Autoradiography potentially offers high molecular sensitivity and spatial resolution for tumor margin estimation. However, conventional autoradiography requires sectioning the sample which is destructive and labor-intensive. Here we describe a novel autoradiography technique that uses a flexible ultra-thin scintillator which conforms to the sample surface. Imaging with the flexible scintillator enables direct, high-resolution and high-sensitivity imaging of beta particle emissions from targeted radiotracers. The technique has the potential to identify positive tumor margins in fresh unsectioned samples during surgery, eliminating the processing time demands of conventional autoradiography. We demonstrate the feasibility of the flexible autoradiography approach to directly image the beta emissions from radiopharmaceuticals using lab experiments and GEANT-4 simulations to determine i) the specificity for 18F compared to 99mTc-labeled tracers ii) the sensitivity to detect signal from various depths within the tissue. We found that an image resolution of 1.5 mm was achievable with a scattering background and we estimate a minimum detectable activity concentration of 0.9 kBq/ml for 18F. We show that the flexible autoradiography approach has high potential as a technique for molecular imaging of tumor margins using 18F-FDG in a tumor xenograft mouse model imaged with a radiation-shielded EMCCD camera. Due to the advantage of conforming to the specimen, the flexible scintillator showed significantly better image quality in terms of tumor signal to whole-body background noise compared to rigid and optimally thick CaF2:Eu and BC400. The sensitivity of the technique means it is suitable for clinical translation.
K. N. Vyas, M. Grootendorst, T. Mertzanidou, S. Macholl, D. Stoyanov, S. R. Arridge, and D. S. Tuch, "Flexible scintillator autoradiography for tumor margin inspection using 18F-FDG," Proc. SPIE 10478, Molecular-Guided Surgery: Molecules, Devices, and Applications IV, 1047811 (Presented at SPIE BiOS: January 29, 2018; Published: 1 March 2018); https://doi.org/10.1117/12.2289693.
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