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Radiosynthesis and evaluation of novel [ 99m Tc(I)] + and [ 99m Tc(I)(CO) 3 ] + complexes with a 4‐nitroimidazole isocyanide for imaging tumor hypoxia
Author(s) -
Ruan Qing,
Zhang Xuran,
Zhang Junbo
Publication year - 2020
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.5798
Subject(s) - chemistry , biodistribution , isocyanide , radiosynthesis , radiochemistry , technetium , spect imaging , rhenium , tumor hypoxia , technetium 99m , nuclear chemistry , nuclear medicine , stereochemistry , positron emission tomography , scintigraphy , in vitro , inorganic chemistry , medicine , biochemistry , radiation therapy
[ 99m Tc(I)] + and [ 99m Tc(I)(CO) 3 ] + complexes with isocyanide exhibit high stability, which makes them suitable platforms to develop novel 99m Tc radiopharmaceuticals. To develop novel 99m Tc radiotracers for imaging hypoxia, in this study, a novel L ligand (4‐nitroimidazole isocyanide derivative) was synthesized and labelled using [ 99m Tc(I)] + core and [ 99m Tc(I)(CO) 3 ] + core to produce [ 99m Tc(L) 6 ] + and [ 99m Tc(CO) 3 (L) 3 ] + with high yields. To verify the structure of the 99m Tc complexes, corresponding rhenium analogues were synthesized and characterized. Both of the 99m Tc complexes were stable and hydrophilic. in vitro cellular uptake results showed they could exhibit good hypoxic selectivity. The evaluation of biodistribution in mice bearing S180 tumors indicated both of them could accumulate in tumor. Between them, [ 99m Tc(L) 6 ] + exhibited higher tumor uptake and tumor/non‐target ratio than [ 99m Tc(CO) 3 (L) 3 ] + . Further, single photon emission computed tomography (SPECT) imaging studies of [ 99m Tc(L) 6 ] + indicated an obvious accumulation in tumor and the value of the region‐of‐interest (ROI) ratio of the uptake for the tumor site to the corresponding non‐tumor region was 5.64 ± 0.52. The above results suggested [ 99m Tc(L) 6 ] + would be a potential tracer for imaging tumor hypoxia.