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Issue 4, 2016
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N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): a residualizing label for 18F-labeling of internalizing biomolecules

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Abstract

Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the 18F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate ([18F]SFBTMGMB-Boc2) was synthesized by a click reaction of an azide precursor and [18F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n = 15). An anti-HER2 nanobody 5F7 was labeled with 18F using [18F]SFBTMGMB ([18F]RL-I), obtained by the deprotection of [18F]SFBTMGMB-Boc2, in 31.2 ± 6.7% (n = 5) conjugation efficiency. The labeled nanobody had a radiochemical purity of >95%, bound to HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62–80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with 18F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2.

Graphical abstract: N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): a residualizing label for 18F-labeling of internalizing biomolecules

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Publication details

The article was received on 02 Nov 2015, accepted on 26 Nov 2015 and first published on 01 Dec 2015


Article type: Paper
DOI: 10.1039/C5OB02258D
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Org. Biomol. Chem., 2016,14, 1261-1271

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    N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): a residualizing label for 18F-labeling of internalizing biomolecules

    G. Vaidyanathan, D. McDougald, J. Choi, M. Pruszynski, E. Koumarianou, Z. Zhou and M. R. Zalutsky, Org. Biomol. Chem., 2016, 14, 1261
    DOI: 10.1039/C5OB02258D

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