Format

Send to

Choose Destination
Mol Imaging Biol. 2016 Dec;18(6):905-915.

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

Author information

1
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
2
Percuros BV, Leiden, The Netherlands.
3
Department of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands.
4
Department of Radiology, Erasmus Medical Center, Building-room: Na606, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
5
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
6
Institute of Chemical Sciences and Engineering (ISIC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
7
Division of Biophysics and Bioimaging, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
8
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
9
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. c.lowik@erasmusmc.nl.
10
Department of Radiology, Erasmus Medical Center, Building-room: Na606, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. c.lowik@erasmusmc.nl.

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.

KEYWORDS:

Cancer; Cyanine; Multimodal imaging; Necrosis avid contrast agent; Radiolabeling

PMID:
27277828
PMCID:
PMC5093207
DOI:
10.1007/s11307-016-0972-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center