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Cerenkov luminescence imaging of αvβ6 integrin expressing tumors using 90Y‐labeled peptides
Authors:Drishty Satpati  Sven H. Hausner  Nadine Bauer  Julie L. Sutcliffe
Affiliation:1. Department of Biomedical Engineering, University of California Davis, Davis, CA, USA;2. Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, Sacramento, USA;3. Center for Molecular and Genomic Imaging, University of California, Davis, CA, USA
Abstract:Cerenkov luminescence imaging (CLI) is an emerging preclinical molecular imaging modality that tracks the radiation emitted in the visible spectrum by fast moving charged decay products of radionuclides. The aim of this study was in vitro and in vivo evaluation of the two radiotracers, 90Y‐DOTA‐PEG28‐A20FMDV2 (90Y‐1) and 90Y‐DOTA‐Ahx‐A20FMDV2 (90Y‐2) (>99% radiochemical purity, 3.7 GBq/µmol specific activity) for noninvasive assessment of tumors expressing the integrin αvβ6 and their future use in tumor targeted radiotherapy. Cell binding and internalization in αvβ6‐positive cells was 90Y‐1: 10.1 ± 0.8%, 50.3 ± 2.1%; 90Y‐2: 22.4 ± 1.7%, 44.7 ± 1.5% with <5% binding to αvβ6‐negative control cells. Biodistribution studies showed maximum αvβ6‐positive tumor uptake of the radiotracers at 1‐h post injection (p.i.) (90Y‐1: 0.64 ± 0.15% ID/g; 90Y‐2: 0.34 ± 0.11% ID/g) with high renal uptake (>25% ID/g at 24 h). Because of the lower tumor uptake and high radioactivity accumulation in kidneys (that could not be reduced by pre‐administration of either lysine or furosemide), the luminescence signal from the αvβ6‐positive tumor was not clearly detectable in CLI images. The studies suggest that CLI is useful for indicating major organ uptake for both radiotracers; however, it reaches its limitation when there is low signal‐to‐noise ratio.
Keywords:Cerenkov luminescence imaging  yttrium 90  α    6 integrin  A20FMDV2  peptide
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