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Updated: Jan 12, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Effective treatment of human prostate carcinoma xenografts with Single-Dose PSMA-targeted [211At]YF2
Yutian Feng1, Truc T Huynh1, Yongxiang Zheng1
1Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA.
Purpose:
[211At]YF2 exhibits high cytotoxicity in vitro and prolonged retention in prostate-specific membrane antigen (PSMA) expressing xenografts. Herein we evaluated its therapeutic efficacy in athymic mice with PSMA + PC3 xenografts.
Methods:
The antitumor efficacy of single-dose [211At]YF2 prepared with HPLC purification and no iodo YF2 carrier (Experiment 1) and without HPLC purification with iodo YF2 carrier (Experiments 2 and 3) was evaluated: Experiment (1) groups of mice (n = 10) received PBS as control, 1.5 MBq, and 2.2 MBq [211At]YF2; Experiment (2) groups of mice (n = 10) received PBS, 2, 3, 5, or 8 MBq of [211At]YF2; and Experiment (3) groups of mice (n = 5) received PBS, 9 MBq or 12 MBq [211At]YF2. After treatment, mice were monitored for tumor growth and body weight, and the maximum tolerated dose (MTD) was determined.
Results:
Co-administration of iodinated YF2 resulted in a 5-fold increase in tumor-to-kidney dose ratio for [211At]YF2. Significant tumor growth inhibition (TGI) and survival benefit were seen for mice treated with [211At]YF2, and a single dose of 2.2 MBq led to a 3.6-fold increase in median survival. In second study, a dose-dependent TGI and survival benefit was observed for the treatment groups, with 8 MBq of [211At]YF2 inducing a 4.5-fold increase in median survival. Radiation toxicity was seen in mice treated with 9 or 12 MBq [211At]YF2, indicating an MTD of 8 MBq.
Conclusion:
Single dose of [211At]YF2 showed significant antitumor efficacy and survival benefit at all doses with several long-term survivors, and a single dose of 8 MBq [211At]YF2 was well tolerated.
Insights
Astatine-211 labeled YF2 ([211At]YF2) demonstrated significant prostate cancer tumor growth inhibition and survival benefits in mice. The maximum tolerated dose was determined to be 8 MBq, showing therapeutic potential.
Area of Science:
- Nuclear Medicine
- Radiopharmaceutical Therapy
- Oncology
Background:
- Prostate-specific membrane antigen (PSMA) is a validated target for prostate cancer therapy.
- [211At]YF2 exhibits high in vitro cytotoxicity and prolonged retention in PSMA-expressing tumors.
- Evaluating the therapeutic efficacy of [211At]YF2 in vivo is crucial for its clinical translation.
Purpose of the Study:
- To assess the therapeutic efficacy of [211At]YF2 in an athymic mouse model with PSMA-positive PC3 xenografts.
- To determine the maximum tolerated dose (MTD) of [211At]YF2.
- To evaluate the impact of iodinated YF2 carrier on the tumor-to-kidney dose ratio.
Main Methods:
- Three experiments were conducted to evaluate the antitumor efficacy of single-dose [211At]YF2.
- Doses ranged from 1.5 MBq to 12 MBq, with varying preparation methods (HPLC purification vs. no purification, with/without carrier).
- Tumor growth, body weight, and survival were monitored; MTD was determined based on observed toxicities.
Main Results:
- [211At]YF2 demonstrated significant tumor growth inhibition (TGI) and survival benefit across tested doses.
- A single dose of 2.2 MBq increased median survival by 3.6-fold, while 8 MBq increased it by 4.5-fold.
- Co-administration of iodinated YF2 improved the tumor-to-kidney dose ratio; the MTD was established at 8 MBq due to observed radiation toxicity at higher doses.
Conclusions:
- Single-dose [211At]YF2 exhibits significant antitumor efficacy and provides a survival benefit in PSMA-positive xenografts.
- Several long-term survivors were observed, indicating durable therapeutic effects.
- A single dose of 8 MBq [211At]YF2 was well-tolerated and represents a potential therapeutic dose.
