Preliminary studies of 99mTc-BnAO and its analogues: synthesis, radiolabeling and in vitro cell uptake

Sun, Xin; Chu, Taiwei; Wang, Xiangyun

doi:10.1016/j.nucmedbio.2009.09.003

« Previous Next »Nuclear Medicine and Biology
Volume 37, Issue 2 , Pages 117-123, February 2010

Preliminary studies of ^99mTc-BnAO and its analogues: synthesis, radiolabeling and in vitro cell uptake

Beijing National Laboratory for Molecular Sciences (BNLMS), Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

Received 10 July 2009; received in revised form 19 September 2009; accepted 28 September 2009. published online 04 November 2009.

Abstract

Introduction

^99mTc-BnAO is one of the nonnitroimidazole hypoxia markers with the highest citation and could be potentially useful in both oncology and other clinical applications. However, it appears inferior in vitro due to lower absolute accumulation and smaller anoxic/normoxic uptake ratio. It is possible that the analogues of ^99mTc-BnAO have higher hypoxia selectivity after the ligand of ^99mTc-BnAO is modified.

Methods

2,2′-(1,4-Diaminobutane)bis(2-methyl-3-butanone) dioxime (BnAO or HL91) and three novel analogues were synthesized and radiolabeled with technetium-99m. The cellular uptake of the radiolabeled complexes was determined in murine sarcoma S180 cell lines under anoxic and normoxic conditions.

Results

^99mTc-BnAO and its three novel analogues continuously accumulated in anoxic cells but not in normoxic ones, while the analogues showed earlier hypoxia selectivity and greater anoxic/normoxic differential.

Conclusions

The analogues are superior to ^99mTc-BnAO in terms of in vitro hypoxia selectivity and are viable candidates for further development as new nonnitroimidazole hypoxia markers in the future.

Keywords: BnAO, Labeling, Technetium-99m, Hypoxia marker, Lipophilicity, Cellular accumulation