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

Appl Radiat Isot. 2015 Dec:106:251-5. doi: 10.1016/j.apradiso.2015.06.031. Epub 2015 Jul 2.

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).

Keywords: BNCT; Carboranyl thymidine analogs; F98 rat glioma; N5-2OH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Boron Neutron Capture Therapy*
  • Brain Neoplasms / radiotherapy*
  • Rats
  • Thymidine / administration & dosage*
  • Thymidine / analogs & derivatives
  • Thymidine Kinase / drug effects*

Substances

  • Thymidine Kinase
  • thymidine kinase 1
  • Thymidine