Abstract

Radiolabeled magnetic nanoparticles are promising candidates as dual-modality-contrast-agents (DMCA) for diagnostic applications. The immunocompatibility of a new DMCA is a prerequisite for subsequent in vivo applications. Here, a new DMCA, namely Fe3O4 nanoparticles radiolabeled with 68Ga, is subjected to immunocompatibility tests both in vitro and in vivo. The in vitro immunocompatibility of the DMCA relied on incubation with donated human WBCs and PLTs (five healthy individuals). Optical microscopy (OM) and atomic force microscopy (AFM) were employed for the investigation of the morphological characteristics of WBCs and PLTs. A standard hematology analyzer (HA) provided information on complete blood count. The in vivo immunocompatibility of the DMCA was assessed through its biodistribution among the basic organs of the mononuclear phagocyte system in normal and immunodeficient mice (nine in each group). In addition, Magnetic Resonance Imaging (MRI) data were acquired in normal mice (three). The combined OM, AFM and HA in vitro data showed that although the DMCA promoted noticeable activation of WBCs and PLTs, neither degradation nor clustering were observed. The in vivo data showed no difference of the DMCA biodistribution between the normal and immunodeficient mice, while the MRI data prove the efficacy of the particular DMCA when compared to the non-radiolabeled, parent CA. The combined in vitro and in vivo data prove that the particular DMCA is a promising candidate for future in vivo applications.

Highlights

  • Radiolabeled magnetic nanoparticles are promising candidates as dual-modality-contrast-agents (DMCA) for diagnostic applications

  • Dual modality contrast agents (DMCA), such as radiolabeled iron oxide nanoparticles (IONPs), are promising candidates in imaging applications since they combine the advantages of two different imaging modalities, for example of Positron Emission Tomography (PET) and/or Single-Photon Emission Computed Tomography (SPECT) with Magnetic Resonance Imaging (MRI) in a way that the obtained results are superior to the sum of those of the two former imaging techniques

  • Panels (B)(i)–(D)(i) focus on white blood cells (WBCs) in activated state of the respective panels (B)–(D), coming from DMCA-free after 120 min incubation (panel (B)(i)) and DMCA-incubated for 120 min samples at ­CDMCA = 0.1 mg/ml(panel (C)(i)) and at C­ DMCA = 1 mg/ml (panel (D)(i)) that show the progression of shape transformation from a simple polarized form (panel (B)(i)) to a complex ruffled shape (panel (D)(i))

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Summary

Introduction

Radiolabeled magnetic nanoparticles are promising candidates as dual-modality-contrast-agents (DMCA) for diagnostic applications. Before the use of a new DMCA in diagnostic applications, the investigation of its biocompatibility with the aforementioned human blood cells should be a principal concern, in order to avoid any potential side effect that could be hazardous for in vivo use. For this reason, various immunological studies have been reported in the literature highlighting the impact of nanoparticles with different physico-chemical properties (i.e. size, shape, surface charge etc.) on the WBCs and ­PLTs8–16. Referring to the in vivo evaluation, we studied the accumulation of the DMCA on the basic organs of the mononuclear phagocyte system, namely liver, spleen and lungs, by injecting a standard DMCA dose via the tail vein in nine normal and nine immunodeficient mice

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