First-in-human Study of a 99mTc-Labeled Single-Domain Antibody for SPECT/CT Assessment of HER2 Expression in Breast Cancer

Zhao, Lei; Liu, Changcun; Xing, Yan; He, Jin; O’Doherty, Jim; Huang, Wenhua; Zhao, Jinhua

doi:10.21203/rs.3.rs-356098/v1

Cited by 3 publications

(4 citation statements)

References 47 publications

(66 reference statements)

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“…For the moment, three 99m Tc-labeled HER2 imaging agents passed clinical evaluation [18,21,22]. The scaffold-protein-based agents [ 99m Tc]Tc-(HE)3-G3 and [ 99m Tc]Tc-ADAPT6 revealed the difference between clinically HER2-positive and HER2-negative breast cancer tumors [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…The scaffold-protein-based agents [ 99m Tc]Tc-(HE)3-G3 and [ 99m Tc]Tc-ADAPT6 revealed the difference between clinically HER2-positive and HER2-negative breast cancer tumors [21,22]. In the case of 99m Tc-labeled sdAb NM-02 [18], a number of clinically HER2-negative tumors had higher SUV values than HER2-positive in the Phase I clinical study, i.e. the tumor uptake did not match the expression level.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike full-length IgG, such agents permit a highcontrast imaging within 2-4 h after injection [1,2,16]. Several imaging probes, including 99m Tc-and 68 Ga-labeled single-domain antibodies [17,18], 111 In-and 68 Ga-labeled affibody molecules [19,20], 99m Tc-labeled ADAPT6 [21] and DARPin G3 [22] were investigated in clinical trials. These studies have demonstrated that the use of such probes is well-tolerated, not associated with any measurable toxicity and ensures a low absorbed dose burden for patients.…”

Section: Introductionmentioning

confidence: 99%

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Direct in Vivo Comparison of <sup>99m</sup>Tc-labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy

Tolmachev¹,

Bodenko²,

Oroujeni³

et al. 2022

Preprint

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Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratifcation of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies and thereby the treatment will be more personalized and efficient. Phase I clinical evaluation of two scaffold protein-based imaging probes, [99mTc]Tc-(HE)3-G3 and [99mTc]Tc-ADAPT6, demonstrated that their injections are safe, well-tolerated and cause low level of absorbed and equivalent doses. The goal of this preclinical study was to select the best probe for patients’ stratification and for response monitoring. Biodis-tribution of both tracers was compared in mice bearing SKOV-3 xenografts with high HER2 ex-pression and MDA-MB-468 xenografts with very low expression. Changes in accumulation of both probes in SKOV-3 tumors 24 h after injection of trastuzumab were evaluated. Both [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 permitted high contrast imaging of HER2-expressing tumors and clear discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-ADAPT6 has better preconditions for higher sensitivity and specificity of stratification. On the other hand, [99mTc]Tc-(HE)3-G3 is capable to sense the decrease of HER2 expression on re-sponse to trastuzumab therapy only 24 h after injection of loading dose. This indicates that this tracer would be better for monitoring early response to such treatment. Results of this study should be considered in planning of further clinical development of HER2 imaging probes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Direct in Vivo Comparison of <sup>99m</sup>Tc-labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy

Tolmachev¹,

Bodenko²,

Oroujeni³

et al. 2022

Preprint

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show abstract

“…For early-stage cancer, antibodies targeting BC cell surface antigens such as CEA, MUC1, and L6 had been employed (68). Technitium-labeled anti-CEA Fab′ fragments showed 94% more sensitivity in breast tumors in a small clinical trial (133). 90 Y-labeled humanized BrE3 antibody against MUC1 displayed a promising anti-tumor effect in a clinical trial (134,135).…”

Section: Radionuclide Treatment In Breast Cancermentioning

confidence: 99%

The application of radionuclide therapy for breast cancer

Musket,

Davern,

Elam

et al. 2024

Front. Nucl. Med.

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Radionuclide-mediated diagnosis and therapy have emerged as effective and low-risk approaches to treating breast cancer. Compared to traditional anatomic imaging techniques, diagnostic radionuclide-based molecular imaging systems exhibit much greater sensitivity and ability to precisely illustrate the biodistribution and metabolic processes from a functional perspective in breast cancer; this transitions diagnosis from an invasive visualization to a noninvasive visualization, potentially ensuring earlier diagnosis and on-time treatment. Radionuclide therapy is a newly developed modality for the treatment of breast cancer in which radionuclides are delivered to tumors and/or tumor-associated targets either directly or using delivery vehicles. Radionuclide therapy has been proven to be eminently effective and to exhibit low toxicity in eliminating both primary tumors and metastases, and even undetected tumors. In addition, the specific interaction between the surface modules of the delivery vehicles and the targets on the surface of tumor cells enables radionuclide targeting therapy, and this represents an exceptional potential for this treatment in breast cancer. This article reviews the development of radionuclide molecular imaging techniques that are currently employed for early breast cancer diagnosis and both the progress and challenges of radionuclide therapy employed in breast cancer treatment.

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Promising Diagnostic and Therapeutic Approaches Based on VHHs for Cancer Management

Cong,

Devoogdt,

Lambin

et al. 2024

Cancers

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The discovery of the distinctive structure of heavy chain-only antibodies in species belonging to the Camelidae family has elicited significant interest in their variable antigen binding domain (VHH) and gained attention for various applications, such as cancer diagnosis and treatment. This article presents an overview of the characteristics, advantages, and disadvantages of VHHs as compared to conventional antibodies, and their usage in diverse applications. The singular properties of VHHs are explained, and several strategies that can augment their utility are outlined. The preclinical studies illustrating the diagnostic and therapeutic efficacy of distinct VHHs in diverse formats against solid cancers are summarized, and an overview of the clinical trials assessing VHH-based agents in oncology is provided. These investigations demonstrate the enormous potential of VHHs for medical research and healthcare.

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First-in-human Study of a 99mTc-Labeled Single-Domain Antibody for SPECT/CT Assessment of HER2 Expression in Breast Cancer

Cited by 3 publications

References 47 publications

Direct in Vivo Comparison of <sup>99m</sup>Tc-labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy

Direct in Vivo Comparison of <sup>99m</sup>Tc-labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy

The application of radionuclide therapy for breast cancer

Promising Diagnostic and Therapeutic Approaches Based on VHHs for Cancer Management

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