title: MRI-guided neutron capture therapy by use of a dual gadolinium/boron agent targeted at tumour cells through upregulated low-density lipoprotein transporters.
abstract: The upregulation of low-density lipoprotein (LDL) transporters in tumour cells has been exploited to deliver a sufficient amount of gadolinium/boron/ligand (Gd/B/L) probes for neutron capture therapy, a binary chemio-radiotherapy for cancer treatment. The Gd/B/L probe consists of a carborane unit (ten B atoms) bearing an aliphatic chain on one side (to bind LDL particles), and a Gd(III)/1,4,7,10-tetraazacyclododecane monoamide complex on the other (for detection by magnetic resonance imaging (MRI)). Up to 190 Gd/B/L probes were loaded per LDL particle. The uptake from tumour cells was initially assessed on cell cultures of human hepatoma (HepG2), murine melanoma (B16), and human glioblastoma (U87). The MRI assessment of the amount of Gd/B/L taken up by tumour cells was validated by inductively coupled plasma-mass-spectrometric measurements of the Gd and B content. Measurements were undertaken in vivo on mice bearing tumours in which B16 tumour cells were inoculated at the base of the neck. From the acquisition of magnetic resonance images, it was established that after 4-6 hours from the administration of the Gd/B/L-LDL particles (0.1 and 1 mmol kg(-1) of Gd and (10)B, respectively) the amount of boron taken up in the tumour region is above the threshold required for successful NCT treatment. After neutron irradiation, tumour growth was followed for 20 days by MRI. The group of treated mice showed markedly lower tumour growth with respect to the control group.
authors.affiliation: Department of Chemistry IFM and Molecular Imaging Center, Università di Torino, Via Nizza 52, 10125 Torino, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Geninatti-Crich
authors.forename: Diego
authors.initials: D
authors.lastname: Alberti
authors.forename: Ibolya
authors.initials: I
authors.lastname: Szabo
authors.forename: Annamaria
authors.initials: A
authors.lastname: Deagostino
authors.forename: Antonio
authors.initials: A
authors.lastname: Toppino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barge
authors.forename: Francesca
authors.initials: F
authors.lastname: Ballarini
authors.forename: Silva
authors.initials: S
authors.lastname: Bortolussi
authors.forename: Piero
authors.initials: P
authors.lastname: Bruschi
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Protti
authors.forename: Sabrina
authors.initials: S
authors.lastname: Stella
authors.forename: Saverio
authors.initials: S
authors.lastname: Altieri
authors.forename: Paolo
authors.initials: P
authors.lastname: Venturello
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D001895:Boron / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D005682:Gadolinium / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008546:Melanoma, Experimental; D051379:Mice; D015394:Molecular Structure; D017247:Neutron Capture Therapy / Q000379:methods*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D005682:Gadolinium; D001895:Boron