Abstract
Protein tyrosine kinase-7 (PTK7), a member of receptor tyrosine kinase superfamily initially identified as colon carcinoma kinase-4, is highly expressed in various human malignancies. Its expression was found to correlate with aggressive biologic behaviors such as increased cell proliferation, invasiveness, and migration. Despite the importance and unmet need of imaging PTK7 in vivo, there is currently no clinically relevant method to visualize tumoral PTK7 expression noninvasively such as PET or SPECT. This study aimed to develop a specific, selective, and high-affinity PET radioligand based on single-stranded DNA aptamer to address this challenge. Sgc8, a 41-oligonucleotide that targets to PTK7, was labeled with (18)F using a 2-step radiochemical synthesis, which featured a direct 1-step radiofluorination on the distinctive spirocyclic hypervalent iodine(III) precursor to give (18)F-fluorobenzyl azide followed by copper-mediated click conjugation with Sgc8-alkyne. (18)F-Sgc8 was evaluated in vitro and in vivo in 2 cell lines, HCT116 and U87MG, which express high and low amounts of PTK7, respectively. Sgc8 was labeled efficiently with (18)F in an isolated radiochemical yield of 62% ± 2%, non-decay-corrected based on (18)F-fluo...Continue Reading
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