Nanoreporter PET predicts the efficacy of anti-cancer nanotherapy
Open accessAbstract
The application of nanoparticle drug formulations, such as nanoliposomal doxorubicin (Doxil), is increasingly integrated in clinical cancer care. Despite nanomedicine's remarkable potential and growth over the last three decades, its clinical benefits for cancer patients vary. Here we report a non-invasive quantitative positron emission tomography (PET) nanoreporter technology that is predictive of therapeutic outcome in individual subjects. In a breast cancer mouse model, we demonstrate that co-injecting Doxil and a Zirconium-89 nanoreporter ((89)Zr-NRep) allows precise doxorubicin (DOX) quantification. Importantly, (89)Zr-NRep uptake also correlates with other types of nanoparticles' tumour accumulation. (89)Zr-NRep PET imaging reveals remarkable accumulation heterogeneity independent of tumour size. We subsequently demonstrate that mice with >25 mg kg(-1) DOX accumulation in tumours had significantly better growth inhibition and enhanced survival. This non-invasive imaging tool may be developed into a robust inclusion criterion for patients amenable to nanotherapy.
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Heterogeneous drug distribution happens for drugs of almost all sizes, and therapy shows no desired effect.
“Heterogeneous drug distribution happens for drugs of almost all sizes, and therapy shows no desired effect [131,132].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [132]
The Results section, “89Zr-NRep reveals Doxil's tumour uptake to vary vastly” (page unavailable), reports heterogeneous Doxil accumulation, but it also reports inhibited tumour growth and extended survival in treated mice. The categorical claim that therapy shows no desired effect is therefore contrary to this paper's findings. The study does not establish heterogeneous distribution for drugs of almost all sizes. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredDynamic contrast-enhanced CT has been utilized to evaluate intratumoral perfusion, permeability, and aggregation of CT contrast agent-carrying NPs in tumors in mice.
“However, dynamic contrast-enhanced (DCE)CT has been utilized to evaluate the intratumoral perfusion, permeability, and aggregation of CT contrast agent-carrying NPs in tumors in mice [19,132,133].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [132]
The Discussion describes CT as a quantitative imaging technique requiring pre- and post-contrast images, and its cited reference concerns CT imaging of liposome distribution in a rabbit tumor model. The paper does not report dynamic contrast-enhanced CT in mice or say that CT evaluated intratumoral perfusion, permeability, and nanoparticle aggregation. Its mouse tumor imaging used PET (Methods, “PET imaging”). (LLM, conf=0.77)
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- Authors
- Pérez-Medina, C., Abdel-Atti, D., Tang, J., Zhao, Y., Fayad, Z. A., Lewis, J. S., Mulder, W. J. M., & Reiner, T.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Mulder, Willem J. M.
- Reiner, Thomas
- Venue
- Nature Communications
- Published
- 2016-06-20
- Volume
- 7
- Issue
- 1
- Pages
- 11838-11838
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4915130
- OpenAlex
- W2462222248
- Cited by
- 128
- References
- 30
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 9 · 2023: 13 · 2022: 12 · 2021: 8 · 2020: 9 · 2019: 11 · 2018: 24 · 2017: 19 · 2016: 5
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (P30 CA008748)
- Centro Nacional de Investigaciones Cardiovasculares
- National Institutes of Health (CA008748)
- National Heart, Lung, and Blood Institute (R01HL118440, R01HL125703)
- National Cancer Institute (R01CA155432, R01CA172546, P30CA008748)
- National Institute of Biomedical Imaging and Bioengineering (R01EB009638, K25EB016673)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- zirconium-89, doxorubicin, pegylated liposomal doxorubicin, nanoliposomes, nanoparticle drug delivery, breast cancer, tumor accumulation, therapeutic outcome prediction, non-invasive imaging, tumor growth inhibition
- MeSH terms
- Theranostic Nanomedicine, Animals, Antibiotics, Antineoplastic, Biological Transport, Doxorubicin, Drug Administration Schedule, Female, Humans, Mammary Neoplasms, Experimental, Polyethylene Glycols, Tissue Distribution, Zirconium, Survival Analysis, Radiopharmaceuticals, Positron-Emission Tomography, Mice, Nanoparticles
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