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Abstract: We describe a setup for LIBS mapping of nanoparticles and trace metallic elements in biological organ as well as the followed experimental procedure. Mapping was performed for metallic elements such as Gd, Si, Ca and Fe, with a resolution of 100μm on kidney slices sampled from a mouse 24h after intravenous injection of a solution of gadolinium-based nanoparticles. An approach for quantifying Gd in the tissue is also presented with a good agreement with measurement performed by ICP-OES. We demonstrate that LIBS offers a simple and robust method to study the distribution of gadolinium-based nanoparticles in biological samples, without any labeling of the nanoparticles. The used bench-top instrumentation is fully compatible with the standard optical microscopy, which shows its large potential use in Biology and Medicine as a tool for complementary observation of trace metallic elements with respect to the classical optical observations which are generally based on the responses of biomolecules or cells. [Copyright &y& Elsevier]

Background: Myocardial angiogenesis following reperfusion of an infarcted area may impact on patient prognosis and pro-angiogenic treatments are currently evaluated. The non-invasive imaging of angiogenesis would therefore be of potential clinical relevance in these settings. (99m)Tc-RAFT-RGD is a novel (99m)Tc-labeled tracer that targets the alpha(v)beta(3) integrin. Our objective was to determine whether this tracer was suitable for myocardial angiogenesis imaging.Methods and Results: A rat model of reperfused myocardial infarction was employed. Fourteen days following reperfusion, the animals were injected with (99m)Tc-RAFT-RGD or with its negative control (99m)Tc-RAFT-RAD. Fourteen animals were dedicated to autoradiographic imaging, infarct staining, and gamma-well counting of myocardial activity. In vivo dual-isotope pinhole SPECT imaging of (201)Tl and (99m)Tc-RAFT-RGD or (99m)Tc-RAFT-RAD was also performed in 11 additional animals. Neovessels were observed by immunostaining in the infarcted and peri-infarct areas. (99m)Tc-RAFT-RGD infarct-to-normal ratios by gamma-well counting and ex vivo imaging (2.5 +/- 0.6 and 4.9 +/- 0.9, respectively) were significantly higher than those of (99m)Tc-RAFT-RAD (1.7 +/- 0.2 and 2.2 +/- 0.4, respectively, P < .05). The infarcted area was readily visible in vivo by SPECT with (99m)Tc-RAFT-RGD but not with (99m)Tc-RAFT-RAD (infarct-to-normal zone activity ratio, 2.5 +/- 0.6 and 1.7 +/- 0.4, respectively, P < .05).Conclusion: (99m)Tc-RAFT-RGD allowed the experimental in vivo molecular imaging of myocardial angiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Early and accurate detection of tumors, like the development of targeted treatments, is a major field of research in oncology. The generation of specific vectors, capable of transporting a drug or a contrast agent to the primary tumor site as well as to the remote (micro-) metastasis would be an asset for early diagnosis and cancer therapy. Our goal was to develop new treatments based on the use of tumor-targeted delivery of large biomolecules (DNA, siRNA, peptides, or nanoparticles), able to induce apoptosis while dodging the specific mechanisms developed by tumor cells to resist this programmed cell death. Nonetheless, the insufficient effectiveness of the vectorization systems is still a crucial issue. In this context, we generated new targeting vectors for drug and biomolecules delivery and developed several optical imaging systems for the follow-up and evaluation of these vectorization systems in live mice. Based on our recent work, we present a brief overview of how noninvasive optical imaging in small animals can accelerate the development of targeted therapeutics in oncology. [Copyright &y& Elsevier]

Chemical elements play central roles for physiological homeostasis in human cells, and their dysregulation might lead to a certain number of pathologies. Novel imaging techniques that improve the work of pathologists for tissue analysis and diagnostics are continuously sought. We report the use of Laser-Induced Breakdown Spectroscopy (LIBS) to perform multi-elemental images of human paraffin-embedded skin samples on the entire biopsy scale in a complementary and compatible way with microscope histopathological examination. A specific instrumental configuration is proposed in order to detect most of the elements of medical interest (i.e. P, Al, Mg, Na, Zn, Si, Fe, and Cu). As an example of medical application, we selected and analysed skin biopsies, including healthy skin tissue, cutaneous metastasis of melanoma, Merkel-cell carcinoma and squamous cell carcinoma. Clear distinctions in the distribution of chemical elements are observed from the different samples investigated. This study demonstrates the high complementarity of LIBS elemental imaging with conventional histopathology, opening new opportunities for any medical application involving metals. [ABSTRACT FROM AUTHOR]

Résumé Depuis une vingtaine d’années, le développement de nanoparticules comprenant des éléments de haut numéro atomique comme agents radiosensibilisants est en plein essor. Le design de ces nano-objets doit respecter les contraintes « classiques » liées au développement de nanoparticules pour une application en oncologie, tout en permettant d’augmenter l’effet de la dose locale dans la zone tumorale en épargnant les tissus sains environnants. Dans ce cadre, l’injection intraveineuse de tel nanomédicament devient possible. Les différents points à prendre en considération pour la mise au point d’une nanoparticule administrable par voie systémique et possédant une activité radiosensibilisante seront discutés à partir de l’exemple de la nanoparticule AGuIX. Cette nanoparticule de quelques nanomètres de diamètre hydrodynamique, composée de polysiloxane et de chélates de gadolinium, a démontré son intérêt lors de nombreuses études précliniques et est en cours d’évaluation pour un essai clinique de phase I chez l’homme. En plus d’augmenter l’efficacité de la radiothérapie, elle peut être utilisée comme agent de contraste pour l’IRM et constitue donc un nanomédicament théranostique pour la médecine personnalisée. Since twenty years, many nanoparticles based on high atomic number elements have been developed as radiosensitizers. The design of these nanoparticles is limited by the classical rules associated with the development of nanoparticles for oncology and by the specific ones associated to radiosensitizers, which aim to increase the effect of the dose in the tumor area and to spare the health tissues. For this application, systemic administration of nanodrugs is possible. This paper will discuss the development of AGuIX nanoparticles and will emphasize on this example the critical points for the development of a nanodrug for this application. AGuIX nanoparticles display hydrodynamic diameters of a few nanometers and are composed of polysiloxane and gadolinium chelates. This particle has been used in many preclinical studies and is evaluated for a further phase I clinical trial. Finally, in addition to its high radiosensitizing potential, AGuIX display MRI functionality and can be used as theranostic nanodrug for personalized medicine. [ABSTRACT FROM AUTHOR]