<sup>68</sup>Ga-Labeled Trastuzumab Fragments for ImmunoPET Imaging of Human Epidermal Growth Factor Receptor 2 Expression in Solid Cancers

Suman, Shishu Kant; Mukherjee, Archana; Pandey, Usha; Ak, Chakraborty; Rakshit, Sutapa; Tawate, Megha; Sarma, Haladhar Dev

doi:10.1089/cbr.2022.0042

“…The affinity of trastuzumab for the HER2-ECD at 20ºC was previously reported by SPR with values ranging from 100 pM-9.4 nM, and these reports often agree on a KD ~0.5 nM for the Fab fragment. 30,31,32 It is typical for solution-phase assays of mAbs to observe higher affinities than surface-based techniques. 17,18 However, the rank-order is sufficient to inform most drug development applications.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

Greenway,

Wang

2024

Preprint

0

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The rapid growth of therapeutic monoclonal antibodies demands greater accessibility to scalable methods of evaluating antigen binding. Homogenous TR-FRET is ideal for preliminary screening but has not been reported to assay these interactions due to their high-affinity and complex solution-phase kinetics. Here we report the development of a competition assay to rank-order the relative affinities of these drugs for a common antigen. The assay is compatible with automation, requires no modification of the analytes, and measures affinities as low as single-digit picomolar. We further demonstrate applications to inform the development of antibody-drug conjugates. The assay may aid discovery and manufacturing of therapeutic antibodies as a low-cost, high-throughput alternative to existing technologies.

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“…Immunohistochemistry was used to successfully confirm the identification of breast and lymphatic lesions detected with this 68 Ga-NOTA-F(ab') 2 -trastuzumab probe. Suman et al ( 2023 ) also demonstrated that 68 Ga-NOTA-F(ab') 2 -trastuzumab was capable of identifying tumor cells overexpressing HER2. Lam et al ( 2017 ) similarly evaluated changes in the expression of HER2 over the course of trastuzumab treatment using a 64 Cu-NOTA-pertuzumab F(ab') 2 probe, thereby delivering a lower dose of whole-body radiation.…”

Section: Pet/ct Molecular Probes Targeting Her2mentioning

confidence: 98%

Molecular probes targeting HER2 PET/CT and their application in advanced breast cancer

Gao,

Liu,

Wang

et al. 2024

J Cancer Res Clin Oncol

2

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Purpose Human epidermal growth factor receptor 2 (HER2)-positive breast cancer cases are among the most aggressive breast tumor subtypes. Accurately assessing HER2 expression status is vital to determining whether patients will benefit from targeted anti-HER2 treatment. HER2-targeted positron emission tomography (PET/CT) is noninvasive, enabling the real-time evaluation of breast cancer patient HER2 status with accuracy. Methods We summarize the research progress of PET/CT targeting HER2 in breast cancer, focusing on PET/CT molecular probes targeting HER2 and their clinical application in the management of advanced breast cancer. Results At present, a variety of different HER2 targeted molecular probes for PET/CT imaging have been developed, including nucleolin-labeled antibodies, antibody fragments, nanobodies, and peptides of various affinities, among others. HER2-targeted PET/CT can relatively accurately evaluate HER2 expression status in advanced breast cancer patients. It has good performance in the early detection of small HER2-positive lesions, evaluation of HER2 status in lesions that cannot be readily biopsied, evaluation of the heterogeneity of multiple metastases, identification of lesions with altered HER2 status, and evaluation of the efficacy of anti-HER2 drugs. Conclusion HER2-targeted PET/CT offers a promising noninvasive approach for real-time assessment of HER2 status，which can be guide targeted treatment for HER2-positive breast cancer patients. Future prospective clinical studies will be invaluable for fully evaluating the importance of HER2-targeted molecular imaging in the management of breast cancer.

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Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

Greenway,

Wang

2024

ACS Med. Chem. Lett.

0

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The rapid growth of therapeutic monoclonal antibodies demands greater accessibility to scalable methods of evaluating antigen binding. Homogenous TR-FRET is ideal for preliminary screening but has not been reported to assay these interactions due to their high-affinity and complex solution-phase kinetics. Here we report the development of a competition assay to rank-order the relative affinities of these drugs for a common antigen. The assay is compatible with automation, requires no modification of the analytes, and measures affinities as low as single-digit picomolar. We further demonstrate applications to inform the development of antibody-drug conjugates. The assay may aid discovery and manufacturing of therapeutic antibodies as a low-cost, high-throughput alternative to existing technologies.

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⁶⁸Ga-Labeled Trastuzumab Fragments for ImmunoPET Imaging of Human Epidermal Growth Factor Receptor 2 Expression in Solid Cancers

Cited by 3 publications

References 30 publications

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

Molecular probes targeting HER2 PET/CT and their application in advanced breast cancer

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

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68Ga-Labeled Trastuzumab Fragments for ImmunoPET Imaging of Human Epidermal Growth Factor Receptor 2 Expression in Solid Cancers

Cited by 3 publications

References 30 publications

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

Molecular probes targeting HER2 PET/CT and their application in advanced breast cancer

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

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Product

Resources

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⁶⁸Ga-Labeled Trastuzumab Fragments for ImmunoPET Imaging of Human Epidermal Growth Factor Receptor 2 Expression in Solid Cancers