Cancer Research - Europa

BioCare
Molecular Imaging for Biologically
Optimised Cancer Therapy
Summary
Early tumour detection and response monitoring require
maximum sensitivity and specifi city of the imaging method.
This project focuses on the clinical evaluation and development
of new, more specifi c molecular tracers for the early
detection of tumour cells. A large number of new and
potentially more specifi c tracers than fl uorodeoxy-glucose
(FDG) will be tested, including amino acid analogues, small
tumour-binding peptides, aptamers, peptides binding to
mutant p53 proteins and nanoparticles. The more tumour
specifi c the tracer, the more accurately it will be possible to
image the true tumour cell density and, more importantly,
the true response of the tumour to therapy.
There is also a need to consolidate experience in the use of
recently developed molecular tracers to assess radiotherapy
and chemotherapy response in order to improve on
state-of-the-art treatments. To maximise the sensitivity and
tumour image quality, a high-resolution, wide fi eld-of-view,
ultra-sensitive fully integrated PET-CT camera, capable of
imaging half the human body in a few minutes, will be
designed. Furthermore new adaptive therapy planning and
biological optimisation codes and a dedicated PET-CT
detector for incorporation in treatment units will be designed
in close corporation with university researchers and SMEs.
This will allow an effi cient clinical integration and high
patient throughput. The associated increase in accuracy of
tumour imaging and the three-dimensional in vivo tumour
responsiveness data will hopefully allow the clinical introduction
of accurate biologically based adaptive treatment
optimisation methods.
Problem
Keywords | Molecular tumour imaging | cancer therapy | PET-based treatment planning | PET-CT simulation |
apoptosis | tumour hypoxia | aptamers | PET-CT-RT | diagnostic treatment unit |
Cancer imaging is at the dawn of a third revolution of accurate
tumour diagnostics. During the 1970s and early 1980s,
computed tomography (CT) with diagnostic X-rays made
a revolution in accurate delineation of normal tissue anatomy
as well as gross tumour growth. In the mid 1980s and
1990s, magnetic resonance imaging and spectroscopy (1.2)
allowed even more accurate diff erential diagnostics of soft
tissue malignancies with the possibility of distinguishing
between tumour tissues, oedema and normal tissues. The integration
of positron emission and X-ray computed tomography
in one unit and MRSI – MR spectroscopic imaging – is bringing
a third diagnostic revolution to tumour imaging. By combining
these two imaging modalities, an unprecedented accuracy in
the delineation of the tumour on a background of normal
tissue anatomy is achieved.
Obviously, fl uorodeoxyglucose (FDG) is not tumour-specifi c,
as all regions with an increased metabolic rate will show an
elevated uptake. However, in the new era of molecular imaging
it is likely to be followed by more specifi c tumour
markers, allowing an even more accurate imaging of the
tumour clonogen density. Methionine and other amino acids
are already available as tracers and, although they may be
better than FDG, they may still not be suffi ciently specifi c,
since they are incorporated in all tissues that are being
renewed. For some tumours, there are more specifi c markers
such as 11 C-Choline, and FHBC or FDHT (fl uorodihydrotestosterone)
for imaging androgen receptors in prostate
cancer. Vasculature could be visualisable by known tracers
such as ammonia ( 11 CH 3 ) or water (H 2 15 O).
Aim
Molecular imaging of radiation-induced alteration of tumour
cell proliferation and functional receptor expression. In
recent years, radiotracer-based molecular imaging with
positron emission tomography in oncology has evolved as a
valuable tool for staging of disease and evaluation of therapy
response. This success is mainly based on the application
of the glucose analogue 18Fluorodeoxyglucose, which traces
tumour tissue by the fact that most tumours exhibit
enhanced glucose consumption. But the tumour microenvironment
is not depending only on glucose metabolism.
Perfusion, hypoxia, amino acid uptake and receptor status
are important parameters which have high impact on the
treatment success. Additionally to ‘the classics’, FDG and
methionine, new PET-tracers to monitor these parameters
are under development. With the advent of high-resolution
animal PET scanners there is now the opportunity to investigate
in vivo the tumour microenvironment of transplanted
tumours in small animals under therapy conditions, especially
for radiation therapy – for example the knowledge on
the course of oxic or hypoxic conditions has the potential to
develop strategies to overcome treatment failure due to
hypoxia-related radiation resistance. PET off ers the opportunity
to investigate the radiation response of tumours
longitudinal during the treatment time, to evaluate the predictive
strength of diff erent parameters or their combination,
and to test the effi cacy of newly developed tracers in comparison
to ‘standard tracers’. The functional PET data will be
supplemented by tumour histology, immunohisto-chemistry
and autoradiography to complement the tumour-pathophysiologic
data.
In the future we thus need improved tracers to the image
tumour spread before treatment. This will enable accurate
delineation of the clinical target volume based on visualised
uptake by the tumour, for example along well-known pathways
of microscopic lymphatic invasion.
108 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME