5th EuropEan MolEcular IMagIng MEEtIng - ESMI

5th EuropEan MolEcular IMagIng MEEtIng – EMIM2010
Real time per operative optical imaging for the improvement of tumour surgery in an in vivo
micro-metastases model
Keramidas M. , Josserand V. , Righini C. , Coll J. L.
INSERM U823, Grenoble, France
michelle.keramidas@ujf-grenoble.fr
Introduction: In a wide range of cancer cases,
surgery is the first therapeutic indication before
radiotherapy and chemotherapy. In that
way the prognostic strongly depends on the tumour
removal exhaustiveness and in particular
on metastases elimination.
We developed a couple near-infrared fluorescent
tracer / per operative detection system in
order to improve tumour surgery efficacy.
RAFT-c(RGD)4-Alexa 700 (Angiostamp®, Fluoptics)
specifically bind to integrin αvß3, a
receptor strongly expressed in angiogenesis
and in many tumour types. The per-operative
detection system (Fluobeam 700, Fluoptics) is
a portative 2D fluorescent imager that can be
used in white light environment and so, could
be used directly during surgery to help the surgeon
for tumour and metastases excision.
We already demonstrated in animal models
the very significant improvement in primary
tumours resection: higher number of tumour
nodules removed, sane margins on the removed
fragments and surgery time divided by 2 (Keramidas
M., British Journal of Surgery 2010).
In the clinical situation, recurrence of cancer
by metastases invasion after primary tumour
surgery is a critical point. The aim of the present
study is to evaluate the metastases resection
impact on the survey. In order to proceed we
first need to establish a suitable animal model
of micro-metastases following primary tumour
surgery. After calibration of the metastatic
in vivo model, we will evaluate the survey of
the twice-operated animals (metastases resection
after primary tumour removal) versus the
once-operated animals (only primary tumour
removal).
Methods: Luciferase positive tumour cells (TS/
Apc-luc) are injected in the kidney capsule of
nude mice and the primary tumour growth is
followed by in vivo bioluminescence imaging.
7 days after tumour cells implantation, the tumoral
kidney is removed and the metastases
development is followed by in vivo bioluminescence
imaging. Then RAFT-c(RGD)4-Alexa
700 is injected intravenously and twenty-four
hours later the portative fluorescence detection
system is used to assist the metastases excision.
The possible recurrence of cancer is followed
by in vivo bioluminescence imaging. Mice are
sacrificed when they loose 10% of their weight.
The mice survey is compared with the one of
two control groups: in one group the mice don’t
undergo the second surgery for metastases resection,
and in a second group the mice don’t
undergo any surgery and keep the primary kidney
tumour.
Results: Micro-metastases appear about 7 days
after the primary tumour removal and soar up
to 20 days after the first surgery. The metastases
removal assisted by the RAFT-c(RGD)4-Alexa
700 and the per operative fluorescence detection
system significantly improved the mice
survey (36 days).
Conclusions: We developed an in vivo model of
micro-metastases invasion following primary
tumour surgery which is very relevant regarding
to the clinical situation of head and neck
or prostate cancer. The use of RAFT-c(RGD)4-
Alexa 700 coupled with the portative device allows
micro-metastases detection, significantly
improve their resection and increase the mice
survey.
References:
1. Intraoperative near-infrared image guided surgery for
peritoneal carcinomatosis in a preclinical experimental
model. M. KERAMDAS, V. JOSSERAND, RIGHINI C.A., WENK
C., FAURE C. And COLL J.L. British Journal of Surgery,2010.
EuropEan SocIEty for MolEcular IMagIng – ESMI
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