Preclinical Evaluation of hnRNPA2B1 Antibody in Human Triple-Negative Breast Cancer MDA-MB-231 Cells via PET Imaging.
Abhinav BhiseHyun ParkWoonghee LeeSwarbhanu SarkarYeong Su HaSubramani RajkumarBora NamJeong Eun LimPhuong Tu HuynhKiwoong LeeJi-Yoon SonJung Young KimKyo Chul LeeJeongsoo YooPublished in: Pharmaceutics (2022)
Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Because TNBC lacks the expression of commonly targeted receptors, it is challenging to develop a new imaging agent for this cancer subtype. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-protein complexes that have been linked to tumor development and progression. Considering the high expression of hnRNPA2B1, an hnRNP subtype, in TNBC MDA-MB-231 cells, this study aimed to develop a novel hnRNPA2B1 antibody-based nuclear imaging agent. The hnRNPA2B1-specific antibody was radiolabeled with 64 Cu and evaluated in vitro and in vivo. The trans-cyclooctene (TCO) was functionalized on the antibody to obtain hnRNP-PEG 4 -TCO and reactive tetrazine (Tz) on the ultrastable bifunctional chelator PCB-TE2A-alkyne to yield PCB-TE2A-Tz for the inverse electron demand Diels-Alder reaction. The 64 Cu-radiolabeled antibody was administered and imaged at 1-18 h time points for conventional imaging. Alternatively, the unlabeled antibody conjugate was administered, and 48 h later radiolabeled 64 Cu-PCB-TE2A-Tz was administered to the same mice for the pretargeting strategy and imaged at the same time intervals for direct comparison. The tumor was successfully visualized in both strategies, and comparatively, pretargeting showed superior results. The 64 Cu-PCB-TE2A-Tz was successfully clicked at the tumor site with hnRNP-PEG 4 -TCO and the non-clicked were concurrently eliminated. This led to increase the tumor uptake with extremely high tumor-to-background ratio manifested by positron emission tomography (PET) imaging and biodistribution studies.
Keyphrases
- pet imaging
- positron emission tomography
- estrogen receptor
- epidermal growth factor receptor
- endothelial cells
- high resolution
- cell cycle arrest
- induced apoptosis
- poor prognosis
- drug delivery
- stem cells
- adipose tissue
- metal organic framework
- cancer therapy
- metabolic syndrome
- small molecule
- binding protein
- breast cancer cells
- mass spectrometry
- advanced non small cell lung cancer
- mesenchymal stem cells
- induced pluripotent stem cells
- cell proliferation
- papillary thyroid
- photodynamic therapy
- signaling pathway
- lymph node metastasis
- simultaneous determination
- squamous cell