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Updated: Feb 11, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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First-in-human evaluation of [211At]YF2 in patients with metastatic castration-resistant prostate cancer

Xiaoai Wu1, Yongzhao Xiang1, Michael R Zalutsky2

  • 1Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China.

European Journal of Nuclear Medicine and Molecular Imaging
|February 10, 2026
PubMed
Abstract

Insights

The novel alpha-particle therapy agent [211At]YF2 was safely administered to metastatic castration-resistant prostate cancer patients. This study confirmed clear delineation of metastatic lesions and favorable dosimetry, supporting further clinical development of [211At]YF2.

Area of Science:

  • Nuclear Medicine and Radiopharmaceutical Therapy
  • Oncology and Prostate Cancer Research
  • Medical Imaging and Dosimetry

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) remains a significant clinical challenge.
  • Prostate-specific membrane antigen (PSMA) is a validated target for mCRPC imaging and therapy.
  • Alpha-particle emitters offer potent therapeutic potential due to their high linear energy transfer.

Purpose of the Study:

  • To evaluate the safety, biodistribution, and dosimetry of the alpha-particle emitting PSMA inhibitor [211At]YF2 in a Phase 0 microdose study.
  • To assess the feasibility of using X-rays from 211At decay for imaging metastatic lesions in mCRPC patients.

Main Methods:

  • Initial biodistribution studies were conducted in CD-1 mice.
  • Three mCRPC patients with PSMA-positive metastases received intravenous [211At]YF2 (29.6-44.4 MBq).
  • Whole-body planar imaging and SPECT/CT scans were performed at various time points; safety and dosimetry were assessed using Rapid 3D-RD software.

Main Results:

  • [211At]YF2 was well-tolerated in patients, with all adverse events being Grade 2 or lower.
  • High initial uptake was observed in kidneys, bladder, salivary glands, and thyroid, followed by rapid clearance.
  • Metastatic lesions were clearly visualized, with dosimetry indicating a dose of 31.4 mGy/MBq to the most prominent metastasis and a kidney dose of 15.3 mGy/MBq.

Conclusions:

  • [211At]YF2 can be safely administered to mCRPC patients, enabling clear delineation of metastatic lesions.
  • The observed biodistribution and dosimetry profile of [211At]YF2 are favorable for clinical application.
  • These findings support the further clinical development of [211At]YF2 for mCRPC treatment.
Keywords:
Astatine-211Prostate-specific membrane antigenTargeted α-therapy[211At]YF2

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