A Phase 0, Open Label Study to Evaluate the Biodistribution and Pharmacokinetics of a Single Intravenous Bolus Dose of PTP-01 in Subjects With Resectable Pancreatic Ductal Adenocarcinoma

The purpose of this clinical trial is to study an experimental drug called PTP-01 that is being used as an imaging agent to diagnosis pancreatic cancer. Currently, pancreatic cancer is diagnosed using CT or MRI scans which miss small pancreatic cancers, particularly early stage disease. Researchers at the University of Virginia have identified a biomarker for pancreatic cancer called plectin, which is very specific for pancreatic cancer and not other, non-cancerous conditions involving the pancreas. These researchers have also developed PTP-01, an experimental drug that may be used with SPECT imaging to detect pancreatic cancer cells in humans.

开始日期2013-11-01

申办/合作机构

University of Virginia

100 项与 PTP-01 相关的临床结果

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100 项与 PTP-01 相关的转化医学

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100 项与 PTP-01 相关的专利（医药）

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项与 PTP-01 相关的文献（医药）

MOLECULAR IMAGING AND BIOLOGY

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

Article

作者: Dimastromatteo, Julien ; Kelly, Kimberly A ; He, Jiang ; Adams, Reid B

Abstract:

Purpose:

Plectin is traditionally an intracellular cytoskeletal protein that maintains cell structure and stability. However, we and others have identified its surface-localized form in cancer (CSP), where it influences cell adhesion, migration, immune response, and tumor signaling. CSP-positive tumors (pancreatic, lung, ovarian, and breast cancers) contribute to over 3 million annual deaths, highlighting its clinical relevance. This phase 0 study aimed to evaluate PTP-01’s ability to target CSP in pancreatic tumors, despite their dense desmoplastic stroma, and to estimate CSP density and tumor vascularity.

Methods:

Pancreatic cancer patients (n = 3) received an intravenous injection of 100 µg PTP-01 labeled with 370 MBq 111In one day before resection. Whole-body planar scintigraphy and SPECT imaging were performed at multiple time points. Resected tumors and adjacent tissues were collected 28 h post-injection. Blood and urine samples were obtained for pharmacokinetic analysis. Tissue biodistribution was assessed using whole-body SPECT scans.

Results:

PTP-01 injection caused no reported adverse events. Uptake was primarily observed in the kidneys, liver, and bladder, with some tumor uptake. CSP density in tumors was estimated at 10⁶ molecules per cell. The elimination half-life (T₁/₂) ranged from 5 to 22 h across patients.

Conclusion:

PTP-01 imaging of pancreatic tumors revealed the ability of a targeted agent to bind to CSP. Further, CSP density in tumors was estimated to be on par with other surface molecules such as Her2 with effective targeted therapies. This study suggests that CSP is a highly expressed, accessible molecule for the development of targeted therapies such as antibodies or antibody–drug conjugates.

100 项与 PTP-01 相关的药物交易

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