Levels and distribution of BCNU in GBM tumors following intratumoral injection of DTI-015 (BCNU-ethanol).

The alkylation products formed by in vitro treatment of DNA with tritium-labeled 1,3-bis(2-chloroethyl)-1-nitrosourea ((3)H-BCNU) were identified and quantified. Twelve adducts were resolved by high-performance liquid chromatography (HPLC). The principal DNA adducts formed by BCNU treatment corresponded to N-7-(2-hydroxyethyl)guanine (N7-HOEtG) (26%), N-7-(2-chloroethyl)guanine (15%), and phosphotriesters (19%).

Formation of DNA adducts and tumor growth delay following intratumoral administration of DTI-015.

Intratumoral (IT) administration of DTI-015 (BCNU in 100% ethanol) utilizes solvent facilitated perfusion for the treatment of tumors. RIF-1 tumors were treated by IT injection of either ethanol alone or 0.05-1.