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Synthesis and Evaluation of Diindole-Based MRI Contrast Agent for In Vivo Visualization of Necrosis.

Abstract：

PURPOSE:Noninvasive imaging of cell necrosis can provide an early evaluation of tumor response to treatments. Here, we aimed to design and synthesize a novel diindole-based magnetic resonance imaging (MRI) contrast agent (Gd-bis-DOTA-diindolylmethane, Gd-DIM) for assessment of tumor response to therapy at an early stage. PROCEDURES:The oil-water partition coefficient (Log P) and relaxivity of Gd-DIM were determined in vitro. Then, its necrosis avidity was examined in necrotic cells in vitro and in rat models with microwave ablation-induced muscle necrosis (MAMN) and ischemia reperfusion-induced liver necrosis (IRLN) by MRI. Visualization of tumor necrosis induced by combretastatin A-4 disodium phosphate (CA4P) was evaluated in rats bearing W256 orthotopic liver tumor by MRI. Finally, DNA binding assay was performed to explore the possible necrosis-avidity mechanism of Gd-DIM. RESULTS:The Log P value and T1 relaxivity of Gd-DIM is - 2.15 ± 0.01 and 6.61 mM-1 s-1, respectively. Gd-DIM showed predominant necrosis avidity in vitro and in vivo. Clear visualization of the tumor necrosis induced by CA4P was achieved at 60 min after administration of Gd-DIM. DNA binding study indicated that the necrosis-avidity mechanism of Gd-DIM may be due to its binding to exposed DNA in necrotic cells. CONCLUSION:Gd-DIM may serve as a promising necrosis-avid MRI contrast agent for early assessment of tumor response to therapy.

journal_name

Mol Imaging Biol

journal_title

Molecular imaging and biology

authors

Zhang L,Liu L,Zhang D,Jin Q,Gao M,Wu T,Feng Y,Ni Y,Yin Z,Zhang J

doi

10.1007/s11307-019-01399-2

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

593-601

issue

3

eissn

1536-1632

issn

1860-2002

pii

10.1007/s11307-019-01399-2

journal_volume

22

pub_type

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