Synthesis and Evaluation of a Novel 64 Cu- and 67 Ga-Labeled Neurokinin 1 Receptor Antagonist for in Vivo Targeting of NK1R-Positive Tumor Xenografts

Bioconjugate Chemistry
Hanwen ZhangPhilip S Low

Abstract

Neurokinin 1 receptor (NK1R) is expressed in gliomas and neuroendocrine malignancies and represents a promising target for molecular imaging and targeted radionuclide therapy. The goal of this study was to synthesize and evaluate a novel NK1R ligand (NK1R-NOTA) for targeting NK1R-expressing tumors. Using a carboxymethyl moiety linked to L-733060 as a starting reagent, NK1R-NOTA was synthesized in a three-step reaction and then labeled with 64Cu (or 67Ga for in vitro studies) in the presence of CH3COONH4 buffer. The radioligand affinity and cellular uptake were evaluated with NK1R-transduced HEK293 cells (HEK293-NK1R) and NK1R nontransduced HEK293 cells (HEK293-WT) and their xenografts. Radiolabeled NK1R-NOTA was obtained with a radiochemical purity of >95% and specific activities of >7.0 GBq/μmol for 64Cu and >5.0 GBq/μmol for 67Ga. Both 64Cu- and 67Ga-labeled NK1R-NOTA demonstrated high levels of uptake in HEK293-NK1R cells, whereas co-incubation with an excess of NK1R ligand L-733060 reduced the level of uptake by 90%. Positron emission tomography (PET) imaging showed that [64Cu]NK1R-NOTA had a accumulated rapidly in HEK293-NK1R xenografts and a 10-fold lower level of uptake in HEK293-WT xenografts. Radioactivity was cleared ...Continue Reading

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Citations

Jul 12, 2019·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Ananda Kumar KanduluruPhilip S Low
Jun 6, 2018·Biomedicines·Gail L Matters, John F Harms
Aug 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paweł K HalikEwa Gniazdowska

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