Magnetically driven nanoparticles: ¹⁸FDG‐radiolabelling and positron emission tomography biodistribution study

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) have received increasing interest as contrast media in biomedical imaging and innovative therapeutic tools, in particular for loco-regional ablative treatments and drug delivery. The future of therapeutic applications would strongly benefit from improving the capability of the nanostructured constructs to reach the selected target, in particular beyond the intravascular space. Besides the decoration of SPIONs surface with ad hoc bioactive molecules, external magnetic fields are in principle able to remotely influence SPIONs' physiological biodistribution and concentrate them to a specific anatomical region or portion of a tissue. The reduction of SPIONs administered to the body and the need for defining the effective SPIONs local concentration suggest that PET/CT may be a method to quantitatively detect the nanoparticles accumulation in vivo at low concentration and assess their tridimensional distribution in response to an external magnetic field and in relation to the local anatomy highlighted by CT imaging. Here, we report on the possibility to assess the spatial distribution of magnetically-driven radiolabelled SPIONs in a peripheral tissue (mouse thigh) with microPET/CT imaging. To this aim we labelled SPIONs using F-2-fluoro-2-deoxyglucose as a synthon, by chemoselective oxime formation between its open-chain tautomer and nanoparticle amino-groups, and employed microPET/CT imaging to measure the radiolabelled construct biodistribution in a small animal model, following intravenous administration, with and without the application of a permanent magnet onto the skin. The in vivo and ex vivo results showed that micro-PET/CT was able to demonstrate the localizing action of the magnet on SPIONs and provide information, in a multimodal 3D data set, about SPIONs biodistribution taking into account the local anatomy. Copyright © 2017 John Wiley& Sons, Ltd.

Radiolabelling of nanomaterials for medical imaging and therapy

“…190 With this purpose, chemoselective oxime formation, alkyne-nitrone, copper catalysed azide-alkyne and azide-DBCO cycloadditions have been used for 18 F, 123 I and 125 I radiolabelling of both organic and inorganic nanomaterials. [191][192][193][194][195][196][197] As a main drawback, biorthogonal reactions require the control over the synthesis, characterisation and reactivity of two independent species, complicating their potential clinical translation. 11 C methylation reactions can be also applied for the radiolabelling of nanomaterials (Fig.…”

Iron oxide nanoparticles as multimodal imaging tools

“…uorescence mediated tomography, uorescence reectance tomography, optical coherence tomography, a large number of uorescence microscopies, ow cytometry, spectrophotometry, intra-vital microscopy, intravascular non-invasive near-infrared (NIRF) imaging, clinical endoscopy, and equipment for uorescence detection during surgery. Such method can be used for monitoring magnetofection efficacy, 60 for multi-modal imaging with MPI, MRI and PAI, 61,62 for detecting various biological entities such as tumors, 16,56 apoptotic cells, 7 and sentinel lymph nodes, 4 and for delineating inltrating tumors such as glioblastoma. 63…”

“…a tumor in case of 18 F-FDG that consumes more glucose than a healthy tissue. 53 Using IONP, it was possible to bring several improvement to the standard PET/SPECT imaging method by: (i) binding different radio-tracers to IONP [18F]uorodeoxyglucose (FDG), copper-61/64, gallium-66/68, zirconium-89, and iodine-124 for PET, 54 and 99mTc, 125I, 111I, 125I and 131I for SPECT, [54][55][56] that increase radio-tracer lifetime and targeting efficacy, 55 (ii) enabling simultaneous anatomical and functional imaging by combining PET/SPEC with MRI, taking advantage of the MRI contrasting ability of IONP, (iii) enlarging the SPECT/ PET imaging capacity to a therapeutic activity through the use of a theranostic IONP probe that can trigger drugs delivery, immunotherapy, hyperthermia, or photodynamic therapy. 19,57 In addition, PET/SPECT lead to high detection sensitivity, e.g.…”

Smart nanomaterials for cancer diagnosis and treatment

“…The usage in the form of nanofluids with external application of the magnetic field is predicted to generate enough heat postulated to produce adequate sensitivity and specificity to achieve clinical diagnostics and treatments effectively [ 130 ]. Moreover, the superparamagnetic nanoparticles (SPIONs) conjugated with radionuclides, such as 223Ra (radium-223), technetium-99 (99mTc), yttrium-90 (90Y), lutetium-177 (177Lu), 111In (índium-111), 59Fe (iron-59), and 18F-2-fluoro-2-deoxyglucose (18FDG) has substantially grown for biomedical applications [ 131 – 135 ]. Apart from inorganic nanomaterials, polymers, self-assembly amphiphilic micelles, core–shell nanoparticles, and lipids are commonly used in the thermo-responsive treatment of cancers.…”