2015 Article ICNCT16 In-vivo Studies Radiobiology Small Boron compounds Year 2015

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

Applied Radiation and Isotopes, 2015

Authors:   Rolf Barth,Weilian Yang,Robin Nakkula,Youngjoo Byun,Werner Tjarks,Lai Chu Wu,Peter Binns,Kent Riley,
Journal: Applied Radiation and Isotopes
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).