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 Journal Article
| Authors: | Zhang, H.; Kanduluru, A. K.; Desai, P.; Ahad, A.; Carlin, S.; Tandon, N.; Weber, W. A.; Low, P. S. |
| Article Title: | 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 |
| 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 by gastrointestinal tract and urinary systems. Biodistribution studies confirmed that the tumor-to-organ ratios were ≥5 for all studied organs at 1 h p.i., except kidneys, liver, and intestine, and that the tumor-to-intestine and tumor-to-kidney ratios were also improved 4 and 20 h post-injection. [64Cu]NK1R-NOTA is a promising ligand for PET imaging of NK1R-expressing tumor xenografts. Delayed imaging with [64Cu]NK1R-NOTA improves image contrast because of the continuous clearance of radioactivity from normal organs. © 2018 American Chemical Society. |
| Journal Title: | Bioconjugate Chemistry |
| Volume: | 29 |
| Issue: | 4 |
| ISSN: | 1043-1802 |
| Publisher: | American Chemical Society |
| Date Published: | 2018-04-18 |
| Start Page: | 1319 |
| End Page: | 1326 |
| Language: | English |
| DOI: | 10.1021/acs.bioconjchem.8b00063 |
| PROVIDER: | scopus |
| PUBMED: | 29466853 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2018 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work