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Updated: Jan 29, 2026

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD
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Correlative Biomarker Analysis of PSMA Expression on CTCs and PSMA Imaging in a Phase I Study of PSMA-Targeted

Samir Zaidi1,2,3, Phillip H Kuo4, Tiago Paiva Prudente3

  • 1Department of Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 27, 2026
PubMed
Abstract

Insights

Biomarkers for prostate cancer therapy are crucial. This study found that assessing both PSMA imaging and circulating tumor cells (CTCs) reveals significant PSMA expression heterogeneity, impacting treatment response.

Area of Science:

  • Oncology
  • Molecular Imaging
  • Prostate Cancer Research

Background:

  • Prostate-specific membrane antigen (PSMA) targeted therapies offer clinical benefits in metastatic castration-resistant prostate cancer (mCRPC).
  • Limited response rates highlight the need for better biomarkers to understand PSMA expression heterogeneity.

Purpose of the Study:

  • To explore the relationship between PSMA imaging and PSMA expression on circulating tumor cells (CTCs).
  • To evaluate a PSMA-targeted small molecule and imaging agent in mCRPC patients.

Main Methods:

  • Phase 1 study of EC1169 (small molecule) and 99mTc-EC0652 (PSMA imaging agent) in 103 mCRPC patients.
  • Assessed PSMA-positive CTCs and their association with response and PSMA imaging via a CTC assay.
  • Utilized 99mTc-EC0652 SPECT imaging for lesion detection.

Main Results:

  • 99mTc-EC0652 SPECT imaging showed higher sensitivity for bone lesions than standard scans.
  • A decrease in PSMA-positive CTCs correlated with longer radiographic progression-free survival (rPFS) (8.0 vs. 2.9 months).
  • Patients with PSMA-positive imaging findings also had PSMA-negative CTCs, with some showing neuroendocrine prostate cancer (NEPC)-like morphology.

Conclusions:

  • EC1169 demonstrated limited activity.
  • Significant heterogeneity in PSMA expression on CTCs was observed, even in patients with PSMA-positive imaging.
  • Combined assessment of PSMA-based CTCs and imaging is important for future mCRPC trials.

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