Oferta TFM | ID 29

Introduction

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers worldwide, with limited treatment options and poor prognosis due to late diagnosis and aggressive tumor biology. ZIP4, a zinc transporter protein, has been identified as significantly overexpressed in PDAC and other malignancies, where it is associated with enhanced tumor growth, invasion, metastasis, and therapy resistance. These attributes make ZIP4 a promising molecular target for both diagnostic and therapeutic applications. To date, ZIP4 has been studied primarily through fluorescence-based imaging, which is limited by low tissue penetration, poor spatial resolution, and instability of the signal, constraints that severely restrict clinical translation.

Aim and Objectives

This project aims to explore the feasibility of targeting ZIP4 for non-invasive molecular imaging using immuno-positron emission tomography (immunoPET).

Methods

We will evaluate two candidate monoclonal antibodies targeting human ZIP4, which will serve as the basis for developing both antibody-based targeting agents and functionalized nanoparticles for diagnostic imaging and potential theranostic applications. These imaging agents will be thoroughly characterized to assess their chemical integrity, biochemical stability, binding affinity, and cellular binding dynamics using chemical characterization and fluorescence imaging techniques, immunocytochemistry and flow cytometry. Additionally, ZIP4 expression will be characterized and quantified in a cohort of human PDAC biopsy samples through immunohistochemistry, establishing clinical relevance. By the end of the project, we expect to generate well-characterized molecular imaging agents ready for radiolabeling with positron-emitting isotopes and subsequent in vivo evaluation in PDAC preclinical models.

Significance

This work is expected to result in the identification of one or more ZIP4-targeting antibodies or nanoparticle constructs that retain high affinity and specificity after chelator conjugation and are suitable for immunoPET applications. A successful outcome will provide proof-of-concept for ZIP4 as a viable target for non-invasive imaging in PDAC and support further development of targeted imaging probes. By transitioning ZIP4-targeting strategies from fluorescence-based approaches to immunoPET-compatible platforms, this work lays the groundwork for translational imaging technologies with high clinical relevance.