Improved stability of a novel fluorine-18 labeled TCO analogue for pretargeted PET imaging

Ruivo, Eduardo; Adhikari, Karuna; Elvas, Filipe; Fissers, Jens; Vangestel, Christel; Staelens, Steven; Stroobants, Sigrid; Veken, Pieter Van der; wyffels, Leonie; Augustyns, Koen

doi:10.1016/j.nucmedbio.2019.11.001

Cited by 16 publications

(25 citation statements)

References 18 publications

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“…Compounds with both TCO and Tz moieties, especially Tz, are known to accumulate in hepatobiliary organs (38,39). For this reason, one of our design considerations was to strategically position the RBBE-cleavable linker in such a way that likely radiolabeled catabolites would be devoid of Tz and TCO moieties.…”

Section: Discussionmentioning

confidence: 99%

Site-Specific and Residualizing Linker for ¹⁸F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment

et al. 2021

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Single domain antibody fragments (sdAbs) are promising vectors for immunoPET; however, better methods for labeling sdAbs with 18 F are needed. Herein, we evaluate a site-specific strategy utilizing an 18 F residualizing motif and the anti-HER2 sdAb 5F7 bearing an engineered C-terminal GGC tail. Methods: 5F7GGC was site-specifically attached with a tetrazine-bearing agent via thiol-maleimide reaction. The resultant conjugate was labeled with 18 F by inverse electron demand Diels-Alder cycloaddition with a trans-cyclooctene attached to 6-18 Ffluoronicotinoyl moiety via a renal brush border enzyme-cleavable linker and a PEG 4 chain ( 18 F-5F7GGC). For comparisons, 5F7 sdAb was labeled using the prototypical residualizing agent, Nsuccinimidyl 3-(guanidinomethyl)-5-125 I-iodobenzoate (iso-125 I-SGMIB). The two labeled sdAbs were compared in paired-label studies performed in the HER2-expressing BT474M1 breast carcinoma cell line and athymic mice bearing BT474M1 subcutaneous xenografts. MicroPET/CT imaging after administration of 18 F-5F7GGC in the above mouse model was also carried out.Results: 18 F-5F7GGC was synthesized in an overall radiochemical yield of 8.9 ± 3.2% with retention of HER2 binding affinity and immunoreactivity. The total cell-associated and intracellular activity for 18 F-5F7GGC was similar to that for co-incubated iso-125 I-SGMIB-5F7. Likewise, the uptake of 18 F-5F7GGC in BT474M1 xenografts in mice was similar to that for iso-125 I-SGMIB-5F7; however, 18 F-5F7GGC exhibited significantly more rapid clearance from the kidney.MicroPET/CT imaging confirmed high uptake and retention in the tumor with very little background activity at 3 h except in the bladder. Conclusion: This site-specific and residualizing 18 F labeling strategy could facilitate clinical translation of 5F7 anti-HER2 sdAb as well as other sdAbs for immunoPET.

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Section: Discussionmentioning

confidence: 99%

Site-Specific and Residualizing Linker for ¹⁸F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment

et al. 2021

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“…However, the long biological half-life of mAbs calls for labeling with long-lived radionuclides to warrant sufficient accumulation of radioactivity at the tumor sites. This approach is unfortunately limited by the long circulation of the radiolabeled molecule in the blood and the radiotoxicity induced to nontargeted organs [ 86 ]. To overcome this limitation, Ruivo and coworkers made use of the pretargeting method to combine the specificity of mAbs with the fast pharmacokinetics of radiolabeled small molecules.…”

Section: Applicationsmentioning

confidence: 99%

“…Ex vivo biodistribution revealed increase tumor uptake overtime, which was confirmed by PET imaging data. Several other 18 F-labeled tetrazines have been developed due to the attractive decay properties ( t 1/2 = 109.8 min) of fluorine-18 for PET imaging [ 86 ]. Keinänen et al described a method for the preparation of a 18 F-labeled glycosylated tetrazine by oxime ligation between 5-[ 18 F]fluoro-5-deoxyribose and an aminooxy functionalized tetrazine [ 89 ].…”

Section: Applicationsmentioning

confidence: 99%

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IEDDA: An Attractive Bioorthogonal Reaction for Biomedical Applications

2021

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The pretargeting strategy has recently emerged in order to overcome the limitations of direct targeting, mainly in the field of radioimmunotherapy (RIT). This strategy is directly dependent on chemical reactions, namely bioorthogonal reactions, which have been developed for their ability to occur under physiological conditions. The Staudinger ligation, the copper catalyzed azide-alkyne cycloaddition (CuAAC) and the strain-promoted [3 + 2] azide–alkyne cycloaddition (SPAAC) were the first bioorthogonal reactions introduced in the literature. However, due to their incomplete biocompatibility and slow kinetics, the inverse-electron demand Diels-Alder (IEDDA) reaction was advanced in 2008 by Blackman et al. as an optimal bioorthogonal reaction. The IEDDA is the fastest bioorthogonal reaction known so far. Its biocompatibility and ideal kinetics are very appealing for pretargeting applications. The use of a trans-cyclooctene (TCO) and a tetrazine (Tz) in the reaction encouraged researchers to study them deeply. It was found that both reagents are sensitive to acidic or basic conditions. Furthermore, TCO is photosensitive and can be isomerized to its cis-conformation via a radical catalyzed reaction. Unfortunately, the cis-conformer is significantly less reactive toward tetrazine than the trans-conformation. Therefore, extensive research has been carried out to optimize both click reagents and to employ the IEDDA bioorthogonal reaction in biomedical applications.

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The inverse electron demand Diels–Alder cycloaddition with carbon‐11 and fluorine‐18: A gateway to pretargeted imaging across the blood–brain barrier

Zientek

Thompson

Sephton

et al. 2023

Labelled Comp Radiopharmac

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Improved stability of a novel fluorine-18 labeled TCO analogue for pretargeted PET imaging

Cited by 16 publications

References 18 publications

Site-Specific and Residualizing Linker for ¹⁸F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment

Site-Specific and Residualizing Linker for ¹⁸F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment

IEDDA: An Attractive Bioorthogonal Reaction for Biomedical Applications

The inverse electron demand Diels–Alder cycloaddition with carbon‐11 and fluorine‐18: A gateway to pretargeted imaging across the blood–brain barrier

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Improved stability of a novel fluorine-18 labeled TCO analogue for pretargeted PET imaging

Cited by 16 publications

References 18 publications

Site-Specific and Residualizing Linker for 18F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment

Site-Specific and Residualizing Linker for 18F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment

IEDDA: An Attractive Bioorthogonal Reaction for Biomedical Applications

The inverse electron demand Diels–Alder cycloaddition with carbon‐11 and fluorine‐18: A gateway to pretargeted imaging across the blood–brain barrier

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Product

Resources

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Site-Specific and Residualizing Linker for ¹⁸F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment

Site-Specific and Residualizing Linker for ¹⁸F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment