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

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...

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Bibliographic Details
Published in:Bioconjugate chemistry 2021-08, Vol.32 (8), p.1554-1558
Main Authors: Jallinoja, Vilma I. J, Carney, Brandon D, Zhu, Meiying, Bhatt, Kavita, Yazaki, Paul J, Houghton, Jacob L
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Carcinoembryonic antigen
Carcinoembryonic Antigen - analysis
Emission analysis
Ferrous Compounds - chemistry
Humans
Immunoconjugates - chemistry
In vivo methods and tests
Macrocyclic Compounds - chemistry
Male
Metallocenes - chemistry
Mice
Mice, Nude
Modularity
Nuclear medicine
PC-3 Cells
Peg3 protein
Positron emission
Positron emission tomography
Prostatic Neoplasms - diagnostic imaging
Radiation dosage
Radiopharmaceuticals - chemistry
Supramolecular compounds
Tomography
Xenografts
Xenotransplantation
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Summary: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 68Ga-radiolabeled ferrocene guest radioligand ([68Ga]­Ga-NOTA-PEG3-NMe2-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 [68Ga]­Ga-NOTA-PEG3-NMe2-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).
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.1c00280