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Updated: Jan 16, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Current and future perspectives on radioligand therapy in advanced prostate cancer
Buraq Ahmed1,2, Praful Ravi3
1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Abstract:
Radioligand therapy (RLT) has reshaped the treatment landscape of advanced prostate cancer (PCa), offering a precision medicine approach that integrates molecular imaging with targeted radionuclide delivery, in which radioactive isotopes are bound to molecules that aim to selectively target cancer cells. The approval of 177Lu-prostate-specific membrane antigen (PSMA)-617 for metastatic castration-resistant prostate cancer marked a major milestone, with randomized trials (VISION, PSMAfore) demonstrating significant improvements in overall and progression-free survival compared to standard therapies. Beyond beta-emitting agents, next-generation alpha emitters such as actinium-225 and beta/Auger electron-emitting isotopes like terbium‑161 are in active development, aiming to overcome resistance and target micrometastases with greater potency. Combination approaches, pairing RLT with poly(ADP-ribose) polymerase inhibitors, immune checkpoint blockade, or androgen receptor pathway inhibitors, for example, are under intense investigation, with early phase data indicating potential efficacy. Technical advances in imaging, personalized dosimetry, and molecular diagnostics may enable more precise patient selection and adaptive treatment strategies, such as dose adjustment based on dosimetry or target expression. Emerging RLT platforms target additional tumor markers, including human kallikrein 2 and six-transmembrane epithelial antigen of the prostate-2 as well as bispecific ligands, addressing disease heterogeneity and expanding therapeutic reach. Nonetheless, challenges remain around long-term hematologic and renal safety, radionuclide supply, protocol standardization, and global accessibility. Ongoing and future multicenter trials, collaborative consortia, and innovations in theranostics will be critical to defining optimal patient selection, sequencing with existing therapies, and embedding RLT as a key pillar in the management of advanced PCa.
Insights
Radioligand therapy (RLT) is revolutionizing advanced prostate cancer (PCa) treatment. This precision medicine approach uses targeted radioactive isotopes, showing improved survival and offering new combinations and targets for better outcomes.
Area of Science:
- Oncology
- Nuclear Medicine
- Precision Medicine
Background:
- Radioligand therapy (RLT) integrates molecular imaging and targeted radionuclide delivery for advanced prostate cancer (PCa).
- The approval of 177Lu-prostate-specific membrane antigen (PSMA)-617 signifies a major advancement, with trials showing improved survival.
- RLT offers a precision medicine approach by targeting cancer cells with radioactive isotopes.
Purpose of the Study:
- To review the current landscape and future directions of radioligand therapy in advanced prostate cancer.
- To highlight the efficacy of approved agents and the potential of emerging therapies.
- To discuss ongoing research, challenges, and the integration of RLT into standard care.
Main Methods:
- Review of clinical trials (e.g., VISION, PSMAfore) and ongoing research in RLT for advanced PCa.
- Analysis of next-generation radiotracers, including alpha emitters and beta/Auger electron emitters.
- Exploration of combination therapies and technical advances in imaging and dosimetry.
Main Results:
- 177Lu-PSMA-617 demonstrated significant improvements in overall and progression-free survival.
- Next-generation agents (e.g., actinium-225, terbium‑161) show promise for overcoming resistance and targeting micrometastases.
- Combination therapies and advanced diagnostics are under investigation for enhanced efficacy and patient selection.
Conclusions:
- RLT is a pivotal treatment for advanced PCa, with ongoing innovations expanding its therapeutic reach.
- Addressing challenges in safety, supply, standardization, and accessibility is crucial for wider adoption.
- Future multicenter trials and theranostic advancements will define RLT's optimal role in advanced PCa management.
