Atrasentan (ABT-627) enhances perfusion and reduces hypoxia in a human tumor xenograft model.
The endothelin-1 antagonist, Atrasentan (ABT-627) was used to modify perfusion in the human tumor xenograft model, HT29, growing in nude mice. Atrasentan produced a significant increase in perfusion, as measured in vivo by Gd-DTPA DCE-MRI. Changes in tumor hypoxia were assessed by comparing the binding of two hypoxia tracers, pimonidazole and EF5 given before and after Atrasentan administration. In vehicle-treated controls, the distribution of EF5 and pimonidazole was very similar. However, Atrasentan treatment was associated with decreased uptake of the second hypoxia tracer (EF5), relative to the first (pimonidazole). Although Atrasentan had no independent effect on the growth of HT29 tumors, Atrasentan combined with 20 Gy radiation led to a modest but significant increase in tumor growth delay compared to radiation alone.
Yang
Kwang Mo
KM
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Russell
James
J
Lupu
Mihaela E
ME
Cho
Hyungjoon
H
Li
Xiao-Feng
XF
Koutcher
Jason A
JA
Ling
C Clifton
CC
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000077868:Atrasentan; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D017341:Etanidazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D019786:Gadolinium DTPA; D019073:HT29 Cells; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics; D000860:Hypoxia; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D010477:Perfusion; D011759:Pyrrolidines / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics; D011878:Radiotherapy / Q000379:methods; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D005466:Fluorocarbons
D000077868:Atrasentan; D017341:Etanidazole; D019786:Gadolinium DTPA; D006845:Hydrocarbons, Fluorinated; D009593:Nitroimidazoles; D011759:Pyrrolidines; D011838:Radiation-Sensitizing Agents; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons; C033815:pimonidazole