Cucurbituril-Ferrocene: Host-Guest Based Pretargeted Positron Emission Tomography in a Xenograft Model.

Autor: Jallinoja VIJ; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.; Department of Radiology, Stony Brook University, Stony Brook, New York 11794, United States., Carney BD; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.; Department of Radiology, Stony Brook University, Stony Brook, New York 11794, United States., Zhu M; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States., Bhatt K; Department of Radiology, Stony Brook University, Stony Brook, New York 11794, United States., Yazaki PJ; Beckman Institute, City of Hope, Duarte, California 91010, United States., Houghton JL; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.; Department of Radiology, Stony Brook University, Stony Brook, New York 11794, United States.
Jazyk: angličtina
Zdroj: Bioconjugate chemistry [Bioconjug Chem] 2021 Aug 18; Vol. 32 (8), pp. 1554-1558. Date of Electronic Publication: 2021 Jun 22.
DOI: 10.1021/acs.bioconjchem.1c00280
Abstrakt: Pretargeted positron emission tomography is a macromolecule-driven nuclear medicine technique that involves targeting a preadministered antigen target-bound macromolecule with a radioligand in vivo, aiming to minimize the overall radiation dose. This study investigates the use of antibody based host-guest chemistry methodology for pretargeted positron emission tomography. We hypothesize that the novel pretargeting approach reported here overcomes the challenges the current pretargeting platforms have with the in vivo stability and modularity of the pretargeting components. A cucurbit[7]uril host molecule modified, anti-carcinoembryonic antigen antibody (M5A; CB7-M5A) and a 68 Ga-radiolabeled ferrocene guest radioligand ([ 68 Ga]Ga-NOTA-PEG 3 -NMe 2 -Fc) were studied as potential host-guest chemistry pretargeting agents for positron emission tomography in BxPC3 xenografted nude mice. The viability of the platform was studied via in vivo biodistribution and positron emission tomography. Tumor uptake of [ 68 Ga]Ga-NOTA-PEG 3 -NMe 2 -Fc was significantly higher in mice which received CB7-M5A prior to the radioligand injection (pretargeted) (3.3 ± 0.7%ID/g) compared to mice which only received the radioligand (nonpretargeted) (0.2 ± 0.1%ID/g).
Databáze: MEDLINE
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