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(18)F-Based Pretargeted PET Imaging Based on Bioorthogonal Diels-Alder Click Chemistry.

Meyer JP, Houghton JL, Kozlowski P, Abdel-Atti D, Reiner T, Pillarsetty NV, Scholz WW, Zeglis BM, Lewis JS - Bioconjug. Chem. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.

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.

No MeSH data available.


Related in: MedlinePlus

Results ofthe biodistribution pretargeting CA19.9 with [18F]2/5B1-TCO. Subcutaneous BxPC3 xenograft bearing micewere administered 5B1-TCO (1.33 nmol) 72 h prior to the injectionof the 18F-labeled tracer (1.33 nmol, 1.8–2.0 MBq)via the tail vein before the mice were euthanized, and the organscollected at the appropriate time points.
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fig2: Results ofthe biodistribution pretargeting CA19.9 with [18F]2/5B1-TCO. Subcutaneous BxPC3 xenograft bearing micewere administered 5B1-TCO (1.33 nmol) 72 h prior to the injectionof the 18F-labeled tracer (1.33 nmol, 1.8–2.0 MBq)via the tail vein before the mice were euthanized, and the organscollected at the appropriate time points.

Mentions: In subsequent pretargetedbiodistribution experiments, nude, athymicmice bearing subcutaneous CA19.9-expressing BxPC3 xenografts wereinjected with 5B1-TCO (1.33 nmol of 5B1) 72 h prior to the administrationof [18F]2 (1.33 nmol, 1.8–2.0 MBq)(Figure 2).


(18)F-Based Pretargeted PET Imaging Based on Bioorthogonal Diels-Alder Click Chemistry.

Meyer JP, Houghton JL, Kozlowski P, Abdel-Atti D, Reiner T, Pillarsetty NV, Scholz WW, Zeglis BM, Lewis JS - Bioconjug. Chem. (2015)

Results ofthe biodistribution pretargeting CA19.9 with [18F]2/5B1-TCO. Subcutaneous BxPC3 xenograft bearing micewere administered 5B1-TCO (1.33 nmol) 72 h prior to the injectionof the 18F-labeled tracer (1.33 nmol, 1.8–2.0 MBq)via the tail vein before the mice were euthanized, and the organscollected at the appropriate time points.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4759614&req=5

fig2: Results ofthe biodistribution pretargeting CA19.9 with [18F]2/5B1-TCO. Subcutaneous BxPC3 xenograft bearing micewere administered 5B1-TCO (1.33 nmol) 72 h prior to the injectionof the 18F-labeled tracer (1.33 nmol, 1.8–2.0 MBq)via the tail vein before the mice were euthanized, and the organscollected at the appropriate time points.
Mentions: In subsequent pretargetedbiodistribution experiments, nude, athymicmice bearing subcutaneous CA19.9-expressing BxPC3 xenografts wereinjected with 5B1-TCO (1.33 nmol of 5B1) 72 h prior to the administrationof [18F]2 (1.33 nmol, 1.8–2.0 MBq)(Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.

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.

No MeSH data available.


Related in: MedlinePlus