PET-MR Guided, Pre-targeted delivery to HER2(+) Breast Cancer Model.

Ge Si, Sudath Hapuarachchige, Wojciech G Lesniak, Dmitri Artemov

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In one paragraph

Article in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Ge SiDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.

Sudath HapuarachchigeDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 401 N. Broadway, Baltimore, MD 21287, USA.

Wojciech G LesniakThe Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Baltimore, MD 21205, USA.

Dmitri ArtemovDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 401 N. Broadway, Baltimore, MD 21287, USA.ORCID 0000-0002-6837-8953

Funding

HER2-pretargeting image-guided therapy of breast cancerR01CA209884 · NCI · JOHNS HOPKINS UNIVERSITY · PI ARTEMOV, DMITRI · 2017 to 2021

$2.0M

NCI NIH HHS R01 CA209884

6 · The paper itself

Abstract

Purpose: HER2(+) metastatic breast cancer (mBC) is one of the most aggressive and lethal cancer types among females. While initially effective, targeted therapeutic approaches with trastuzumab and pertuzumab antibodies and antibody-drug conjugates (ADC) lack long-term efficacy against HER2(+) mBC and can cause severe systemic toxicity due to off-target effects. Therefore, the development of novel targeted delivery platforms that minimize toxicity and increase therapeutic efficacy is critical to the treatment of HER2(+) breast cancer (BC). A pretargeting delivery platform can minimize the non-specific accumulation and off-target toxicity caused by traditional one-step delivery method by separating the single delivery step into a pre-targeting step with high-affinity biomarker binding ligand followed by the subsequent delivery step of therapeutic component with fast clearance. Each delivery component is functionalized with bioorthogonal reactive groups that quickly react Procedures: We have successfully developed a click chemistry-based pretargeting platform for HER2(+) BC enabling PET-MR image guidance for reduced radiation dose, high sensitivity, and good soft tissue contrast. Radiolabeled trastuzumab and superparamagnetic iron-oxide carriers (uSPIO) were selected as pretargeting and delivery components, respectively. HER2(+) BT-474 cell line and corresponding xenografts were used for Results: An enhanced tumor accumulation as well as tumor-to-organ accumulation ratio was observed in pretargeted mice up to 24 h post uSPIO injection. A 40% local T Conclusions: Prolonged tumor retention and increased tumor-to-organ accumulation ratio provided a solid foundation for pretargeted image-guided delivery approach for

Indexed as

biorthogonal click chemistryCancer imagingHER2(+) breast cancerNanocarrier DeliveryPET-MRPretargetinguSPIO

Identifiers

PMID38464126

DOI10.21203/rs.3.rs-3974001/v1

PMCPMC10925432

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.