Development of [¹⁸F]AmBF₃ Tetrazine for Radiolabeling of Peptides: Preclinical Evaluation and PET Imaging of [¹⁸F]AmBF₃-PEG₇-Tyr³-Octreotide in an AR42J Pancreatic Carcinoma Model

Recent Advances in Bioorthogonal Click Chemistry for Enhanced PET and SPECT Radiochemistry

“…95 Two Tyr 3 octreotide (TOC)based radiotracers were synthesized using IEDDA between a [ 18 F]F-Tz derivative with a 19 F− 18 F-exchange-generated AmBF 3 moiety and a TCO-modified octreotide precursor with PEG linkers. 96 In this study, the authors demonstrated that [ 18 F]AmBF 3 -Tz is a promising radiolabeling agent for biomolecules.…”

“…Based on the use of TTCO ligation, a PET probe [ 18 F]­TTCO-Cys-exendin-4, prepared in a high specific activity, demonstrated the higher specific binding to the GLP-1 receptor (GLP-1R) and lower background-to-tumor ratio for imaging transplanted islets in comparison with the radiometal-labeled exendin-4 . Two Tyr octreotide (TOC)-based radiotracers were synthesized using IEDDA between a [ 18 F]­F-Tz derivative with a 19 F– 18 F-exchange-generated AmBF 3 moiety and a TCO-modified octreotide precursor with PEG linkers . In this study, the authors demonstrated that [ 18 F]­AmBF 3 -Tz is a promising radiolabeling agent for biomolecules.…”

Peptide-based positron emission tomography probes: current strategies for synthesis and radiolabelling

“…Since then, The AmBF 3 -chemistry has been utilised for direct IEX radiolabelling of various other peptides. 38,39 The last example regards the work of Otaru et al 40 who developed a novel prosthetic group [ 18 F]AmBF 3 tetrazine ([ 18 F]-AmBF 3 -Tz) suitable for the chemoselective radiolabelling of trans-cyclooctene (TCO)-modified biomolecules. As a model system, they radiolabelled two Tyr3 -octreotides (TOCs), analogues of somatostatin 41 , in a proof-of-concept study evaluating the influence of the novel prosthetic group on the pharmacokinetics of the wellknown peptide analogues in vivo.…”

Radiolabelling of peptides with tetrazine ligation based on the inverse electron-demand Diels–Alder reaction: rapid, catalyst-free and mild conversion of 1,4-dihydropyridazines to pyridazines

“…Based on our investigation with AmBF 3 -TOC derivatives radiolabelled with uorine-18 using the tetrazine ligation, we concluded that the oxidized pyridazine is extremely stable, resisting reduction to DHPs even in vivo. 19 Recently, Litau et al reported several side-products during radiometal labelling of peptides with IEDDA-based tetrazine ligation. 20 In their study, DOTA-GA-Tz and NODA-GA-Tz were radiolabelled with gallium-68 and copper-64 prior to the IEDDAmediated conjugation to the TCO-peptide, which resulted in formation of unknown side products.…”