Disulfiram metabolite Cu(DDC)₂ enhances radionuclide uptake in vivo revealing insights into tumoural ablation resistance.

ABSTRACT:

Background

Exploitation of the sodium iodide symporter (NIS) has potentially broad clinical application across different tumour ablative settings but often fails in aggressive cancer due to diminished transport activity. We aimed to discover whether enhancing NIS function by modulating proteostasis was targetable in vivo, as well as the clinical relevance to radioiodide (RAI) treatment of patients with cancer.

Methods

We used 3D modelling, iterative design, reformulation, RAI uptake, RNA-Seq, cell surface biotinylation assays and NanoBRET in transformed cell lines and primary thyroid cells from patients to identify new drugs targeted at enhancing NIS function and to uncover their respective mechanisms. Systemic drug responses were monitored via ^99mTc pertechnetate

SUBMITTER: Brookes K 

PROVIDER: S-EPMC12917385 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature