Rhenium-186-labeled ortho-hydroxythiobenzhydrazide: a potential theranostic agent for use in metastatic breast cancer

Abstract

In this study, the aromatic thiobenzhydrazide derivative o-hydroxythiobenzhydrazide [H(htbh)] was radiolabeled with Rhenium-186 (¹⁸⁶Re) [t_1/2: 3.77 days, β_max: 1.07 MeV (71%), γ: 137 keV (9.47%)], produced in an in-house research reactor, yielding the [¹⁸⁶Re]Re-(htbh)₂ complex. The radiochemical purity (RCP) of the complex was found to be (98.07 ± 0.40)%. Mass spectroscopic analyses were used to elucidate the probable structure of the complex. The tumour targeting specificity of [¹⁸⁶Re]Re-(htbh)₂ was preliminarily assessed through in-vitro and in-vivo studies in preclinical models. While in-vitro studies included cell binding and internalization assays using MCF-7 cell lines, in vivo studies involved biodistribution analyses in SCID mice bearing MCF-7 induced human breast cancer xenografts. The pharmacokinetics revealed significant and prolonged tumour uptake, with SPECT/CT imaging showing plasma clearance within 24 hours and minimal retention in the liver and bladder.