title: Computed tomography imaging of transferrin targeting liposomes encapsulating both boron and iodine contrast agents by convection-enhanced delivery to F98 rat glioma for boron neutron capture therapy.
abstract: BACKGROUND
  To achieve potent tumor-selective antitumor efficacy by boron neutron capture therapy (BNCT), it is important to have a significant differential uptake of 10B between tumor cells and normal cells. This should enable BNCT to reduce damage to normal tissues compared with other radiation therapies.
  
  
  OBJECTIVE
  To augment the therapeutic efficacy of BNCT, we used transferrin-conjugated polyethylene glycol (PEG) (TF-PEG) liposome encapsulating sodium borocaptate and Iomeprol, an iodine contrast agent, with intratumoral convection-enhanced delivery (CED) in a rat glioma tumor model.
  
  
  METHODS
  The in vitro (10)B concentration of F98 rat glioma cells was determined by inductively coupled plasma atomic emission spectrometry after incubation with either TF-PEG or PEG liposomes. For in vivo biodistribution studies, (10)B concentrations within blood, normal brain tissue, and intracerebrally transplanted F98 cells were measured with inductively coupled plasma-atomic emission spectrometry after CED of the compounds, and computed tomography was performed at selected time intervals.
  
  
  RESULTS
  (10)B concentrations of F98 cultured glioma cells in vitro 6 hours after exposure to PEG and TF-PEG liposome were 16.1 and 51.9 ng (10)B/10(6) cells, respectively. (10)B concentrations in F98 glioma tissue 24 hours after CED were 22.5 and 82.2 μg/g, by PEG and TF-PEG liposome, respectively, with lower (10)B concentrations in blood and normal brain. Iomeprol provided vivid and stable enhanced computed tomography imaging of the transplanted tumor even 72 hours after CED by TF-PEG liposome. Conversely, tissue enhancement had already washed out at 24 hours after CED of the PEG liposomes.
  
  
  CONCLUSIONS
  The combination of TF-PEG liposome encapsulating sodium borocaptate and Iomeprol and intratumoral CED enables not only a precise and potent targeting of boron delivery to the tumor tissue, but also the ability to follow the trace of boron delivery administered intratumorally by real-time computed tomography.
authors.affiliation: Department of Neurosurgery, Osaka Medical College, Osaka, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Miyata
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawabata
authors.forename: Ryo
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Doi
authors.forename: Naokado
authors.initials: N
authors.lastname: Ikeda
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kuroiwa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kasaoka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Miyatake
mesh_terms: D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000532:radiotherapy*; D003287:Contrast Media / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000532:radiotherapy*; D007455:Iodine / Q000008:administration & dosage; D007479:Iopamidol / Q000008:administration & dosage / Q000031:analogs & derivatives; D008081:Liposomes; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed / Q000379:methods; D014168:Transferrin / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
chemical_list: D001894:Borohydrides; D003287:Contrast Media; D008081:Liposomes; D013438:Sulfhydryl Compounds; D014168:Transferrin; C014651:mercaptoundecahydrododecaborate; C057937:iomeprol; D007455:Iodine; D007479:Iopamidol