Evaluation of TK1 targeting carboranyl thymidine analogs as potential delivery agents for neutron capture therapy of brain tumors.
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).
The Ohio State University, Department of Pathology, Columbus, OH 43210, USA. Electronic address: rolf.barth@osumc.edu.
Rolf F
RF
Barth
The Ohio State University, Department of Pathology, Columbus, OH 43210, USA.
Weilian
W
Yang
The Ohio State University, Department of Pathology, Columbus, OH 43210, USA.
Robin J
RJ
Nakkula
The Ohio State University, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Columbus, OH 43210, USA.
Youngjoo
Y
Byun
The Ohio State University, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Columbus, OH 43210, USA.
Werner
W
Tjarks
The Ohio State University, Department of Molecular and Cellular Biochemistry and Department of Internal Medicine, Columbus, OH 43210, USA.
Lai Chu
LC
Wu
Mount Auburn Hospital, Department of Radiology, Cambridge, MA 02138, USA.
Peter J
PJ
Binns
Massachusetts General Hospital, Department of Radiation Oncology, Boston, MA 02114, USA.
Kent J
KJ
Riley
D000818:Animals; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000532:radiotherapy*; D051381:Rats; D013936:Thymidine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D013937:Thymidine Kinase / Q000187:drug effects*
D013937:Thymidine Kinase; C092717:thymidine kinase 1; D013936:Thymidine
BNCT; Carboranyl thymidine analogs; F98 rat glioma; N5-2OH