Imaging Cell Surface Plectin in PDAC Patients - A First-In-Human Phase 0 Study Report

Julien Dimastromatteo ¹, Jiang He ^2,3, Reid B Adams ⁴

⁰Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. ju.dimastro@gmail.com.

Molecular Imaging and Biology +

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March 27, 2025

View abstract on PubMed

Summary

This study shows PTP-01 can target cancer-specific plectin (CSP) in pancreatic tumors. CSP is a promising target for new cancer therapies.

Area Of Science

Oncology
Molecular Biology
Radiochemistry

Background

Plectin is an intracellular protein crucial for cell structure.
Cancer-specific plectin (CSP) is found on the surface of various cancer cells, influencing tumor progression.
CSP-positive tumors, including pancreatic cancer, represent a significant global health burden.

Purpose Of The Study

To assess PTP-01's efficacy in targeting CSP within pancreatic tumors.
To estimate CSP density and tumor vascularity in pancreatic cancer.
To evaluate PTP-01 as a potential diagnostic or therapeutic agent for CSP-positive cancers.

Main Methods

Phase 0 clinical trial involving 3 pancreatic cancer patients.
Intravenous injection of <sup>111</sup>In-labeled PTP-01 (100 µg, 370 MBq).
Whole-body scintigraphy, SPECT imaging, and tissue biodistribution analysis 28 hours post-injection.

Main Results

PTP-01 administration was well-tolerated with no adverse events.
Significant PTP-01 uptake observed in kidneys, liver, and bladder, with notable tumor uptake.
Estimated CSP density of 10⁶ molecules per cell in tumors; elimination half-life ranged from 5 to 22 hours.

Conclusions

PTP-01 successfully targets CSP in pancreatic tumors, demonstrating the molecule's accessibility.
CSP is highly expressed on pancreatic tumors, comparable to established targets like Her2.
CSP represents a viable target for developing novel antibody-based therapies and antibody-drug conjugates for pancreatic cancer.

Keywords:

Cell Surface Plectin (CSP) Molecular imaging Pancreatic cancer Targeted therapy