Repurposing ¹⁸F-FMISO as a PET tracer for translational imaging of nitroreductase-based gene directed enzyme prodrug therapy.

ABSTRACT: Nitroreductases (NTR) are a family of bacterial enzymes used in gene directed enzyme prodrug therapy (GDEPT) that selectively activate prodrugs containing aromatic nitro groups to exert cytotoxic effects following gene transduction in tumours. The clinical development of NTR-based GDEPT has, in part, been hampered by the lack of translational imaging modalities to assess gene transduction and drug cytotoxicity, non-invasively. This study presents translational preclinical PET imaging to validate and report NTR activity using the clinically approved radiotracer, ¹⁸F-FMISO, as substrate for the NTR enzyme. Methods: The efficacy with which ¹⁸F-FMISO could be used to report NfsB NTR activity in vivo was investigated using the MDA-MB-231 mammary carcinoma xen

SUBMITTER: Ruiz de Garibay G 

PROVIDER: S-EPMC8058731 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature