Cerenkov luminescence imaging of αv ß6 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 ß6 and their future use in tumor targeted radiotherapy. Cell binding and internalization in αv ß6 -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 ß6 -negative control cells. Biodistribution studies showed maximum αv ß6 -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 ß6 -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.