Boron neutron capture therapy (BNCT) is a binary strategy for cancer treatment based on nuclear 10B interaction with a thermal neutron flow. This therapy requires the introduction within cancer cells of 15-30 µg B per gr of tu-mor tissue with high selectivity. These boron amounts are necessary for an efficient treatment, while a selective introduction in tumor preserves other cells from damages. Another aspect is the importance of following in vivo 10B distribution to check the tumor position. In order to reach these aims, several BNCT agents have been functiona-lized with different biological vectors (to improve their selective absorption in tumour cells) and with different MRI probes (to follow the in vivo boron distribution). In this work a new sinthetic strategy for dicarba-closo-dodecaboranes (RR’C2B10H10) is reported. Starting from decaborane (B10H14), these molecules show good in vivo stability and powerful versatility, allowing the boron cage with different biological vectors and MRI probes to be functionalized. Hydroboration reaction is the main synthetic step to functionalize decaborane with terminal alkenes, achieving 6-alkyldecaboranes (6-R-B10H13). Starting from these B-substituted alkyldecaboranes, dehydrogenative insertion reaction with terminal alkynes allows dicarba-closo-dodecaboranes to be synthetized. On one side the carborane cage has been functionalized with a lipophilic moiety, in order to allow the interaction with LDLs or liposomes (the real biological vectors). On the other side the carborane cage has been functionalized by dehydrogenative insertion reaction with a terminal alkyne subsequently joined with a Gd-DOTA complex as MRI probe.
New Synthetic Strategy of MRI/BNCT Agents Based on Hydroboration Reaction
BOGGIO, PAOLO;TOPPINO, Antonio;GENINATTI CRICH, Simonetta;ALBERTI, DIEGO;AIME, Silvio;DEAGOSTINO, Annamaria
2014-01-01
Abstract
Boron neutron capture therapy (BNCT) is a binary strategy for cancer treatment based on nuclear 10B interaction with a thermal neutron flow. This therapy requires the introduction within cancer cells of 15-30 µg B per gr of tu-mor tissue with high selectivity. These boron amounts are necessary for an efficient treatment, while a selective introduction in tumor preserves other cells from damages. Another aspect is the importance of following in vivo 10B distribution to check the tumor position. In order to reach these aims, several BNCT agents have been functiona-lized with different biological vectors (to improve their selective absorption in tumour cells) and with different MRI probes (to follow the in vivo boron distribution). In this work a new sinthetic strategy for dicarba-closo-dodecaboranes (RR’C2B10H10) is reported. Starting from decaborane (B10H14), these molecules show good in vivo stability and powerful versatility, allowing the boron cage with different biological vectors and MRI probes to be functionalized. Hydroboration reaction is the main synthetic step to functionalize decaborane with terminal alkenes, achieving 6-alkyldecaboranes (6-R-B10H13). Starting from these B-substituted alkyldecaboranes, dehydrogenative insertion reaction with terminal alkynes allows dicarba-closo-dodecaboranes to be synthetized. On one side the carborane cage has been functionalized with a lipophilic moiety, in order to allow the interaction with LDLs or liposomes (the real biological vectors). On the other side the carborane cage has been functionalized by dehydrogenative insertion reaction with a terminal alkyne subsequently joined with a Gd-DOTA complex as MRI probe.
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