Synthesis of a carborane-containing cholesterol derivative and evaluation as a potential dual agent for MRI/BNCT applications

Abstract

Abstract.In this study the synthesis and characterization of a new dual, imaging and therapeutic, agent is proposed with the aim of improving the efficacy of Boron Neutron Capture Therapy (BNCT) in cancer treatment. The agent (Gd-B-AC01) consists of a carborane unit (ten boron atoms) bearing a cholesterol unit on one side (to pursue the incorporation into the liposome bi-layer), and a Gd(III)/1,4,7,10-tetraazacyclododecane monoamide complex on the other side (as MRI reporter to attain the quantification of B/Gd concentration). In order to endow the BNCT agent with specific delivery properties, the liposome embedded with the MRI/BNCT dual probes has been functionalized with a peghilated phospholipid containing a folic acid residue at the end of the PEG

Synthesis, relaxation properties and in vivo assessment of a carborane-GdDOTA-monoamide conjugate as an MRI blood pool contrast agent

“…Propargylamine (3.0 g, 54.5 mmol) was dissolved in 100 mL of dichloromethane (DCM) and 100 mL of saturated aqueous sodium bicarbonate (NaHCO 3 ) were added. HRMS (m/z): Calcd for C 19 The reaction mixture was slowly allowed to warm to room temperature (RT).…”

“…15 However, later it was found that this compound was not suitable for BNCT due to poor tumor accumulation. [17][18][19] Results and discussion Synthesis of CB-GdDOTA-MA Our efforts to prepare CB-GdDOTA-MA started with the synthesis of alkyne 1 in 89% yield by reacting propargylamine with bromoacetyl bromide. Such lipophilic conjugates are designed to form nanoparticles (micelles or liposomes) and deliver sufficient boron atoms to the tumor via the enhanced permeability and retention (EPR) effect.…”

Synthesis, characterization and radiolabeling of carborane-functionalized tetrazines for use in inverse electron demand Diels–Alder ligation reactions

“…Dicarba-closo-dodecaboranes are attractive synthons for developing inorganic pharmaceuticals [1][2][3][4][5][6][7][8], radiopharmaceuticals [9], fluorophores [10], and boron neutron capture therapy (BNCT) [11][12][13][14][15] or synovectomy (BNCS) agents [16,17]. Carboranes are biocompatible, resistant to enzymatic modification, and can be linked to or incorporated within a variety of different targeting vectors.…”

An amphiphilic block copolymer conjugated with carborane and a NIR fluorescent probe for potential imaging-guided BNCT therapy

“…The LET range is limited to a diameter of 5-9 μm which is in accord with the size of a single cell. [11][12][13][14] However, carborane compounds are generally hydrophobic substances which cannot be dispersed in aqueous solution. A higher total dose can be received than that of the adjacent normal tissues resulting from a greater concentration of 10 B in tumor cells.…”