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.
Crivello
Antonella
A
Department of Chemistry IFM, University of Turin, Turin, Italy.
Nervi
Carlo
C
Gobetto
Roberto
R
Crich
Simonetta Geninatti
SG
Szabo
Iboya
I
Barge
Alessandro
A
Toppino
Antonio
A
Deagostino
Annamaria
A
Venturello
Paolo
P
Aime
Silvio
S
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