title: N-Succinimidyl 3-((4-(4-[(18)F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([(18)F]SFBTMGMB): a residualizing label for (18)F-labeling of internalizing biomolecules.
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 (18)F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-Succinimidyl 3-((4-(4-[(18)F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate ([(18)F]SFBTMGMB-Boc2) was synthesized by a click reaction of an azide precursor and [(18)F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n = 15). An anti-HER2 nanobody 5F7 was labeled with (18)F using [(18)F]SFBTMGMB ([(18)F]RL-I), obtained by the deprotection of [(18)F]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 (18)F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2.
authors.affiliation: Department of Radiology and Duke University Medical Center, Durham, North Carolina, USA. ganesan.v@duke.edu.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Vaidyanathan
authors.forename: Darryl
authors.initials: D
authors.lastname: McDougald
authors.forename: Jaeyeon
authors.initials: J
authors.lastname: Choi
authors.forename: Marek
authors.initials: M
authors.lastname: Pruszynski
authors.forename: Eftychia
authors.initials: E
authors.lastname: Koumarianou
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D019275:Radiopharmaceuticals / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D006146:Guanidines; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D013388:Succinimides; C000610516:N-succinimidyl 3-((4-(4-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate; C508053:ERBB2 protein, human