Dataset Information

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

ABSTRACT: 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).

SUBMITTER: Jallinoja VIJ

PROVIDER: S-EPMC9153067 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Jallinoja Vilma I J VIJ Carney Brandon D BD Zhu Meiying M Bhatt Kavita K Yazaki Paul J PJ Houghton Jacob L JL

Bioconjugate chemistry 20210622 8

Pretargeted positron emission tomography is a macromolecule-driven nuclear medicine technique that involves targeting a preadministered antigen target-bound macromolecule with a radioligand <i>in vivo,</i> 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 pl ...[more]

PMID: 34156824

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Project description:BackgroundEarly intrahepatic recurrence is common after surgical resection of hepatocellular carcinoma (HCC) and leads to increased morbidity and mortality. Insensitive and nonspecific diagnostic imaging contributes to EIR and results in missed treatment opportunities. In addition, novel modalities are needed to identify targets amenable for targeted molecular therapy. In this study, we evaluated a zirconium-89 radiolabeled glypican-3 (GPC3) targeting antibody conjugate (89Zr-αGPC3) for use in positron emission tomography (PET) for detection of small, GPC3+ HCC in an orthotopic murine model. Athymic nu/J mice received hepG2, a GPC3+ human HCC cell line, into the hepatic subcapsular space. Tumor-bearing mice were imaged by PET/computerized tomography (CT) 4 days after tail vein injection of 89Zr-αGPC3. Livers were then excised for the tumors to be identified, measured, bisected, and then serially sectioned at 500 μm increments. Sensitivity and specificity of PET/CT for 89Zr-αGPC3-avid tumors were assessed using tumor confirmation on histologic sections as the gold standard.ResultsIn tumor-bearing mice, 89Zr-αGPC3 avidly accumulated in the tumor within four hours of injection with ongoing accumulation over time. There was minimal off-target deposition and rapid bloodstream clearance. Thirty-eight of 43 animals had an identifiable tumor on histologic analysis. 89Zr-αGPC3 immuno-PET detected all 38 histologically confirmed tumors with a sensitivity of 100%, with the smallest tumor detected measuring 330 μm in diameter. Tumor-to-liver ratios of 89Zr-αGPC3 uptake were high, creating excellent spatial resolution for ease of tumor detection on PET/CT. Two of five tumors that were observed on PET/CT were not identified on histologic analysis, yielding a specificity of 60%.Conclusions89Zr-αGPC3 avidly accumulated in GPC3+ tumors with minimal off-target sequestration. 89Zr-αGPC3 immuno-PET yielded a sensitivity of 100% and detected sub-millimeter tumors. This technology may improve diagnostic sensitivity of small HCC and select GPC3+ tumors for targeted therapy. Human trials are warranted to assess its impact.

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Dataset Information

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

Publications

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

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