Blue Earth Therapeutics Doses First Patient in Phase 1 Trial of Alpha-Emitting PSMA Radiopharmaceutical for mCRPC
核心洞察
Blue Earth Therapeutics (搜索) and UCL have dosed the first participant in a Phase 1 trial of Actinium (²²⁵Ac) rhPSMA-10.1 Injection for metastatic castrate-resistant prostate cancer (搜索).
The UCL-sponsored study will evaluate safety, tolerability, and radiation dosimetry in patients with PSMA (搜索)-positive mCRPC whose disease has progressed after prior therapy.
The alpha-emitting radiopharmaceutical delivers high-energy, short-range radiation to prostate cancer lesions, aiming for potent anti-tumour activity while limiting damage to healthy tissue.
Blue Earth Therapeutics (搜索), in collaboration with University College London (UCL), announced on July 9, 2026 that the first participant has been dosed in a Phase 1 clinical trial evaluating Actinium (²²⁵Ac) rhPSMA-10.1 Injection, an investigational alpha-emitting PSMA (搜索)-targeted radiopharmaceutical for metastatic castrate-resistant prostate cancer (搜索) (mCRPC). The study (NCT07414940), sponsored by UCL and conducted at UCL Hospital in London, marks the second clinical candidate to emerge from Blue Earth Therapeutics' oncology pipeline.
The trial is designed to assess safety, tolerability, and radiation dosimetry of the alpha-emitting agent in participants with PSMA (搜索)-positive mCRPC whose disease has progressed following prior therapy. Results are expected to characterise the side effect profile and inform dose selection for subsequent clinical research.
Mechanism and Rationale
Alpha-emitting radionuclides such as actinium-225 (²²⁵Ac) deliver a high amount of energy over a very short distance in tissue, causing irreparable DNA damage to targeted cancer cells while aiming to limit exposure to surrounding healthy tissue. When incorporated into a PSMA (搜索)-targeting molecule such as rhPSMA-10.1, this approach is designed to deliver localised radiation directly to prostate cancer lesions, potentially offering a targeted treatment strategy for patients with advanced disease.
The rhPSMA (radiohybrid Prostate-Specific Membrane Antigen) platform features four distinct molecular domains: a PSMA (搜索)-targeted receptor ligand, two labelling moieties that can be radiolabelled with diagnostic isotopes (¹⁸F or ⁶⁸Ga for PET imaging) or therapeutic isotopes (¹⁷⁷Lu or ²²⁵Ac for radioligand therapy), and a modifiable linker used to fine-tune pharmacokinetic characteristics. The technology originated at the Technical University of Munich, Germany, and Blue Earth Diagnostics acquired exclusive worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, with therapeutic rights secured in 2020 and subsequently sublicensed to sister company Blue Earth Therapeutics (搜索).
Pipeline Context
Actinium (²²⁵Ac) rhPSMA-10.1 Injection is the second clinical candidate in Blue Earth Therapeutics (搜索)' oncology pipeline, building on the company's ongoing Lutetium (¹⁷⁷Lu) rhPSMA-10.1 Injection clinical programme, which is currently in a Phase 2 trial. Together, these programmes reflect the company's work across both alpha- and beta-emitting radiopharmaceutical therapies.
"This study is an important step in advancing more precise treatment options for men with metastatic castrate-resistant prostate cancer (搜索)," said Professor Gert Attard, Director of the UCL Cancer Institute. "The combination of a highly targeted PSMA (搜索) approach with the potent, short-range effects of an alpha-emitting radionuclide offers a promising strategy to deliver meaningful anti-tumour activity while limiting toxicity. Early-phase trials such as this are essential for determining safety, refining dose and guiding how these therapies can be integrated into personalised treatment pathways to improve outcomes for patients."
Dr David Gauden, Chief Executive Officer of Blue Earth Therapeutics (搜索), added: "Initiation of this collaborative Phase 1 study represents an important milestone for Blue Earth Therapeutics and our investigational radiopharmaceutical therapy pipeline. Building on our clinical experience in both alpha- and beta-emitting radiopharmaceutical therapies, we are combining the targeting precision of rhPSMA with the alpha-emitting properties of actinium-225 to explore a potential treatment approach for patients with advanced prostate cancer."
Disease Burden and Unmet Need
Metastatic prostate cancer remains a significant clinical challenge. It has been forecast that in 2025 there would be 50,055 new cases of metastatic prostate cancer in the United States, encompassing both de novo diagnoses and recurrence from earlier stage diagnoses. Five-year survival for newly diagnosed metastatic prostate cancer stands at just 40.1%. While death rates from prostate cancer have declined over the past three decades, there remains considerable room to improve patient outcomes.
Neither Actinium (²²⁵Ac) rhPSMA-10.1 Injection nor Lutetium (¹⁷⁷Lu) rhPSMA-10.1 Injection has received marketing authorisation in any country or region. Blue Earth Therapeutics (搜索), incubated within the Bracco family of companies and bolstered by a Series A financing round in 2024 with additional investors, continues to advance its emerging pipeline focused initially on prostate cancer.