ESTRO 38 Abstract book

S291 ESTRO 38

complex genotype data and approaches that combine biological knowledge with genotype data.

indicative of a reduction in T-cell infiltration. These results suggest that tumor irradiation and vaccination increase the influx of activated T-cells and that CXCR4 receptor-mediated signaling is involved in the migration and infiltration of these T-cells. Taken together, this study demonstrates the potential of PET imaging for non-invasively monitoring of the immune response to anti-cancer treatments, like immunotherapy and radiotherapy. Currently, the first clinical studies evaluating the feasibility of [ 18 F]FB-IL2 PET to detect the immune response in tumor lesions during immunotherapy and chemo-radiotherapy are in progress. 1 Oxford Cancer Center - Churchill Hospital Oxford inst for RO, Radiopharmaceuticals and Molecular Imaging Group, Oxford, United Kingdom Abstract text DNA integrity is continuously challenged by endogenous and exogenous factors that can damage or alter the DNA sequence, leading to mutagenesis, aberrant transcriptional activity, and cytotoxicity. Left unrepaired, damaged DNA can ultimately lead to the development of cancer. To overcome this threat, a series of complex mechanisms collectively known as the DNA damage response (DDR) are able to detect the various types of DNA damage that can occur and stimulate the appropriate repair process. Each DNA damage repair pathway leads to the recruitment, upregulation, or activation of specific proteins within the nucleus, which, in some cases, represent attractive targets for molecular imaging. Given the dominant involvement of DNA damage and its repair during radiotherapy, the ability to monitor these repair processes non-invasively using nuclear imaging techniques may facilitate monitoring response to DNA damaging treatments. The aim of this talk is to provide an overview of recent efforts to develop PET and SPECT radiotracers for imaging of DNA damage repair proteins. SP-0555 MRI-CEST Imaging of tumor acidosis D. Longo 1 1 Italian National Research Council (CNR) Institute of Biostructures and Bioimaging (IBB) Abstract text Up-regulated glucose metabolism, upon hypoxia-induced shift toward glycolysis, leads to enhanced acidification of the extracellular pH (pHe) to values in the range 6.5-7.0, which is a salient feature of the tumor microenvironment. Consequently, tumor cells have evolved several sophisticated mechanisms to regulate pH homeostasis: they eliminate acidic catabolites by ion transporters and pumps to preserve a slightly alkaline intracellular pH (pHi), which is optimal for cell proliferation and tumor survival. Imaging based methods are already been established, at a clinical level, to assess glucose metabolism (by positron emission tomography - PET imaging of 18F-fluorodeoyglucose FDG tumor uptake) providing a formidable tool for evaluating treatment response. Conversely, despite the excellent studies regarding tumor acidosis, we still do not have an effective imaging protocol that allow to quantify extracellular tumor pH and to assess pHe related changes following therapeutic treatment. Furthermore, new anticancer drugs that, upon inhibiting one or more of these pH regulators causing both the pHi and the pHe values to return to normal, with the consequent impairment of tumour growth, cannot be in vivo evaluated both at preclinical and clinical level. We have developed innovative MRI-based approaches for assessing in vivo tumor acidosis by exploiting already clinically-used x-ray contrast agents that are translatable to the clinical scenario. We have exploited tumor pH SP-0554 Imaging DNA damage response B. Cornelissen 1

Symposium: Biological Imaging for Radiotherapy

SP-0553 Imaging of tumor infiltrating lymphocytes with [18F]FB-IL2 PET E. De Vries 1 , S. Hartimath 1 , O. Draghiciu 2 , V. Manuelli 1 , A. Van Waarde 1 , R. Dierckx 1 , T. Daemen 2 , H. Nijman 3 1 University of Groningen- University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Groningen, The Netherlands; 2 University of Groningen- University Medical Center Groningen, Medical Microbiology- Tumor Virology and Cancer Immunotherapy, Groningen, The Netherlands ; 3 University of Groningen- University Medical Center Groningen, Gynecological Oncology, Groningen, The Netherlands Abstract text Cytotoxic T-cells play an important role in the response to cancer treatment. T-cells can be (re)activated by e.g. immunotherapy, chemotherapy or radiotherapy and subsequently contribute to the destruction of the tumor. Insight in the immune response in the tumor can facilitate optimal treatment with minimal side effects. Non-invasive imaging of infiltrating activated T-cells would be very useful for monitoring the immune response within the tumor. Positron Emission Tomography (PET) could be such a tool, provided that a suitable tracer is available. Therefore, we have developed the PET tracer, [ 18 F]FB-IL2, that binds specifically to interleukin-2 (IL2) receptors, that are predominantly expressed by activated T-cells. Since chemokine receptors direct the migration of T-cells to the tumor, we have also developed the PET tracer N- [ 11 C]methyl-AMD3465 for imaging of CXCR4 receptors on T cells. The imaging properties of both tracers were successfully evaluated in several rodent models. To demonstrate the feasibility of the imaging methods to monitor the immune response to treatment, PET imaging with [ 18 F]FB-IL2 and N-[ 11 C]methyl-AMD3465 was performed in TC-1 tumor-bearing mice. Mice were treated with sham-irradiation (control), with a single 14Gy dose of tumor irradiation alone, or with tumor irradiation in combination with vaccination against human papilloma virus antigens that are expressed by the tumor cells. To investigate whether infiltration of lymphocytes is mediated by the CXCR4 receptor signaling pathway, a group of animals were treated with radiotherapy in combination with the CXCR4 antagonist Plerixafor (AMD3100). PET imaging of IL2 receptors on activated T-cells 4 days after (sham-)irradiation showed a 10-fold increase in [ 18 F]FB-IL2 uptake in the tumor of mice treated with radiotherapy alone, when compared to controls. When radiotherapy was combined with vaccination, the tumor uptake of [ 18 F]FB-IL2 was even further increased by another 2.7-fold. These results were in line with flow cytometry data of CD8+ T-cells in the tumor. Interestingly, the combination of radiotherapy and vaccination – but not tumor irradiation alone – significantly increased the [ 18 F]FB-IL2 uptake in various organs, indicating that the immune response to tumor irradiation is restricted to the tumor, whereas the addition of vaccination induced a more widely spread immune response. PET imaging of CXCR4 receptor expression showed similar results as [ 18 F]FB-IL2 PET, with N-[ 11 C]methyl-AMD3465 uptake being increased 2.5- and 4-fold in mice treated with radiotherapy alone, or radiotherapy in combination with vaccination, respectively. Moreover, [ 18 F]FB-IL2 PET showed that blocking of the CXCR4-mediated signaling pathway with the antagonist Plerixafor, resulted in a 2.8- fold reduction tracer uptake in the irradiated tumor,