18F]FB-IL2 PET combined with multi-parametric MRI to analyze treatment-induced changes in tumor microenvironment in advanced cervical cancer

Currently, treatment options for cervical cancer, more specificly for
metastatic, recurrent and persistent disease, are essentially non-existent.
There is clearly a need for innovative therapies for this disease. In recent
years immunotherapy is gaining its place as single or combined treatment
modality in the field of cancer , however for the use in cervical cancer,
immunotherapy is still in early developmental stages. Immunotherapy is often
accompanied by serious immune-related adverse events and high costs. Selecting
the right patients for this kind of treatment and tailoring their therapy is
therefore crucial. This not only applies to immunotherapy, but also to other
treatment strategies. For this purpose, adequate predictors or early read-outs
are essential, but are currently lacking.
The [18F]FB-IL2 PET scan is developed to detect T cell influx and changes in T
cell status within the tumor which might reflect response to treatment . The
combination with an MRI scan, which is used in the standard diagnostic work-up
of cervix cancer, should provide exact the anatomical location. In addition,
MRI can give information on tumor perfusion and diffusion restriction in the
tumor. Aberrant microvasculature can not only hamper the influx of immune
cells, but also affect the delivery of therapeutic drugs to the tumor. For this
reason, immunotherapies may need to be combined with drugs targeting tumor
angiogenesis. MRI could help in determining whether these drugs are able to
normalize the tumor vasculature and thus increase the potential efficacy of
immunotherapy. This study could aid the clinical validation of [18F]FB-IL2 by
enabling assessment of the impact of perfusion and diffusion on the uptake of
[18F]FB-IL2 in tumor lesions. Since immunotherapies are currently not standard
treatment for cervical cancer, the feasibility of the [18F]FB-IL2 PET scan to
detect tumor infiltrating T cells will be assessed in patients that are being
treated with radiochemotherapy according to the standard of care. Like
immunotherapy, radiochemotherapy is also accompanied by enhanced tumor
infiltration of activated T cells.

To assess the potential of [18F]FB-IL2 PET to detect the infiltration of IL2
receptor (IL2R) positive immune cells in cervical cancer tissue during
radiochemotherapy treatment using IL2 receptor positive cells in tumor biopsies
as (golden standard).

This study is a single-center feasibility (observational) study for the use of
[18F]FB-IL2 PET and multiparametric MRI to monitor changes in CD25+ T cell
influx and changes in microvasculature in tumors of patients with locally
advanced cervical cancer during radiochemotherapy. These changes will be
compared to tumor biopsies (golden standard).

The toxicity profile of IL2 (Proleukin®) in humans and animals is well known.
In fact, the first patients that underwent an [18F]FB-IL2 PET scan did not show
any signs of toxicity. The radiation burden will add up to a total dose of
12.3 mSv. This complies with category III (moderate risk ICRP 62). In
comparison to the radiotherapy dose (80Gy) given to the primary tumor site
during radio chemotherapy this is negligible. In addition to the [18F]FB-IL2
PET IL2 PET a multiparametric MRI will be performed. This will take 45 minutes.
MRI poses no additional radiation burden. Side effects to MRI contrast agents
are extremely rare. The risk of an acute reaction for a gadolinium based
contrast agent is lower than the risk with a iodine-based contrast agent.
Besides imaging, patients will be asked to give 3 blood samples and 3 biopsies
which will be taken at baseline, during and at the end of treatment, if
feasible. Biopsies at baseline and at the end of treatment will be taken during
the examination under general anesthesia which is part of the standard care at
that time point. The biopsy during treatment will be performed without
anesthesia in the outpatient clinic and is optional. We aim to combine all
study procedures with a regular visit to the hospital in order to reduce the
burden of the study. This study will not have a direct benefit for the
participants, but is the first step towards the clinical validation of a new
diagnostic tool that could aid the stratification of patients, thus avoiding
ineffective and expensive treatments that can be accompanied by potentially
life-threatening side effects.