ArticleMolecular pharmaceutics2014
Evaluation of (89)Zr-pertuzumab in Breast cancer xenografts.
Article in Molecular pharmaceutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 82 citations in OpenAlex.
- First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging UsingJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2018Trial
- 89Zr-Trastuzumab PET/CT for Detection of Human Epidermal Growth Factor Receptor 2-Positive Metastases in Patients With Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer.Clinical nuclear medicine · 2017Trial
- Development of Antibody and Antibody Fragment-Based Radiopharmaceuticals for Cancer Imaging and Therapy.Nuclear medicine and molecular imaging · 2026Review
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- Radiolabeling of CHX-A″-DTPA-Antibody Conjugates with [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Characterization of mAb104, a mAb Targeting a Conformationally Exposed, Tumor-Specific Epitope of HER2.Molecular cancer therapeutics · 2025Article
- In vitro and in vivo evaluation of anti-HER2 antibody conjugates labelled withEJNMMI radiopharmacy and chemistry · 2025Article
- Isopeptidic Desferrioxamine Analogues: The Role of Hydroxamate Spacing for Chelation of ZrChemMedChem · 2025Article
- Evaluating TcAs for Use in Biotechnology Applications.Biotech (Basel (Switzerland)) · 2025Article
- Novel Molecular Classification of Breast Cancer with PET Imaging.Medicina (Kaunas, Lithuania) · 2024Review
- Development ofMolecular imaging and biology · 2024Article
- Molecular probes targeting HER2 PET/CT and their application in advanced breast cancer.Journal of cancer research and clinical oncology · 2024Review
- Biparatopic anti-HER2 drug radioconjugates as breast cancer theranostics.British journal of cancer · 2023Article
- Development and evaluation ofAsia Oceania journal of nuclear medicine & biology · 2023Article
- Therapeutic Response Monitoring withPharmaceutics · 2022Article
- Determining Binding Affinity (KD) of Radiolabeled Antibodies to Immobilized Antigens.Journal of visualized experiments : JoVE · 2022Article
- Radiolabeled Antibodies for Cancer Imaging and Therapy.Cancers · 2022Review
- [89Zr]ZrDFO-CR011 PET Correlates with Response to Glycoprotein Nonmetastatic Melanoma B-targeted Therapy in Triple-negative Breast Cancer.Molecular cancer therapeutics · 2022Article
- ImmunoPET: Antibody-Based PET Imaging in Solid Tumors.Frontiers in medicine · 2022Review
- Nanotechnology in the development of small and large molecule tyrosine kinase inhibitors and immunotherapy for the treatment of HER2-positive breast cancer.Journal of cancer & metastasis research · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Pertuzumab is a monoclonal antibody that binds to HER2 and is used in combination with another HER2-specific monoclonal antibody, trastuzumab, for the treatment of HER2+ metastatic breast cancer. Pertuzumab binds to an HER2 binding site distinct from that of trastuzumab, and its affinity is enhanced when trastuzumab is present. We aim to exploit this enhanced affinity of pertuzumab for its HER2 binding epitope and adapt this antibody as a PET imaging agent by radiolabeling with (89)Zr to increase the sensitivity of HER2 detection in vivo. Here, we investigate the biodistribution of (89)Zr-pertuzumab in HER2-expressing BT-474 and HER2-nonexpressing MDA-MB-231 xenografts to quantitatively assess HER2 expression in vivo. In vitro cell binding studies were performed resulting in retained immunoreactivity and specificity for HER2-expressing cells. In vivo evaluation of (89)Zr-pertuzumab was conducted in severely combined immunodeficient mice, subcutaneously inoculated with BT-474 and MDA-MB-231 cells. (89)Zr-pertuzumab was systemically administered and imaged at 7 days postinjection (p.i.) followed by terminal biodistribution studies. Higher tumor uptake was observed in BT-474 compared to MDA-MB-231 xenografts with 47.5 ± 32.9 and 9.5 ± 1.7% ID/g, respectively at 7 days p.i (P = 0.0009) and blocking studies with excess unlabeled pertuzumab showed a 5-fold decrease in BT-474 tumor uptake (P = 0.0006), confirming the in vivo specificity of this radiotracer. Importantly, we observed that the tumor accumulation of (89)Zr-pertuzumab was increased in the presence of unlabeled trastuzumab, at 173 ± 74.5% ID/g (P = 0.01). Biodistribution studies correlate with PET imaging quantification using max SUV (r = 0.98, P = 0.01). Collectively, these results illustrate that (89)Zr-pertuzumab as a PET imaging agent may be beneficial for the quantitative and noninvasive assessment of HER2 expression in vivo especially for patients undergoing trastuzumab therapy.
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Registered trials
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.