Abstract
A first-of-its-kind (18)F pretargeted PET imaging approach based on the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) is presented. As proof-of-principle, a TCO-bearing immunoconjugate of the anti-CA19.9 antibody 5B1 and an Al[(18)F]NOTA-labeled tetrazine radioligand were harnessed for the visualization of CA19.9-expressing BxPC3 pancreatic cancer xenografts. Biodistribution and (18)F-PET imaging data clearly demonstrate that this methodology effectively delineates tumor mass with activity concentrations up to 6.4 %ID/g at 4 h after injection of the radioligand.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigens, Tumor-Associated, Carbohydrate / analysis
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Click Chemistry / methods
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Cycloaddition Reaction / methods
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Cyclooctanes / chemistry*
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Cyclooctanes / pharmacokinetics
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Fluorine Radioisotopes / chemistry*
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Fluorine Radioisotopes / pharmacokinetics
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Humans
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Immunoconjugates / chemistry*
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Immunoconjugates / pharmacokinetics
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Mice
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Pancreas / pathology
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Pancreatic Neoplasms / diagnosis*
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Pancreatic Neoplasms / pathology
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Positron-Emission Tomography / methods*
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Radiopharmaceuticals / chemistry
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Radiopharmaceuticals / pharmacokinetics
Substances
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Antigens, Tumor-Associated, Carbohydrate
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Cyclooctanes
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Fluorine Radioisotopes
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Immunoconjugates
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Radiopharmaceuticals
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carbohydrate antigen 199, human