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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 6/2016

Open Access 01-12-2016 | Research Article

Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging

Authors: Marieke A. Stammes, Vicky T. Knol-Blankevoort, Luis J. Cruz, Hans R. I. J. Feitsma, Laura Mezzanotte, Robert A. Cordfunke, Riccardo Sinisi, Elena A. Dubikovskaya, Azusa Maeda, Ralph S. DaCosta, Katja Bierau, Alan Chan, Eric L. Kaijzel, Thomas J. A. Snoeks, Ermond R. van Beek, Clemens W. G. M. Löwik

Published in: Molecular Imaging and Biology | Issue 6/2016

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Abstract

Purpose

Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT). For this, the necrosis avid NIRF cyanine HQ4 was radiolabeled with 111indium, via the chelate diethylene triamine pentaacetic acid (DTPA).

Procedures

The necrosis avid properties of the radiotracer [111In]DTPA-HQ4 were examined in vitro and in vivo in different breast tumor models in mice using SPECT and optical imaging. Moreover, biodistribution studies were performed to examine the pharmacokinetics of the probe in vivo.

Results

Using optical imaging and radioactivity measurements, in vitro, we showed selective accumulation of [111In]DTPA-HQ4 in dead cells. Using SPECT and in biodistribution studies, the necrosis avidity of the radiotracer was confirmed in a 4T1 mouse breast cancer model of spontaneous tumor necrosis and in a MCF-7 human breast cancer model of chemotherapy-induced tumor necrosis.

Conclusions

The radiotracer [111In]DTPA-HQ4 possessed strong and selective necrosis avidity in vitro and in various mouse models of tumor necrosis in vivo, indicating its potential to be clinically applied for diagnostic purposes and to monitor anti-cancer treatment efficacy.
Appendix
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Metadata
Title
Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging
Authors
Marieke A. Stammes
Vicky T. Knol-Blankevoort
Luis J. Cruz
Hans R. I. J. Feitsma
Laura Mezzanotte
Robert A. Cordfunke
Riccardo Sinisi
Elena A. Dubikovskaya
Azusa Maeda
Ralph S. DaCosta
Katja Bierau
Alan Chan
Eric L. Kaijzel
Thomas J. A. Snoeks
Ermond R. van Beek
Clemens W. G. M. Löwik
Publication date
01-12-2016
Publisher
Springer US
Published in
Molecular Imaging and Biology / Issue 6/2016
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-016-0972-7

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