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Updated: Nov 21, 2025
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Pre-clinical Orthotopic Murine Model of Human Prostate Cancer
Published on: August 29, 2016
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PSA-Targeted Alpha-, Beta-, and Positron-Emitting Immunotheranostics in Murine Prostate Cancer Models and Nonhuman
Darren R Veach1,2, Claire M Storey3, Katharina Lückerath3,4,5,6
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
Summary
This study shows hu5A10, a novel antibody targeting prostate-specific antigen (PSA), effectively treats prostate cancer in preclinical models. Radiolabeled hu5A10 demonstrates theranostic potential for advanced prostate cancer therapy.
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Immunotherapy
Background:
- Androgen receptor (AR) signaling inhibitors are standard prostate cancer treatments.
- Therapeutic resistance to AR inhibitors is common due to AR functionality restoration.
- Novel therapeutic strategies targeting AR are critically needed.
Purpose of the Study:
- To investigate the theranostic potential of hu5A10, a humanized monoclonal antibody targeting free prostate-specific antigen (PSA, KLK3).
- To evaluate the efficacy and biodistribution of radiolabeled hu5A10 in preclinical prostate cancer models.
Main Methods:
- Radiolabeling hu5A10 with isotopes (89Zr, 90Y, 225Ac) for imaging and therapy.
- In vivo studies using LNCaP-AR xenografts and KLK3_Hi-Myc transgenic mice.
- Assessment of biodistribution, tumor uptake, therapeutic efficacy, and pharmacokinetics in mice and nonhuman primates (NHPs).
Main Results:
- Radiolabeled hu5A10 showed specific tumor uptake correlating with PSA expression.
- Treatment with 90Y- or 225Ac-labeled hu5A10 significantly reduced tumor burden and prolonged survival.
- Complete responses were observed in a subset of animals treated with 225Ac-hu5A10.
- 89Zr-hu5A10 PET visualized prostate in NHPs, consistent with mouse pharmacokinetics.
Conclusions:
- Hu5A10 establishes a new theranostic agent for highly specific and effective targeting of AR in PSA-expressing tissues.
- Preclinical data support the clinical translation of radiolabeled hu5A10 for prostate cancer treatment.
- This approach offers a promising strategy for overcoming therapeutic resistance in prostate cancer.
