1. Wp6: Cancer imaging with focus on breast cancer
FMT – XCT meeting, Heraklion, March 26th
Wp6: Cancer imaging with focus on breast cancer
Frederic DUCONGE, Anikitos GAROFALAKIS
Nicola MACKIEWIZC, Agnel CIBIEL
CEA, DSV, I2BM, SHFJ, LIME, INSERM U 803
Laboratoire d’imagerie de l’expression des gènes

2. Background Objectives of Wp6:
Phantoms is the standard way of evaluating an optical tomogrpher
Realistic conditions are achieved by the use of animal models
Objectives of Wp6:
To provide key fluorescence probes and cancer animal models
Quantitatively examine FMT performance to visualize disease processes in-vivo
To predict clinical utility

3. Overview
Animals models of breast cancer
cell lines, transgenic mouse models
Fluorescent probes
Instrumentation and measuremements
Conclusions

4. Mammary Tumor Xenografts
MDAMB-231 human breast adenocarcinoma cells (in RAG-1immunodeficient mice)
Well validated model for tumor growth and metastasis via over- expression of MT4-MMP (human Membrane Type-4 Matrix MetalloProteinases)
NIH-MEN2A
MCF-7 for probe development(aptamers)
U87MG brain tumor cell line

5. Mammary tumor transgenic models
Polyoma Middle T (PyMT) oncoprotein under the control of the Mouse Mammary Tumor Virus ‘Long Terminal Repeat’ (MMTV LTR).
Optical Imaging

6. Tumoral angiogenesis
- At the end of an avascular phase, the tumor has consumed most of nutrients available in its close environment. Then, most of the cancer cells are in a quiescent or necrotic state.
- To keep on growing, the tumor has to obtain new sources of nutrients: that is the angiogenic process.

7. Tumoral angiogenesis at a molecular level

8. Prosense 680 Fluorescent Probes Commercial probes
Integrinsense680 (VisenMedical, USA) AngioStamp (Fluoptics, France)
Cathepsin
activity
Integrin
localization
Custom-made probes
PEG nano-micelles
Unspecific
binding of
tumors

9. Tomographic(3D) Imaging

10. Preclinical imaging facilities at SHFJ center
Nuclear imaging
Optical imaging

11. Multimodality Imaging for intregrating the derived information
Glucose consumption related to Tumor volume(FDG)
Molecular information of tumor
related processes(Optical Probes)
Anatomical information

12. MDAMB-231/Prosense – Cathepsin activity
1 mm
Signal of optical in the surrounding tissue
90.84 %
Volume of tumor in the common area
27.86%

13. MDAMB-231/Prosense – Cathepsin activity
Longitudinal studies
3 h after injection
24 h
48 h
VOLUME (mm3)
MEAN VALUE (a.u.)
Prosense_1st Day
188
3.97
Prosense_2nd Day
302
3.45
Prosense_3rd Day
581
3.65

14. MDAMB-231/Integrisense – Integrin localization
1 mm
Integrin is found predominently in the base of the tumor
89.76 %
signal of optical in the surrounding tissue
11.48 %
volume of tumor in the common area

15. MDAMB-231/Nano micelle imaging
1 mm
68 ± 15 %
signal of optical in the surrounding area
17 ± 4 %
Optical volume in the common region

16. PC12/MEN2A/Prosense – Cathepsin activity
fusion
Opt
PET
66.5 ± 1.8 %
signal of optical in the surrounding area
31.8 ± 2.0 %
Optical volume in the common region
Volume
Mean
StdDev
Min
Max
Prosense_DAY_1
3.5
2.1
1.2
16.6
Prosense_DAY_2
412.45
0.9
15.0
Prosense_DAY_3
4.0
2.4
1. 1
13.0

17. fDOT/CT imaging of tumour angiogenesis using AngioStamp®
X-Ray CT
fDOT

18. fDOT/CT imaging of tumour angiogenesis using AngioStamp®

19. Integrisense and AngioStamp comparison
Integrisense 0h
Integrisense 3h
Tumor volume ~ 730 mm3
60,2 %
signal of optical in the surrounding
30,01
volume of tumor in the common area
31,42 %
signal of optical in the surrounding
32,55
volume of tumor in the common area
RAFT - RGD 2h
RAFT-RGD 0h
Tumor volume ~ 670 mm3
47,29 %
signal of optical in the surrounding
29,98
volume of tumor in the common area
36,2 %
signal of optical in the surrounding
36,48
volume of tumor in the common area

20. Mammary tumor transgenic mice models

21. Conclusions and perspectives
Development of a method for multimodal measurements on tumors
Characterization of important tumoral processes from complementary
PET/FMT/CT measurements
Different tumor cell lines and mouse models available for further testing
and comparison
Integration of microscopic information (Endoscopic imaging)
Development of Aptamer for specific Tumor labelling
Further experiments to complete the study

22. Advancement of programme
Planned Deliverables (month of delivery planned at start of first year)
6.1 To develop and characterize molecular probes (mo.9, 18)
6.2 Prepare and characterize mammary cancer animal models (mo.18)
6.3 Breed and making available PyMT animal models (mo.24)
6.4 Develop U87 animal models (mo.27)
6.5 Study and report the quantitative accuracy of FMT-alone and FMT-XCT in
resolving tumors (mo. 36)
6.6 Study and report cancer detection performance in various organs (mo. 40)
6.7 Report the overall imaging performance. (mo.42)
Status of achievement
 : achieved and continued.
6.4: to achieved
6.5: already started awaits comparison
: to begin after 6.5

23. Aknowledgements Experimental molecular imaging laboratory (LIME)
Bertrand Tavitian
Frédéric Ducongé
Raphael Boisgard
Abertine Dubois
Carine Pestourie