A novel metal-based imaging probe for targeted dual-modality SPECT/MR imaging of angiogenesis

Superparamagnetic iron oxide nanoparticles with well-integrated multimodality imaging properties have generated increasing research interest in the past decade, especially when it comes to the targeted imaging of tumors. Bevacizumab (BCZM) on the other hand is a well-known and widely applied monoclonal antibody recognizing VEGF-A, which is overexpressed in angiogenesis. The aim of this proof-of-concept study was to develop a dual-modality nanoplatform for in vivo targeted single photon computed emission tomography (SPECT) and magnetic resonance imaging (MRI) of tumor vascularization. Iron oxide nanoparticles (IONPs) have been coated with dimercaptosuccinic acid (DMSA), for consequent functionalization with the monoclonal antibody BCZM radiolabeled with 99mTc, via well-developed surface engineering. The IONPs were characterized based on their size distribution, hydrodynamic diameter and magnetic properties. In vitro cytotoxicity studies showed that our nanoconstruct does not cause toxic effects in normal and cancer cells. Fe3O4-DMSA-SMCC-BCZM-99mTc were successfully prepared at high radiochemical purity (>92%) and their stability in human serum and in PBS were demonstrated. In vitro cell binding studies showed the ability of the Fe3O4-DMSA-SMCC-BCZM-99mTc to bind to the VEGF-165 isoform overexpressed on M-165 tumor cells. The ex vivo biodistribution studies in M165 tumor-bearing SCID mice showed high uptake in liver, spleen, kidney and lungs. The Fe3O4-DMSA-SMCC-BCZM-99mTc demonstrated quick tumor accumulation starting at 8.9 ± 1.88%ID/g at 2 h p.i., slightly increasing at 4 h p.i. (16.21 ± 2.56%ID/g) and then decreasing at 24 h p.i. (6.01 ± 1.69%ID/g). The tumor-to-blood ratio reached a maximum at 24 h p.i. (~7), which is also the case for the tumor-to-muscle ratio (~18). Initial pilot imaging studies on an experimental gamma-camera and a clinical MR camera prove our hypothesis and demonstrate the potential of Fe3O4-DMSA-SMCC-BCZM-99mTc for targeted dual-modality imaging. Our findings indicate that Fe3O4-DMSA-SMCC-BCZM-99mTc IONPs could serve as an important diagnostic tool for biomedical imaging as well as a promising candidate for future theranostic applications in cancer

Solid-State Detectors for Small-Animal Imaging - Molecular Imaging of Small Animals

Semiconductor detector technology, initially developed for high energy physics applications, has found a distinctive role in high performance systems for X-ray and gamma-ray medical imaging applications, including small animal imaging. Single-Photon Emission Computed Tomography (SPECT) small animal imaging requires the development of compact detectors with intrinsically ultrahigh spatial resolution, high energy resolution and good detection efficiency, in addition to suitable radiation collimation strategies. This overall performance can only partly be guaranteed by scintillator based systems with photomultiplier tube readout, the most used technology at present for small animal SPECT scanners. On the other hand, with respect to scintillator based detectors, semiconductor detectors can offer a gain by approximately a factor two in energy resolution at typical radionuclide energies, a factor greater than two in intrinsic spatial resolution, and a comparable intrinsic detection efficiency, though usually at a reduced field of view. Moreover, their compactness could be crucial in devising animal “personalized” miniature scanners. An additional interesting feature of semiconductor based small animal SPECT scanners is that the detector technology can be used both for gamma-ray imaging and for X-ray imaging, when coupling the SPECT scanner to a low resolution X-ray CT scanner for anatomical registration. The requirement of high spatial resolution, coupled to high sensitivity, becomes also stringent in microPET systems, where semiconductor detectors could be the technology of choice for future high performance PET scanners

High-Resolution and Animal Imaging Instrumentation and Techniques

During the last decade we have observed a growing interest in “in vivo” imaging techniques for small animals. This is due to the necessity of studying biochemical processes at a molecular level for pharmacology, genetic, and pathology investigations. This field of research is usually called “molecular imaging.”Advances in biological understanding have been accompanied by technological advances in instrumentation and techniques and image-reconstruction software, resulting in improved image quality, visibility, and interpretation. The main technological challenge is then the design of systems with high spatial resolution and high sensitivity. This chapter gives a short overview of the state-of-the-art technologies for high-resolution and high-sensitivity molecular imaging techniques, namely, positron emission tomography (PET) and single photon emission computed tomography (SPECT) as well as the basics of small-animal x-ray computed tomography (CT). Multimodality techniques merging molecular information with anatomical details are also introduced. Finally, the new trends in detector technology for other high-resolution applications like breast cancer investigation are presented