Synthesis and evaluation of [99mTcN]2+ core and [99mTcO]3+ core labeled complexes with 4-nitroimidazole xanthate derivative for tumor hypoxia imaging

Qing Ruan; Xuran Zhang; Qianqian Gan; Si'an Fang; Junbo Zhang

doi:10.1016/j.bmcl.2020.127582

Synthesis and evaluation of [^99mTcN]²⁺ core and [^99mTcO]³⁺ core labeled complexes with 4-nitroimidazole xanthate derivative for tumor hypoxia imaging

Bioorg Med Chem Lett. 2020 Nov 15;30(22):127582. doi: 10.1016/j.bmcl.2020.127582. Epub 2020 Sep 28.

Authors

Qing Ruan¹, Xuran Zhang¹, Qianqian Gan¹, Si'an Fang¹, Junbo Zhang²

Affiliations

¹ Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
² Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China. Electronic address: [email protected].

PMID: 33002601
DOI: 10.1016/j.bmcl.2020.127582

Abstract

A 4-nitroimidazole xanthate ligand (NMXT) was synthesized and radiolabeled with [^99mTcN]²⁺ core and [^99mTcO]³⁺ core to obtain ^99mTcN-NMXT and ^99mTcO-NMXT, respectively. The two ^99mTc-complexes were prepared with high radiochemical purity and had good stability. The partition coefficient results indicated both of them were hydrophilic, and cellular uptake studies showed they exhibited good hypoxic selectivity. From the biodistribution study results, ^99mTcO-NMXT showed more favourable tumor uptake (1.73 ± 0.14 ID%/g) and higher tumor/muscle ratio (7.01 ± 0.16) than ^99mTcN-NMXT at 4 h post-injection. Single photon emission computed tomography (SPECT) imaging study of ^99mTcO-NMXT showed there was a visible accumulation in tumor site, suggesting it would be a promising candidate as a tumor hypoxia imaging agent.

Keywords: (99m)Tc; Hypoxia; Nitroimidazole; SPECT imaging; Tumor; Xanthate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Mice
Mice, Inbred Strains
Neoplasms, Experimental / diagnostic imaging
Nitroimidazoles / chemistry*
Organotechnetium Compounds / chemical synthesis*
Organotechnetium Compounds / pharmacokinetics
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / chemistry*
Radiopharmaceuticals / pharmacokinetics
Sarcoma / diagnostic imaging*
Tissue Distribution
Tomography, Emission-Computed, Single-Photon
Tumor Hypoxia

Substances

Nitroimidazoles
Organotechnetium Compounds
Radiopharmaceuticals
4-nitroimidazole