Assessment of brain penetration and tumor accumulation of niraparib and olaparib: insights from multimodal imaging in preclinical models
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.
Authors
- Theresa J. Roethke
- William E. Feeney (ORCID: https://orcid.org/0000-0002-7475-4724)
- Hoang Tran (ORCID: https://orcid.org/0000-0003-1529-5692)
- William H. Benson
- Casey Kmett
- Yongle Pang
- Elaina McCormick
- Jeremy A. Barry (ORCID: https://orcid.org/0000-0003-4096-8924)
- Jennifer Deutsch
- Elisabeth A. Minthorn
- Elaine Paul (ORCID: https://orcid.org/0000-0002-2975-2316)
- M. Reid Groseclose (ORCID: https://orcid.org/0000-0002-9783-4057)
- Shannon Berry
- Dae‐Sik Lim (ORCID: https://orcid.org/0000-0003-2356-7555)
- Yinghe Li (ORCID: https://orcid.org/0000-0002-3838-237X)
- Tina Skedzielewski
- Amine Aziez
- Gerald R. McDermott
- Kunal S. Taskar (ORCID: https://orcid.org/0000-0001-9979-8267)
- Hasan Alsaid (ORCID: https://orcid.org/0000-0001-6600-2146)
- Sean Maguire (ORCID: https://orcid.org/0000-0002-4620-1161)
- Keyur Gada
- Michael A. Ringenberg (ORCID: https://orcid.org/0000-0001-9504-5225)
- Geeta Sharma
- Chakravarthi Balabhadrapatruni
Institutions
- Institute of Molecular Bioimaging and Physiology (IT)
- Cancer Research And Biostatistics (US)
- GlaxoSmithKline (United States) (US)
- Glaxosmithkline (Finland) (FI)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1038/s41598-025-18255-9
- Citations
- 1
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 1.05