Evaluation of TK1 targeting carboranyl thymidine analogs as potential delivery agents for neutron capture therapy of brain tumors

Authors:   Rolf Barth,Weilian Yang,Robin Nakkula,Youngjoo Byun,Werner Tjarks,Lai Chu Wu,Peter Binns,Kent Riley,
Journal: Applied Radiation and Isotopes
https://doi.org/10.1016/j.apradiso.2015.06.031
Abstract: In this report we describe studies with N5-2OH, a carboranyl thymidine analog (CTA), which is a substrate for thymidine kinase 1 (TK1), using the F98 rat glioma model. In vivo BNCT studies have demonstrated that intracerebral (i.c.) osmotic pump infusion of N5-2OH yielded survival data equivalent to those obtained with i.v. administration of boronophenylalanine (BPA). The combination of N5-2OH and BPA resulted in a modest increase in MST of F98 glioma bearing rats compared to a statistically significant increase with the RG2 glioma model, as has been previously reported by us (Barth et al., 2008). This had lead us to synthesize a second generation of CTAs that have improved in vitro enzyme kinetics and in vivo tumor uptake (Agarwal et al., 2015).