title: Cerenkov luminescence imaging of αv β6 integrin expressing tumors using (90) Y-labeled peptides.
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, (90) Y-DOTA-PEG28 -A20FMDV2 ((90) Y-1) and (90) Y-DOTA-Ahx-A20FMDV2 ((90) Y-2) (>99% radiochemical purity, 3.7 GBq/µmol specific activity) for noninvasive assessment of tumors expressing the integrin αv β6 and their future use in tumor targeted radiotherapy. Cell binding and internalization in αv β6 -positive cells was (90) Y-1: 10.1 ± 0.8%, 50.3 ± 2.1%; (90) Y-2: 22.4 ± 1.7%, 44.7 ± 1.5% with <5% binding to αv β6 -negative control cells. Biodistribution studies showed maximum αv β6 -positive tumor uptake of the radiotracers at 1-h post injection (p.i.) ((90) Y-1: 0.64 ± 0.15% ID/g; (90) Y-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 αv β6 -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.
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, CA, 95616, USA; Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Drishty
authors.initials: D
authors.lastname: Satpati
authors.forename: Sven H
authors.initials: SH
authors.lastname: Hausner
authors.forename: Nadine
authors.initials: N
authors.lastname: Bauer
authors.forename: Julie L
authors.initials: JL
authors.lastname: Sutcliffe
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D049449:Luminescence; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011485:Protein Binding; D011859:Radiography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014759:Viral Envelope Proteins / Q000138:chemical synthesis / Q000502:physiology; D015021:Yttrium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000951:Antigens, Neoplasm; D016023:Integrins; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D014759:Viral Envelope Proteins; D015021:Yttrium Radioisotopes; C073878:integrin alphavbeta6
keywords: A20FMDV2; Cerenkov luminescence imaging; peptide; yttrium 90; αvβ6 integrin