byWayne State University

Uptake and distribution of fluorescent ARi-FL probes in human prostate cancer cell line. Credit:Journal of Medicinal Chemistry(2025). DOI: 10.1021/acs.jmedchem.5c00836

Researchers at Wayne State University and the Barbara Ann Karmanos Cancer Institute have developed a chemical imaging probe that resists the breakdown of certain compounds in the body, giving doctors a more dependable way to track and potentially treat prostate cancer.

The research ispublishedin theJournal of Medicinal Chemistry.

WSU School of Medicine Assistant Professor of Oncology Sheryl Roberts, Ph.D., a member of the Karmanos Molecular Therapeutics Program, is the principal investigator on the study.

The National Cancer Institute listsprostate canceras the most common cancer and the second-leading cause of cancer death among men in the United States. The institute estimates prostate cancer will make up 15.4% of all new cancer cases in 2025.

"Certain hormone receptors in the body can drive cancer growth," Dr. Roberts said.

Her research focuses broadly on developing tools that either block or eliminate thesehormone receptors, including theandrogen receptor.

"Many patients develop resistance to current drugs. Being able to track AR (androgen receptor) over time could help doctors choose the right treatment sooner and more effectively," she said.

Despite three decades of progress, resistance inevitably develops, leading to the progression of castrate-resistant prostate cancer, a lethal stage of the disease. Evidence suggests that restoration of AR signaling, driven by genomic amplification of AR and subsequent overexpression, is a key driver of the progression, according to the study.

"We developed new probes, ARi-FL, that light up AR so it can be seen incancer cellsand tumors. It works robustly, stays stable and can detect AR even with mutations. This tool could help track AR in patients and guide better treatment choices," Dr. Roberts said.

She is now usingcomputational data, in collaboration with the College of Liberal Arts and Sciences Professor of Physics and Astronomy Christopher Kelly, Ph.D., to fine-tune the chemistry and advance toward radioligand strategies for next-generation probes.

More information: Saheed A. Ayodeji et al, High-Affinity Probes for Androgen Receptor Imaging: From Cells and In Silico Modeling to Whole-Body Fluorescent Applications, Journal of Medicinal Chemistry (2025). DOI: 10.1021/acs.jmedchem.5c00836 Journal information: Journal of Medicinal Chemistry

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