BNCT (Boron Neutron Capture Therapy) is a binary therapy for the treatment of cancer based on the selective uptake of the stable 10B isotope by tumor cells, followed by irradiation with low energy thermal neutrons. In order to be effective BNCT requires 15–30 μg of 10B per g of tumor, therefore, in vivo visualization of 10B distribution is important.1 Thanks to its superb spatial resolution MRI appears to be one of the most appropriate technique to tackle this task. In this work the synthesis and the in vitro and in vivo biological evaluation of a panel of new dual agents for MRI/BNCT applications is reported. Those agents are obtained starting form a versitile dicarbaclosododecaborane intermediate, which assures a high payload of 10B atoms and can be functionalized with different biological vectors and different MRI probes. On one side the carborane cage has been functionalized with lipophilic moieties, like palmityl chains2,3 (AT101) or double-tailed moiety (AT102) or colesterol (AT103) in order to bind the carborane cage to the nanosized vector represented by LDL or liposomes (the real biological vectors). On the other side the carborane has been funtionalized with a Gd-DOTA complex, which allow the boron concentration in cell by means of MRI detection to be quantified.

Synthesis and biological evaluation of new dual agentsfor MRI/BNCT applications

TOPPINO, Antonio;DEAGOSTINO, Annamaria;GENINATTI CRICH, Simonetta;ALBERTI, DIEGO;VENTURELLO, Paolo;AIME, Silvio
2012-01-01

Abstract

BNCT (Boron Neutron Capture Therapy) is a binary therapy for the treatment of cancer based on the selective uptake of the stable 10B isotope by tumor cells, followed by irradiation with low energy thermal neutrons. In order to be effective BNCT requires 15–30 μg of 10B per g of tumor, therefore, in vivo visualization of 10B distribution is important.1 Thanks to its superb spatial resolution MRI appears to be one of the most appropriate technique to tackle this task. In this work the synthesis and the in vitro and in vivo biological evaluation of a panel of new dual agents for MRI/BNCT applications is reported. Those agents are obtained starting form a versitile dicarbaclosododecaborane intermediate, which assures a high payload of 10B atoms and can be functionalized with different biological vectors and different MRI probes. On one side the carborane cage has been functionalized with lipophilic moieties, like palmityl chains2,3 (AT101) or double-tailed moiety (AT102) or colesterol (AT103) in order to bind the carborane cage to the nanosized vector represented by LDL or liposomes (the real biological vectors). On the other side the carborane has been funtionalized with a Gd-DOTA complex, which allow the boron concentration in cell by means of MRI detection to be quantified.
XXXIV CONVEGNO NAZIONALE DIVISIONE DI CHIMICA ORGANICA
Pavia
10-14/09/2012
Atti del Convegno
Società Chimica Italiana
148
148
Antonio Toppino; Annamaria Deagostino; Simonetta Geninatti; Diego Alberti; Paolo Venturello; Silvio Aime
File in questo prodotto:
File Dimensione Formato  
Pavia2012congresso chimica organicapagina148.pdf

Accesso riservato

Tipo di file: MATERIALE NON BIBLIOGRAFICO
Dimensione 124.2 kB
Formato Adobe PDF
124.2 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/120651
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 21
  • ???jsp.display-item.citation.isi??? ND
social impact