Development of a Chimeric Antigen-Binding Fragment Directed Against Human Galectin-3 and Validation as an Immuno-Positron Emission Tomography Tracer for the Sensitive <i>In Vivo</i> Imaging of Thyroid Cancer

Peplau, Emanuel; Rose, Francesco De; Reder, Sybille; Mittelhäuser, Markus; Scafetta, Giorgia; Schwaiger, Markus; Bartolazzi, Armando; Skerra, Arne; D’Alessandria, Calogero

doi:10.1089/thy.2019.0670

Cited by 13 publications

(9 citation statements)

References 36 publications

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“…Some studies reported that serum galectin-3 levels were higher in thyroid cancer patients, although inconsistencies exist across studies [ 20 ]. Additionally, radiolabeled antibodies or antigen-binding fragments against galectin-3 have been evaluated as molecular imaging probes in animal models [ 21 ]. Therefore, it is intriguing to assess the therapeutic potential of targeting galectin-3 in thyroid cancer.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells

Lee

Hsu

et al. 2021

International Journal of Endocrinology

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Accumulating evidence suggests that galectin-3 is a histologic marker of thyroid cancer. However, the pharmacological lectin-based approach has not been well studied. In the present study, we aimed to investigate the therapeutic potential of novel galectin-3 inhibitors by treating thyroid cancer cells with different concentrations of GB1107 or TD139. At high doses, TD139, but not GB1107, reduced cell viability and clonogenicity of thyroid cancer cells. TD139 induced apoptosis of thyroid cancer cells, as evident by an increase in the percentage of sub-G1 cells on cell cycle analysis, caspase-3 activation, and PARP1 cleavage. Either GB1107 or TD139 significantly inhibited cell coherence and counteracted anoikis resistance. Both inhibitors decreased migratory and invasive abilities in a dose-dependent manner. Furthermore, GB1107 and TD139 treatment attenuated AKT phosphorylation and decreased the expression of β-catenin and MMP2. In conclusion, these novel galectin-3 inhibitors suppressed the anoikis resistance, motility, and invasive capacity of thyroid cancer cells at least partly through the AKT/β-catenin pathway. Galectin-3 inhibitors are potentially suitable for preclinical evaluation of treatment and/or prevention of metastatic spread in thyroid cancer.

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Section: Discussionmentioning

confidence: 99%

Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells

Lee

Hsu

et al. 2021

International Journal of Endocrinology

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“…At present, the relevance of galectin-3 in the context of thyroid cancer is mainly focused on cancer diagnosis and cancer imaging (15,31). However, a limited number of experimental studies have suggested a contribution of galectin-3 in the apoptosis (11), proliferation (10,11) and migration (28) of thyroid tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Galectin‑3 promotes the adhesion, but not the migration of thyroid carcinoma cells in a β‑galactoside‑specific manner

Winter

Glassmann²,

Kraus

et al. 2021

World Acad Sci J

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In thyroid carcinoma cells, the soluble β-galactosidespecific lectin, galectin-3, is extra-and intracellularly expressed and plays a significant role in thyroid cancer diagnosis. The functional relevance of this molecule, particularly in its extracellular environment however, warrants further elucidation. To gain insight into this topic, the present study characterized principal functional properties of galectin-3 in 3 commonly used thyroid carcinoma cell lines (B-CPAP, Cal-62 and FTC-133) that express the molecule intra-and extracellulary. Cell-intrinsic galectin-3 harbors a functional carbohydrate recognition domain as determined by affinity purification. Moreover, cell surface expressed galectin-3 can be partially removed by treatment with lactose or asialofetuin, but not with sucrose. Thyroid carcinoma cells adhere to substrate-bound galectin-3 in a β-galactoside-specific manner, whereby only cell adhesion, but not cell migration is promoted. Thus, thyroid tumor cells harbor functional active galectin-3 that, inter alia, specifically interacts with cell surface-expressed molecular ligands in a β-galactoside-dependent manner, whereby the molecule can at least interfere with cell adhesion. The modulation of galectin-3 expression level or its ligands in such tumor cells could be of therapeutic interest and needs further experimental clarification.

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“…[ 89 Zr]Zr-DFO-αGal3-Fab-PAS 200 , an imunoPET probe fused with 200 Pro, Ala, and Ser residues (PAS 200 ) and conjugated with [ 89 Zr]Zr-deferoxamine ([ 89 Zr]Zr-DFO), is a recently reported Fab-based probe derived from the rat anti-Gal3 mAb. Similar to the full-size [ 89 Zr]Zr-labeled Gal-3 mAb (mentioned in Section 4.1.3) [125], the [ 89 Zr]Zr-DFO-αGal3-Fab-PAS 200 can bind the Gal-3 well [139] (Figure 12). Unlike the uptake of full-size 89 Zr-labeled Gal-3 mAb which lasts over five days after injection, the [ 89 Zr]Zr-DFO-αGal3-Fab-PAS 200 was supposed to have a shorter lasting time, but the exact time was undetermined [125].…”

Section: Fab-based Probesmentioning

confidence: 95%

“…Some Fabs have been discovered for the treatment of TC (targeting cluster of differentiation 276 [CD276] [138], etc. ), and some publications reported the potential value of Fab as diagnostic probes targeting Galectin-3 [125,139,140].…”

Section: Fab-based Probesmentioning

confidence: 99%

Next-Generation Molecular Imaging of Thyroid Cancer

Jin

Liu

Younis

et al. 2021

Cancers

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An essential aspect of thyroid cancer (TC) management is personalized and precision medicine. Functional imaging of TC with radioiodine and [18F]FDG has been frequently used in disease evaluation for several decades now. Recently, advances in molecular imaging have led to the development of novel tracers based on aptamer, peptide, antibody, nanobody, antibody fragment, and nanoparticle platforms. The emerging targets—including HER2, CD54, SHP2, CD33, and more—are promising targets for clinical translation soon. The significance of these tracers may be realized by outlining the way they support the management of TC. The provided examples focus on where preclinical investigations can be translated. Furthermore, advances in the molecular imaging of TC may inspire the development of novel therapeutic or theranostic tracers. In this review, we summarize TC-targeting probes which include transporter-based and immuno-based imaging moieties. We summarize the most recent evidence in this field and outline how these emerging strategies may potentially optimize clinical practice.

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Development of a Chimeric Antigen-Binding Fragment Directed Against Human Galectin-3 and Validation as an Immuno-Positron Emission Tomography Tracer for the Sensitive In Vivo Imaging of Thyroid Cancer

Cited by 13 publications

References 36 publications

Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells

Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells

Galectin‑3 promotes the adhesion, but not the migration of thyroid carcinoma cells in a β‑galactoside‑specific manner

Next-Generation Molecular Imaging of Thyroid Cancer

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