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Updated: Jun 1, 2026
A New Technique for Treating Low-risk Prostate Cancer—Super Active Surveillance
Published on: November 7, 2025
Developing imaging strategies for castration resistant prostate cancer
Josef J Fox1, Michael J Morris, Steven M Larson
1Nuclear Medicine Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. foxj@mskcc.org
Abstract:
Recent advances in the understanding of castrate-resistant prostate cancer (CRPC) have lead to a growing number of experimental therapies, many of which are directed against the androgen-receptor (AR) signaling axis. These advances generate the need for reliable molecular imaging biomarkers to non-invasively determine efficacy, and to better guide treatment selection of these promising AR-targeted drugs. Methods. We draw on our own experience, supplemented by review of the current literature, to discuss the systematic development of imaging biomarkers for use in the context of CRPC, with a focus on bone scintigraphy, F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) and PET imaging of the AR signaling axis. Results. The roadmap to biomarker development mandates rigorous standardization and analytic validation of an assay before it can be qualified successfully for use in an appropriate clinical context. The Prostate Cancer Working Group 2 (PCWG2) criteria for "radiographic" progression by bone scintigraphy serve as a paradigm of this process. Implemented by the Prostate Cancer Clinical Trials Consortium (PCCTC), these consensus criteria may ultimately enable the co-development of more potent and versatile molecular imaging biomarkers. Purported to be superior to single-photon bone scanning, the added value of Na(18)F-PET for imaging of bone metastases is still uncertain. FDG-PET already plays an integral role in the management of many diseases, but requires further evaluation before being qualified in the context of CRPC. PET tracers that probe the AR signaling axis, such as (18)F-FDHT and (89)Zr-591, are now under development as pharmacodynamic markers, and as markers of efficacy, in tandem with FDG-PET. Semi-automated analysis programs for facilitating PET interpretation may serve as a valuable tool to help navigate the biomarker roadmap. Conclusions. Molecular imaging strategies, particularly those that probe the AR signaling axis, have the potential to accelerate drug development in CRPC. The development and use of analytically valid imaging biomarkers will increase the likelihood of clinical qualification, and ultimately lead to improved patient outcomes.
Insights
Developing molecular imaging biomarkers is crucial for evaluating new therapies targeting androgen-receptor (AR) signaling in castrate-resistant prostate cancer (CRPC). These biomarkers help determine treatment efficacy and guide drug selection for improved patient outcomes.
Area of Science:
- Oncology
- Molecular Imaging
- Biomarker Development
Background:
- Castrate-resistant prostate cancer (CRPC) treatment is advancing with novel therapies targeting the androgen-receptor (AR) signaling axis.
- Reliable molecular imaging biomarkers are needed to assess treatment efficacy and guide drug selection for these therapies.
Purpose of the Study:
- To discuss the systematic development of molecular imaging biomarkers for CRPC.
- To focus on bone scintigraphy, F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET), and AR signaling axis PET imaging.
Main Methods:
- Review of current literature and expert experience in imaging biomarker development for CRPC.
- Discussion of established criteria (e.g., PCWG2) and emerging PET tracers for AR signaling axis evaluation.
Main Results:
- Rigorous standardization and analytic validation are essential for biomarker development and clinical qualification.
- While bone scintigraphy and FDG-PET have roles, their application in CRPC requires further evaluation. Novel PET tracers targeting the AR signaling axis are under development.
Conclusions:
- Molecular imaging, especially targeting the AR signaling axis, can accelerate CRPC drug development.
- Analytically valid imaging biomarkers are key to clinical qualification and improving patient outcomes in CRPC treatment.
