Assessment of brain penetration and tumor accumulation of niraparib and olaparib: insights from multimodal imaging in preclinical models
Abstract
Abstract One of the most significant challenges in developing new treatments for primary and metastatic brain tumors is the requirement for crossing the blood-brain barrier (BBB). By examining the brain penetration and spatial distribution of drug candidates in animal models, we can gain valuable insights into their potential for clinical success. In this study, we used multimodal imaging alongside complementary analytical methods to assess the brain distribution of two clinically advanced poly(ADP-ribose) polymerase (PARP) inhibitors—niraparib and olaparib—across three preclinical models: healthy brain (nonhuman primates (NHPs)), primary brain tumors (mouse glioblastoma), and metastatic brain tumors (mouse breast cancer metastasis). The results suggest that niraparib has a superior ability (relative to olaparib) to penetrate the BBB, distribute widely throughout the brain, and accumulate in brain tumor lesions. These findings support further studies of niraparib as a potential treatment for tumors in the human brain.
Article Details
Authors (25)
M. Reid Groseclose
Jeremy A. Barry
Tina Skedzielewski
Yongle Pang
Yinghe Li
Gerald McDermott
Jennifer Deutsch
Chakravarthi Balabhadrapatruni
William Benson
David Lim
Hoang Tran
Elisabeth Minthorn
Casey Kmett
Theresa Roethke
Shannon Berry
Elaina McCormick
William Feeney
M. A. Ringenberg
Sean Maguire
Geeta Sharma
Amine Aziez
Elaine M. Paul
Kunal Taskar
Keyur Gada
Hasan Alsaid