Research
IPAM

Montpellier Small organism imaging (IPAM) - www.ipam.cnrs.fr - BioCampus

 
Objectives

 

IRCM core facility offers different imaging modalities that are complementary, and allow support for various programs in life science such as oncology, immunology, cardiology, neurobiology, embryonic development, etc.

Altogether, IRCM equipments provide functional, anatomical and molecular information. All our systems allow non invasive longitudinal in vivo studies useful to follow the development and progression of pathologies and the long-term effect of drugs.

 

Equipment

 

Our imaging expertise includes all the latest and most powerful imaging systems, such as non invasive bioluminescence and fluorescence imaging systems and a nano-SPECT/CT that allows in vivo 3D scintigraphy.

 

Bioluminescent Imaging System

 

Reporter genes are commonly used to visualize gene expression in vivo in a non-invasive manner. It is the method of choice to measure, in living preclinical model, the activity of new molecules and to assess the efficacy of cancer treatments. A lot of applications using several luciferase and photoproteins as reporter genes have been developed in our laboratories. These cellular models can be grafted to immunodeficient preclinical model (Nude or Scid), and used to study the therapeutic effects of treatments on tumor growth.

The imaging is realized on anesthetised living preclinical model using a CCD camera after substrate injection. The experiment can be realized daily and thus allows the realisation of kinetic tumour development or the response to a drug administration.
 

Nano-SPECT/CT

 

The combined SPECT/CT system is directly derived from the medical imaging technology and allows the acquisition and superposition of functional molecular images (SPECT) and morphological images (CT).

SPECT (Single Photon Emission Tomography)is an imaging technique widely used for humans. It is based on the in vivo detection of a “vector” molecule with a strong affinity for some cells, an organ or a system, coupled to a “tracing” radioactive g-isotope that allows visualising the uptake of the vector in the organism. The set-up and development of the SPECT/CT facilities are realised in partnership with specialists in nuclear medicine and radiotherapy.

The combination of SPECT and CT represents both a functional and metabolic imaging system, because it allows the analysis of the functioning or of the metabolism of a tissue or an organ, and a molecular imaging system that allows the visualisation of the interaction of a ligand (hormone, peptide, antibody) with its partner (receptor, nucleic acid).

The tomo-densitometry X (TDM/CT) provides morphological and anatomical images of the skeleton and/or organs in the same conditions as for human use. TDM/CT is a precious tool for the analysis of bone and some soft tissues (i.e., lung, kidney) with a very good infra-millimetric resolution. Concerning the bone, it is particularly appropriate for the study of the metastasis of some cancers and of the damage due to arthritis. In combination with SPECT, it allows the readjustment of images and engenders a better anatomical localisation of the area of uptake of a radiopharmaceutical. In combination the two systems constitute a particularly powerful tool that provides images of anatomo-functional fusion.

 

Finally, physiological monitoring of preclinical model subjected to a gas anesthesia (isoflurane).is realized with a respiratory and heart gating of preclinical model

 

All our imaging systems are located in a pathogen-free preclinical platform, and in restricted areas. preclinical model are thus housed in better health conditions. Depending on the protocol, they are housed in ventilated caging systems, rigid isolator coupled to a PSM when of use of a volatile radioelement, or lead-animal-housing system when using highly energetic radio-element. This preclinical model caging system (LemerPax ®) allows housing of preclinical model treated with radiotherapy, and this without interfering with other experiments but also without risk to the experimenter. In addition, an analyzer blood cell abnormalities (ScilVet-ABC ®) allows the physiological monitoring of preclinical model.

 

 

Research areas

 

In partnership with IRCM groups, the platform is increasing the number of bioluminescent cell models and is improving their sensitivity and specificity of detection. These new cell line models are then implanted in immmuno-deficient preclinical model, ectopically or orthotopically, and used to study the effects of different treatments on the attachment and growth of the tumours.

 

In addition, the platform expand this optical imaging technique towards the fluorescent imaging in which cells and organs are visualised through the expression of fluorescent proteins. This technique has been limited for a long time by the excitable wavelength of these molecules in the green that caused an important auto-fluorescence in the tissues; however, now it can benefit of proteins that are excited in the red. This allows both a reduction of the auto-fluorescence and a deeper analysis of the chosen phenomenon, even though the fluorescence remains essentially a surface technique (a few millimetres).

 

Most of the physiological functions can be explored by SPECT, like, for example, kidney (glomerular filtration with 99mTc-DTPA, tubular secretion with 123I-Hippuran), heart (myocardial perfusion with 99mTc-Cardiolite®, ventricular kinetics with 99mTc-hématies), lung (capillary perfusion with 9mTc-albumin micro-spheres), hepato-digestive (biliary kinetics with 99mTc-HIDA, gastro-oesophageal transit with a radioactive bolus), thyroid (kinetics with 123I or 131I), brain (brain perfusion with 99m Tc-HMPAO, neurotransmission with 123I.

 

Datscan® functions

 

Similarly, the applications in oncology are numerous going from the specific detection of tumours by means of antibodies or ligands of receptors (i.e., colorectal cancer with 99mTc-AC-anti-CEA, breast cancer with 111In-Herceptine, neuro-endocrine tumours with 99mTc-Octreoscan®, bronchial cancers with 99mTc-Neospect®, pheocromocytome with 123I-MIBG), to the detection of bone metastases (99mTc-diphosphonate), the assessment of tumour activity (201Thallium), the measurement of apoptosis (9mTc-Annexin V), or the study of neo-angiogenesis (99mTc-RGD).

 

SPECT-CT permits also the estimate, by using models of the Monte-Carlo type, of the dose, which is delivered to the tumour and to the healthy tissue, during the experimental phases of metabolic radiotherapy.

 

Prestations

 

1. User training to autonomy for optical imaging

2. Optical imaging studies on small preclinical model (bioluminescence and fluorescence)

3. Screening of nuclear receptor ligand activity, non-invasive in vivo imaging of tumor growth, tumor metastasis monitoring, studies of therapies

4. Non-invasive in vivo imaging scintigraphic studies biodistributions, comparison of the uptake of different radiotracers directed on the same target

5. Radiographic imaging μCT, with or without a contrast agent

 

Publications

 

Arsic N, Gadea G, Lagerqvist EL, Busson M, Cahuzac N, Brock C, Hollande F, Gire V, Pannequin J, Roux P.
The p53 isoform Δ133p53β promotes cancer stem cell potential.
Stem Cell Reports. 2015 Apr 14;4(4):531-40. doi: 10.1016/j.stemcr.2015.02.001. Epub 2015 Mar 5.

 

Vives V, Cres G, Richard C, Busson M, Ferrandez Y, Planson AG, Zeghouf M, Cherfils J, Malaval L, Blangy A.
Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation.
Nat Commun. 2015 Feb 3;6:6218. doi: 10.1038/ncomms7218.

 

Contact

 

Institut de Recherche en Cancérologie de Montpellier

CRLC Val d'Aurelle - Paul Lamarque

208 rue des Apothicaires

34298 Montpellier cedex 5 FRANCE

 

Tel : 33.(0)4.67.61.24.10

 

 

 


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