Synthesis and Evaluation of Ga-68-Labeled Rhein for Early Assessment of Treatment-Induced Tumor Necrosis.

Abstract:

PURPOSE:This study aimed to synthesize a necrosis-avid agent using rhein as a precursor and labeled with gallium-68 (Ga-68) for positron emission tomography/computed tomography (PET/CT) imaging, to evaluate response to anticancer treatment in a mouse model. PROCEDURES:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated rhein was radiolabeled with Ga-68 to formulate [68Ga]DOTA-rhein. The in vitro stability of [68Ga]DOTA-rhein was assessed by radio-HPLC. Necrosis avidity was evaluated in a mouse model of muscle necrosis by microPET/CT imaging, biodistribution study, histochemical staining, and autoradiography studies. Murine tumor models with the subcutaneous implantation of S180 cell lines were generated for the evaluation of therapeutic effect. Tumor necrosis was induced by the treatment of combretastatin A4 disodium phosphate (CA4P), and microPET/CT imaging was performed at 1 h post tracer injection. DNA binding studies were conducted to explore the necrosis avidity mechanism of the tracer. RESULTS:[68Ga]DOTA-rhein exhibited a satisfactory yield, a radiochemical purity over 97 %, and a good serum stability. The uptakes of [68Ga]DOTA-rhein in necrotic muscles and tumors were significantly higher than those in normal muscles and tumors (P < 0.05). The results of autoradiography and histochemical staining were consistent with the selective uptake of the radiotracer in necrotic regions. MicroPET/CT images showed a high uptake of the tracer in necrotic muscles and necrotic tumors. DNA binding studies suggested that necrosis avidity correlated with DNA binding to a certain extent. CONCLUSIONS:Our results demonstrated that [68Ga]DOTA-rhein showed a prominent necrosis avidity and could be a useful probe for early assessment of response to anticancer therapy by PET/CT imaging.

journal_name

Mol Imaging Biol

authors

Zhang A,Wu T,Bian L,Li P,Liu Q,Zhang D,Jin Q,Zhang J,Huang G,Song S

doi

10.1007/s11307-019-01365-y

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

515-525

issue

3

eissn

1536-1632

issn

1860-2002

pii

10.1007/s11307-019-01365-y

journal_volume

22

pub_type

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