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

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 ¹¹¹In-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.