99mTc-Labeled Iron Oxide Nanoparticles as Dual-Modality Contrast Agent: A Preliminary Study from Synthesis to Magnetic Resonance and Gamma-Camera Imaging in Mice Models

Abstract

The combination of two imaging modalities in a single agent has received increasing attention during the last few years, since its synergistic action guarantees both accurate and timely diagnosis. For this reason, dual-modality contrast agents (DMCAs), such as radiolabeled iron oxide (namely Fe3O4) nanoparticles, constitute a powerful tool in diagnostic applications. In this respect, here we focus on the synthesis of a potential single photon emission computed tomography/magnetic resonance imaging (SPECT/MRI) DMCA, which consists of Fe3O4 nanoparticles, surface functionalized with 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD) and radiolabeled with 99mTc, [99mTc]Tc-DPD-Fe3O4. The in vitro stability results showed that this DMCA is highly stable after 24 h of incubation in phosphate buffer saline (~92.3% intact), while it is adequately stable after 24 h of incubation with human serum (~67.3% intact). Subsequently, [99mTc]Tc-DPD-Fe3O4 DMCA was evaluated in vivo in mice models through standard biodistribution studies, MR imaging and gamma-camera imaging. All techniques provided consistent results, clearly evidencing noticeable liver uptake. Our work documents that [99mTc]Tc-DPD-Fe3O4 has all the necessary characteristics to be a potential DMCA.

Gamma-Camera Direct Imaging of the Plasma and On/Intra Cellular Distribution of the 99mTc-DPD-Fe3O4 Dual-Modality Contrast Agent in Peripheral Human Blood

“…All reagents and solvents used for radiolabeling of DPD-Fe 3 O 4 with 99m Tc and the appropriate equipment employed to determine its radiolabeling yield are described in detail in the respective section of our previous study, which can be found in [36].…”

Radiolabeled Iron Oxide Nanoparticles as Dual Modality Contrast Agents in SPECT/MRI and PET/MRI

“…Karageorgou et al [ 40 ] have focused on the synthesis and subsequent in vitro and in vivo evaluation of RIONs for dual imaging with SPECT and MRI. The RIONs consist of 99m Tc radiolabeled and 2,3-dicarboxypropane-1,1-diphosphonic acid coated IONs ( Figure 4 a).…”

“…For both media (PBS and human serum), the stability results are determined by thin layer chromatographic analysis, using acetone and citrate solution (0.1 M) as the mobile phases. In the case of the stability of RIONs in human serum, the acetone-developed chromatograms show no release of free 99m Tc from the RIONs incubated in human serum for up to 24 h [ 40 ]. According to the authors, the slight decrease observed (67.3%) is expected due to the presence of serum proteins that may bind 99m Tc, ultimately affecting the original DMCA [ 40 ].…”

“…In the case of the stability of RIONs in human serum, the acetone-developed chromatograms show no release of free 99m Tc from the RIONs incubated in human serum for up to 24 h [ 40 ]. According to the authors, the slight decrease observed (67.3%) is expected due to the presence of serum proteins that may bind 99m Tc, ultimately affecting the original DMCA [ 40 ]. As far as the in vivo evaluation is concerned, both biodistribution ( Figure 4 b) and imaging studies (namely, MRI ( Figure 4 c–h) and gamma-camera ( Figure 4 i)) have been performed in normal Swiss mice, showing consistent results by demonstrating noticeable liver uptake of the RIONs.…”

“…The areas of interest, that is, the liver and spleen, are demonstrated by the dotted red lines; ( i ) Representative coronal image of a mouse injected with RIONs obtained at 4 h p.i. by gamma camera [ 40 ].…”