scFv-Fcs as a Radiotheranostic Platform for Targeting TRA-1-60 in Pancreatic Cancers.

Document Type

Article

Publication Date

8-25-2026

Publication Title

Research square

Abstract

PURPOSE: TRA-1-60 (TRA) is an established cancer stemness marker implicated in tumor initiation, therapeutic resistance, and disease relapse. It is minimally expressed in normal differentiated tissues, making it an appealing biomarker for immunopositron emission tomography (immunoPET) imaging and radiopharmaceutical therapy (RPT). Full-length monoclonal antibodies (mAbs) often exhibit prolonged circulation, which can lead to increased background signal and potential off-target radiation exposure to normal tissues, thereby raising concerns of blood-associated toxicity. To address these limitations, we developed a smaller TRA-targeted scFv-Fc antibody fragment and evaluated its potential as a unified immuno-theranostic platform for both noninvasive molecular imaging and targeted RPT of TRA

EXPERIMENTAL DESIGN: A TRA-specific scFv-Fc was conjugated with DFO-NCS and radiolabeled with zirconium-89 (t

RESULTS: [

CONCLUSIONS: We successfully established a TRA-targeted radiotheranostic platform which integrated immunoPET imaging and RPT using an scFv-Fc scaffold. This approach enables non-invasive diagnostic mapping of tumor-specific TRA expression and supports targeted delivery of therapeutic radiation with minimal organ toxicity while effectively suppressing both proliferative tumor subpopulations.

First Page

rs.3.rs-10592835

DOI

10.21203/rs.3.rs-10592835/v1

ISSN

2693-5015

PubMed ID

42687978

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