Cerenkov luminescence imaging of αvβ6 integrin expressing tumors using 90Y-labeled peptides

Drishty Satpati, Sven H. Hausner, Nadine Bauer, Julie Sutcliffe

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 αvβ 6-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.

Original languageEnglish (US)
Pages (from-to)558-565
Number of pages8
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume57
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Luminescence
Integrins
Tumors
Imaging techniques
Peptides
Neoplasms
Molecular imaging
Molecular Imaging
Furosemide
Radioactivity
Radiotherapy
Signal-To-Noise Ratio
Radioisotopes
Lysine
Signal to noise ratio
Cells
Radiation
Kidney

Keywords

  • A20FMDV2
  • Cerenkov luminescence imaging
  • peptide
  • yttrium 90

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Drug Discovery
  • Radiology Nuclear Medicine and imaging
  • Biochemistry

Cite this

Cerenkov luminescence imaging of αvβ6 integrin expressing tumors using 90Y-labeled peptides. / Satpati, Drishty; Hausner, Sven H.; Bauer, Nadine; Sutcliffe, Julie.

In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 57, No. 9, 2014, p. 558-565.

Research output: Contribution to journalArticle

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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 αvβ 6-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.",
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