ESTRO 2023 - Abstract Book

S57

Saturday 13 May

ESTRO 2023

Conclusion The hypoxia related marker CAIX can be used to visualize hypoxic and immunological cold areas in syngeneic mouse models using the SPECT-radiotracer [In111]-DTPA-mCAIX. We show this technique is able to distinguish CAIX high from CAIX low tumors by ex vivo analysis and in vivo SPECT/CT imaging. In the future, this technique could be used to distinguish hypoxic from non-hypoxic tumors before or during hypoxia targeted or reducing treatment and thereby help optimizing this strategy to improve immuno- and radiotherapy efficacy in preclinical models. OC-0094 Radiobiological models for microvascular damage including functional impairment of capillary wall L. Possenti 1 , M. Magnoni 2 , T. Giandini 3 , V. Doldi 4 , S. Bersini 5 , C. Arrigoni 5 , M.L. Costantino 2 , N. Zaffaroni 4 , M. Moretti 5,6 , T. Rancati 1 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Prostate cancer program, Milan, Italy; 2 Politecnico di Milano, LaBS, Chemistry, Materials and Chemical Engineering Dept., Milan, Italy; 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Physics Unit, Milan, Italy; 4 Fondazione IRCCS Istituto Nazionale dei Tumori, Molecular Pharmacology Unit, Department of experimental oncology , Milan, Italy; 5 Ente Ospedaliero Cantonale, Regenerative Medicine Technologies Laboratory, Service of Orthopaedics and Traumatology, Bellinzona, Switzerland; 6 Università della Svizzera Italiana, Faculty of Biomedical Sciences, Lugano, Switzerland Purpose or Objective The microvasculature is essential to the microenvironment, delivering metabolites and clearing tissue from wastes. Ionizing radiations have a detrimental effect on such small vessels, possibly contributing to healthy tissue damage, i.e. toxicity, following radiotherapy. We present an advanced radiobiological model of microvasculature that allows (i) sample irradiation in a controlled 3D environment and (ii) the evaluation of vessel wall permeability. Materials and Methods Microfluidic chips (Figure 1) are produced via soft-lithography with PDMS, then plasma-bonded on a coverslip glass. The microvascular network is generated via pseudo-vasculogenesis in the central region of the chip using GFP-HUVEC (4.5 M/ml), dermal fibroblast (4.5 M/ml), and fibrinogen-thrombin gel (3 mg/ml-4UI/ml). The network is cultured for seven days and then irradiated at 2, 5, 8, and 10 Gy (Figure 1) with 6 MV photons produced by a Varian linear accelerator (dose rate 2.8 Gy/min). An ad-hoc slab phantom was built to simulate surrounding tissues, and the irradiation was planned with the treatment planning systems to deliver the specified doses to the entire chip (Figure 1). Radiation damage was assessed at two different time points (3h and 24 h post-irradiation) by quantifying γ H2AX foci, to evaluate double-strand breaks (DSBs), and wall permeability, monitoring TRITC dextran (MW= 40 kDa) diffusion.