Cerenkov luminescence endoscopy (CLE) is an optical technique that captures the Cerenkov photons emitted from highly energetic moving charged particles (β1 or β−) and can be used to monitor the distribution of many clinically available radioactive probes. A main limitation of CLE is its limited sensitivity to small concentrations of radiotracer, especially when used with a light guide. We investi-gated the improvement in the sensitivity of CLE brought about by using a β − radiotracer that improved Cerenkov signal due to both higher β-particle energy and lower γ noise in the imaging optics because of the lack of positron annihilation. Methods: The signal-to-noise ratio (SNR) of 90Y was compared with that of 18F in both phantoms and small-animal tumor models. Sensitivity and noise characteristics were demonstrated using vials of activity both at the surface and beneath 1 cm of tissue. Rodent U87MG glioma xenograft models were imaged with radiotracers bound to arginine-glycine-aspartate (RGD) peptides to determine the SNR. Results: γ noise from 18F was demonstrated by both an observed blurring across the field of view and a more pronounced fall-off with distance. A decreased γ background and increased energy of the β particles resulted in a 207-fold improvement in the sensitivity of 90Y compared with 18F in phantoms. 90Y-bound RGD peptide produced a higher tumor-to-background SNR than 18F in a mouse model. Conclusion: The use of 90Y for Cerenkov endoscopic imaging enabled superior results compared with an 18F radiotracer
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