Cyclopharma Laboratoires

France

Cyclopharma Laboratoires

France
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Lacoeuille F.,University of Angers | Hindre F.,University of Angers | Denizot B.,University of Angers | Bouchet F.,University of Angers | And 5 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2010

Purpose: In order to avoid the microbiological risks linked to human serum albumin macroaggregates (MAA) used for lung perfusion scintigraphy, we developed a new starch-based Tc-99m potential radiopharmaceutical. Methods: Microparticles were prepared from oxidised starch coupled to natural polyamine for Tc-99m complexation. Suspensions were formulated as ready-to-use kits for easy one-step labelling procedures. Results: Particle-size analysis, electron microscopy, and confocal microscopy were performed for microparticle characterisation, and gave a typical size distribution ranging from 7 to 63 μm, with a homogenous population of spherical or oval-shaped microparticles. Radiochemical purity exceeded 95%, and was stable for at least 8 h. When challenged with histidine and human plasma, labelling was also stable. Dynamic scintigraphic acquisitions and biodistribution studies conducted on healthy Wistar rats showed a tracer accumulation with more than 80% of the ID in the lungs after 15 min. Conclusions: With clinically significant characteristics such as a lung half-life of 3 h, a lung-to-vascular ratio of 900, and a lung-to-liver ratio of 90, starch-based microparticles exhibit all the qualities for an effective new lung perfusion agent. © 2009 Springer-Verlag.


Miot-Noirault E.,French Institute of Health and Medical Research | Guicheux J.,University of Nantes | Vidal A.,French Institute of Health and Medical Research | Gauthier O.,University of Nantes | And 6 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2012

Purpose: A rabbit model of osteochondral defects (OD) and spontaneous healing was longitudinally followed over 12 weeks, by in vivo joint scintigraphy using 99mTc-NTP 15-5, and histology. Methods: We used two models, one with one OD (OD1 group) in the femoral condyle of one knee and the other with two ODs (OD2 group) in the femoral condyle of one knee, with the contralateral knees serving as the reference. A serial longitudinal imaging study was performed with the scintigraphic ratio (SR, operated knee uptake/contralateral knee uptake) determined at each time-point. Results: ODs were imaged as radioactive defects. The SR was decreased with respective to controls, with values of 0.73±0.08 and 0.65±0.07 in the OD1 and OD2 groups, respectively, at 4 weeks after surgery. Histology of both OD groups revealed the presence of repair tissue characterized by a small amount of sulphated glycosaminoglycans and collagen. Conclusion: 99mTc-NTP 15-5 imaging provided quantitative criteria useful for in vivo evaluation of cartilage trauma and healing. © 2012 Springer-Verlag.


Miot-Noirault E.,French Institute of Health and Medical Research | Peyrode C.,French Institute of Health and Medical Research | Gouin F.,University of Nantes | Vidal A.,French Institute of Health and Medical Research | And 7 more authors.
Sarcoma | Year: 2011

Our lab developed 99mTc-NTP 15-5 radiotracer as targeting proteoglycans (PGs) for the scintigraphic imaging of joint. This paper reports preclinical results of 99mTc-NTP 15-5 imaging of an orthotopic model of Swarm rat chondrosarcoma (SRC). 99mTc-NTP 15-5 imaging of SRC-bearing and sham-operated animals was performed and quantified at regular intervals after surgery and compared to bone scintigraphy and tumoural volume. Tumours were characterized by histology and PG assay. SRC exhibited a significant 99mTc-NTP 15-5 uptake at very early stage after implant (with tumour/muscle ratio of 1.61 ± 0.14), whereas no measurable tumour was evidenced. As tumour grew, mean tumour/muscle ratio was increased by 2.4, between the early and late stage of pathology. Bone scintigraphy failed to image chondrosarcoma, even at the later stage of study. 99mTc-NTP 15-5 imaging provided a suitable set of quantitative criteria for the in vivo characterization of chondrosarcoma behaviour in bone environment, useful for achieving a greater understanding of the pathology. Copyright © 2011 Caroline Peyrode et al.


Lacoeuille F.,French Institute of Health and Medical Research | Lacoeuille F.,Angers University Hospital Center | Hindre F.,French Institute of Health and Medical Research | Venier-Julienne M.C.,French Institute of Health and Medical Research | And 11 more authors.
Biomaterials | Year: 2011

The aim of this work was to develop a new microparticulate system able to form a complex with radionuclides with a high yield of purity for diagnostic or therapeutic applications. Owing to its properties potato starch was chosen as starting material and modified by oxidization and coupling of a ligand (polyamine) enabling modified starch to chelate radionuclides. The choice of suitable experiments was based on a combination of a Rechtschaffner experimental design and a surface response design to determine the influence of experimental parameters and to optimize the final product. Starch-based microparticle formulations from the experimental plans were compared and characterized through particle size analysis, scanning electron microscopy, elemental analysis and, for the most promising formulations, by in vitro labeling stability studies and determination of free polyamine content or in vivo imaging studies. The mechanism of starch-based microparticle degradation was identified by means of size measurements. The results of the Rechtschaffner design showed the positive qualitative effect of the temperature and the duration of coupling reaction whereas surface response analysis clearly showed that, by increasing the oxidization level and starch concentration, the nitrogen content in the final product is increased. In vitro and in vivo characterization led to identification of the best formulation. With a size around 30 μm, high radiochemical purity (over 95%) and a high signal-to-noise ratio (over 600), the new starch-based microparticulate system could be prepared as ready-to-use kits and sterilized without modification of its characteristics, and thus meet the requirement for in vivo diagnostic and therapeutic applications. © 2011 Elsevier Ltd.

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