Towards improved boron neutron capture therapy agents: evaluation of in vitro cellular uptake of a glutamine-functionalized carborane.
Sodium borocaptate (BSH) is widely used for boron neutron capture therapy (BNCT) of brain tumors. One drawback is the large uptake by the liver causing a decrease of its availability at the tumor region as well as bringing about toxicity problems. A novel carborane-based compound containing a boron payload very similar to that of BSH has been synthesized and tested on rat glioma (C6) cells, hepatoma tissue culture (HTC) cells, and hepatocytes. The newly synthesized system consists of an o-carborane unit (C(2)B(10)H(11), o-CB) conjugated to a glutamine residue through a proper spacer, namely, o-CB-Gln. As compared with BSH, it showed the same uptake by C6 cells, but a 50% decrease in uptake by HTC cells and an 80% decrease in uptake by healthy hepatocytes. On this basis o-CB-Gln appears an interesting candidate for BNCT of brain tumors as it is expected to have a therapeutic index analogous to that of BSH accompanied by a much lower liver toxicity.
Department of Chemistry IFM, University of Turin, Turin, Italy.
Antonella
A
Crivello
Carlo
C
Nervi
Roberto
R
Gobetto
Simonetta Geninatti
SG
Crich
Iboya
I
Szabo
Alessandro
A
Barge
Antonio
A
Toppino
Annamaria
A
Deagostino
Paolo
P
Venturello
Silvio
S
Aime
D000818:Animals; D001692:Biological Transport; D001894:Borohydrides / Q000627:therapeutic use; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy; D002417:Cattle; D045744:Cell Line, Tumor; D005973:Glutamine / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000627:therapeutic use
D001894:Borohydrides; D001896:Boron Compounds; D013438:Sulfhydryl Compounds; D005973:Glutamine; C014651:mercaptoundecahydrododecaborate