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S543
ESTRO 36 2017
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Purpose or Objective
External beam radiotherapy (EBRT) treats gross tumors
and local microscopic diseases. Radionuclide therapy by
isotopes can control tumors systemically. Rhenium 188
(
188
Re)-liposome, a nanoparticle undergoing clinical trials,
emits gamma rays for imaging validation and beta rays for
therapy with biodistribution profiles preferential to
tumors. We designed a unique combinatory treatment and
examined its effects on lung metastasis from esophageal
cancer, a malignancy with poor prognosis.
Material and Methods
Human esophageal cancer BE-3 cells with luciferase gene
for optical imaging were injected into tail vein of nude
mice to induce lung metastasis. The radiochemical purity
of
188
Re-liposome exceeded 95%. Molecular imaging by
NanoSPECT/CT
(NanoSPECT/CT
PLUS,
Mediso,
Alsotorokvesz, Budapest, Hungary) showed that lung
metastatic lesion could uptake the
188
Re-liposome. For
biodistribution, the radioactivity of
188
Re-liposome was
detected by Auto-Gamma counter (Packard Cobra II,
Canberra, Germany), and the uptake of
188
Re-liposome in
each organ was expressed as the percentage of injected
dose per gram of tissue (% ID/g). Low-dose whole lung
EBRT with 3 consecutive daily fractions of 1 Gy was
delivered by linear accelerator with 6-MV photon (Clinac
iX, Varian Medical Systems, USA) followed by intravenous
188
Re-liposome (250 µCi) administration 2-h after last
teletherapy. Flow cytometry was used to estimate the
amount of myeloid derived suppressor cells and
macrophages.
Results
The combination of EBRT and
188
Re-liposome inhibited
tumor burden of lung metastasis faster and better than
each treatment alone (Figure 1 and 2). Combination
treatment did no cause additive adverse effects on white
blood cell counts, body weight, or liver and renal
functions. EBRT significantly reduced the uptake of
188
Re-
liposome in lung, kidney, bone marrow and blood. In
spleen,
188
Re-liposome administration declined the
amount of myeloid derived suppressor cells and increased
the amount of M1 and M2 macrophages.
Figure 1.
The therapeutic efficacy of
188
Re-liposome
combined with EBRT on lung metastasis from esophageal
cancer. The representative optical images show lung
metastatic burden detected by D-luciferin assay.
Figure 2.
The therapeutic efficacy of
188
Re-liposome
combined with EBRT on lung metastasis from esophageal
cancer. Low-dose whole lung EBRT with 3 consecutive
daily fractions of 1 Gy was delivered followed by
intravenous
188
Re-liposome (250 µCi) administration in
combination group. N=3 for each group.
Conclusion
The combination of low-dose whole lung EBRT with
systemic
188
Re-liposome administration might be a
potential treatment modality for lung metastasis from
esophageal
cancer.
Modulation
of
tumor
microenvironment by the combination treatment is
warranted in translational research. This proof-of-concept
study needs to be validated by clinical investigation.
PO-0993 Influence of radiotherapy on differentiation,
maturation and functionality of dendritic cells
L. König
1
, A. Gardyan
2
, J. Hörner-Rieber
1
, P. Huber
2
, K.
Herfarth
1
, S. Rieken
1
1
University Hospital Heidelberg, Department of
Radiation Oncology, Heidelberg, Germany
2
German Cancer Research Center- Heidelberg, Clinical
Cooperation Unit Molecular Radiooncology-, Heidelberg,
Germany
Purpose or Objective
Primary purpose of radiotherapy (RT) is elimination of
cancer cells by inducing DNA-damage that either causes
induction of tumor cell death or inhibition of the
proliferating capacity of these cells. In addition,
considerable evidence emerges that antineoplastic effects
extend beyond these mechanisms. These secondary
effects can contribute to anti-tumor responses in a local
but also systemic manner via activation of the immune
system: The role of dendritic cells (DCs) is well described
to be essential for priming effective radiation-induced
adaptive immunity. Through increased release of tumor-
associated antigens (TAA) after RT, DCs are recruited and
cross-presentation of TAA leads to activation of B- and T-
lymphocytes, therefore playing a pivotal role in adaptive
immune response and immunogenic cell death. However,
there are still many hypotheses regarding the influence of
RT on activation of the immune system. The aim of our
experiments is to further characterize the impact of
different radiation types and dosages on differentiation
and functionality of DCs.
Material and Methods
Human CD14-positive monocytes were isolated from
peripheral blood mononuclear cell samples of six
individuals. In the presence of appropriate cytokine
stimulation with Interleukin-4 (IL-4) and granulocyte
macrophage
colony-stimulating
factor
(GM-CSF)
monocytes were induced into immature DCs (iDCs) and
later mature DCs (mDCs). Monocytes were irradiated with
different photon radiation doses (1x15Gy, 5x2Gy,
1x0.5Gy) on day 0. Maturation to mDCs was induced on day
7 by adding tumor necrosis factor alpha (TNFα) to the
culture medium. Differentiation and maturation of DCs
was assessed on day 2, 9 and 12 by staining of the cell