a subcutaneously grafted colon-26 tumor model were irradiated with 20 Gy of X-rays. One day after irradiation, a significant augmentation of G2-M-phase cells, indicating a cell-cycle arrest, was observed in the irradiated cells in comparison with the control cells, although both early and late apoptotic alterations were rarely observed. The MEMRI signal in radiation-exposed tumor cells (R1: 0.77 ± 0.01 s(-1)) was significantly lower than that in control cells (R1: 0.82 ± 0.01 s(-1)) in vitro. MEMRI signal reduction was also observed in the in vivo tumor model 24 hours after irradiation (R1 of radiation: 0.97 ± 0.02 s(-1), control: 1.10 ± 0.02 s(-1)), along with cell-cycle and proliferation alterations identified with immunostaining (cyclin D1 and Ki-67). Therefore, MEMRI after tumor radiotherapy was successfully used to detect cell alterations as an early-phase cellular response in vitro and in vivo.
authors.affiliation: Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Saito
authors.forename: Sumitaka
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Aiko
authors.initials: A
authors.lastname: Sekita
authors.forename: Rumiana
authors.initials: R
authors.lastname: Bakalova
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.forename: Kenya
authors.initials: K
authors.lastname: Murase
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D045744:Cell Line, Tumor; D002712:Chlorides; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000532:radiotherapy*; D003287:Contrast Media; D004195:Disease Models, Animal; D005434:Flow Cytometry; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D019786:Gadolinium DTPA; C025340:manganese chloride