Presentation by Nynke van den Berg, PhD candidate at the Interventional Molecular Imaging group at Radiology, LUMC, for the Science meets Business café of 9 October 2014. This event was held in the BioPartner 1 foyer in Leiden. For the report, see http://www.sciencemeetsbusiness.nl/9-oct-2014/

1. How hybrid tracers may help change treatment
paradigms and open up new commercial avenues
Nynke S. van den Berg1,2, Tessa Buckle1, and Fijs W.B. van
Leeuwen1,2
1. Department of Radiology, LUMC, Leiden
2. Department of Urology, NKI-AvL, Amsterdam

2. Find out what is wrong and take it out?!
Intervention
Diagnostics

3. Anatomical Imaging
MRI
US
Functional
Imaging
X-ray fluoscopy Navigation
perfusion CT
Molecular Imaging
PET
Gamma imaging
CT
CE US
Luminescence imaging
Modalities for in-depth
imaging
Positron imaging
Modalities for superficial
imaging
van Leeuwen et al.,, Accepted for publication in Radiology 2014

4. Can we combine various imaging technologies to allow for an
integrated pre- and intraoperative imaging procedure?
Intervention
Diagnostics

5. Concept: hybrid imaging agents
Optical guidance
during surgery
Preoperative
imaging
(often metal-based)
Synthetic incorporation of different imaging features in a single molecule may satisfy a clinical
need for better guidance

6. Imaging modalities: Sensitivity and resolution
PET
SPECT
Fluorescence
MRI
CT
E-15 mol
E-12 mol
E-9 mol
E-6 mol
E-3 mol
E-3mm E-2 mm E-1 mm 1 mm E+1 mm
Sensitivity
Resolution
Most suitable for
molecular imaging
purposes

7. Show clinical potential of multimodal approach
Focus on existing clinical procedure
Sentinel node procedure

8. Multimodal/hybrid tracer for sentinel node biopsy
nanocolloid 99mTc 99mTc-nanocolloid
ICG ICG-99mTc-nanocolloid
“standard” in Europe
Hybrid tracer
In the Netherlands available via GE Healthcare
Buckle et al., Nanotechnology 2011; Brouwer et al., Ann Surg Oncol 2012; Van der Poel et al., Eur Urol 2011; Brouwer et al., J Nucl Med 2012; van den
Berg et al., Eur J Nucl Med Mol Imaging 2012; Mathéron et al., Gynecol Oncol 2013; Schaafsma et al., Br J Surg 2013; Brouwer et al., Eur Urol 2014,
KleinJan et al., Eur Urol 2014; van den Berg et al., Accepted for publication in Radiology 2014

9. Hybrid tracer for combined pre- and intraoperative sentinel node
identification
TOTAL Gamma imaging
BODY
<1CM

10. In prostate cancer patients, lymph node status is an important factor
for the determination of treatment follow-up
Van der Poel et al., Eur Urol 2011; KleinJan et al., Eur Urol 2014

11. Sentinel node biopsy: Identify primary tumor-draining lymph nodes 
stage regional lymphatic system in a minimally invasive way

12. Sentinel node biopsy: Identify primary tumor-draining lymph nodes 
stage regional lymphatic system in a minimally invasive way

13. Sentinel node biopsy: Identify primary tumor-draining lymph nodes 
stage regional lymphatic system in a minimally invasive way

14. SPECT-CT imaging allows anatomical localization of the sentinel nodes
SPECT-CT
3D anatomical roadmap
Lymphoscintigram
Van der Poel et al., Eur Urol 2011; KleinJan et al., Eur Urol 2014

15. Translate acquired imaging information to the operating theatre
Surgery
“ Nurse, get on the internet, go to SURGERY.COM,
scroll down and click on the “Are you totally lost?’
icon.”

16. Henk van der Poel

17. Translating imaging information to the operating theatre

18. Laparoscopic fluorescence camera
lex
Fluorescence
lem
KARL STORZ Endoskopes GmbH & Co. KG Van der Poel et al., Eur Urol 2011; KleinJan et al., Eur Urol 2014

19. Generating fluorescence upon light excitation
1
0.8
0.6
0.4
0.2
0
600 650 700 750 800 850 900
Normalized absorption/emission
Wavelength (nm)
ICG
ICG
lem lex
light

20. Tissue can prohibit effective excitation and emission of the near-infrared
Excitation Emission
Reflection
scattering
2D
scattering
3D
Autofluorescence
dye ICG
lem lex
Light penetration in tissue is wavelength dependent; near-infared light gives superior
penetration
Ambient light

21. Strengths and weaknesses of fluorescence
Positive
- Real-time visual guidance
- High spatial resolution
Negative
- Severe signal attenuation
- No preoperative imaging
Van der Poel et al., Eur Urol 2011; KleinJan et al., Eur Urol 2014

22. Zooming in on individual nodes using fluorescence

23. Real-time fluorescence guidance during sentinel node resection
KARL STORZ Endoskopes GmbH & Co. KG Van der Poel et al., Eur Urol 2011; KleinJan et al., Eur Urol 2014

24. ERUS 2014 conference
Urologists from across Europe
Introduction of fluorescence-guided
sentinel node biopsy to a broad
audience (>800 participants)

25. Next step: Use virtual navigation technologies to guide the placement
of fluorescence cameras

26. Interventional Molecular Imaging Laboratory
Nynke van den Berg
Tessa Buckle (PhD)
Harmen Kloosterboer
Mick Welling (PhD)
Simone van Dijk (MD)
Silvia Spa
Anton Bunschoten (PhD)
Mark Rood
Danny van Willigen
Aldrik Velders (PhD)
Jan-Bart ten Hove
Steffen van der Wal
Fijs van Leeuwen (PhD)
Daphne Rietbergen (MD)
Gijs KleinJan (MD)
Renato Valdés Olmos (MD, PhD)
Frits Smit (MD)
Oscar Brouwer (MD, PhD)
Shaun Xavier (MD)
Matthias van Oosterom
Paulo Waelkens
Thijs Engelen
Julian Sprung
www.imageguidedsurgery.nl