Evidence map›Paper›PMID 32431501›Full record

ArticleInternational journal of nanomedicine2020

Single- and Multi-Arm Gadolinium MRI Contrast Agents for Targeted Imaging of Glioblastoma.

Rameshwar Patil, Anna Galstyan, Zachary B Grodzinski, Ekaterina S Shatalova, Shawn Wagner, Liron L Israel, Hui Ding, Keith L Black, Julia Y Ljubimova, Eggehard Holler

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of nanomedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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  4. Article
  5. Review
  6. Polymalic acid for translational nanomedicine.Journal of nanobiotechnology · 2022
    Review
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4 · The record

Corrections and comments

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

10 authors.

Rameshwar PatilNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0001-8820-8233
Anna GalstyanNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0003-2851-2545
Zachary B GrodzinskiNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ekaterina S ShatalovaNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0002-1134-5763
Shawn WagnerBiomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0001-8300-8347
Liron L IsraelNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0003-4411-5857
Hui DingNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Keith L BlackNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Julia Y LjubimovaNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Eggehard HollerNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0001-8582-2190

Funding

Nanoconjugate delivery of proliferation and checkpoint inhibitors to treat glial tumorsR01CA206220 · NCI · CEDARS-SINAI MEDICAL CENTER · PI LJUBIMOVA, JULIA Y · 2016 to 2020
$2.8M
Glial tumor image-guided surgery and treatmentR01CA209921 · NCI · TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION · PI HOLLER, EGGEHARD · 2016 to 2021
$2.6M
Differential MRI imaging for brain tumor metastases diagnosis and treatment monitoringR01CA188743 · NCI · CEDARS-SINAI MEDICAL CENTER · PI LJUBIMOVA, JULIA Y · 2015 to 2019
$2.5M
Nano immunoconjugates to treat primary and metastatic HER2 positive breast cancerR01CA230858 · NCI · CEDARS-SINAI MEDICAL CENTER · PI HOLLER, EGGEHARD, LJUBIMOVA, JULIA Y · 2019 to 2020
$1.3M
NCI NIH HHS R01 CA188743NCI NIH HHS R01 CA206220NCI NIH HHS R01 CA209921NCI NIH HHS R01 CA230858
6 · The paper itself

Abstract

backgroundPosition of gadolinium atom(s) plays a key role in contrast enhancement of gadolinium-based contrast agents. To gain a better understanding of effects of distance of gadolinium in relation to the nanoconjugate platform, we designed and synthesized single- and multi-arm ("star") gadolinium conjugates equipped with antibody and peptides for targeting. The contrast agents were studied for their tumor imaging performance in a glioma mouse model. MATERIALS AND

methodsAntibody- and peptide-targeted nano contrast agents (NCAs) were synthesized using polymalic acid platforms of different sizes. Gadolinium-DOTA and intermediates were attached as amides and targeting agents such as antibodies and peptides as thioethers. For in vivo experiments, we used human U87MG xenografts as glioma models. Magnetic resonance imaging (MRI) was performed on a Bruker BioSpec 94/20USR 9.4 T small-animal scanner. Delivery of contrast agents across the blood-brain barrier was studied by fluorescent microscopy.

resultsAll contrast agents accumulated into tumor and showed composition-dependent imaging performance. Peptide-targeted mini-NCAs had hydrodynamic diameters in the range 5.2-9.4 nm and antibody-targeted NCAs had diameters in the range 15.8-20.5 nm. Zeta potentials were in the range of -5.4--8.2 mV and -4.6--8.8 mV, respectively. NCAs showed superior relaxivities compared to MultiHance at 9.4 T. The signal enhancement indicated maximum accumulation in tumor 30-60 minutes after intravenous injection of the mouse tail vein. Only targeted NCAs were retained in tumor for up to 3 hours and displayed contrast enhancement.

conclusionThe novel targeted NCAs with star-PEG features displayed improved relaxivity and greater contrast compared with commercial MultiHance contrast agent. The enhancement by mini-NCAs showed clearance of tumor contrast after 3 hours providing a suitable time window for tumor diagnosis in clinics. The technology provides a great tool with the promise of differential MRI diagnosis of brain tumors.

Indexed as

AnimalsBrain NeoplasmsCell Line, TumorContrast MediaDisease Models, AnimalFemaleGlioblastomaHeterocyclic CompoundsHumansMagnetic Resonance ImagingMeglumineMice, NudeNanostructuresOrganometallic CompoundsXenograft Model Antitumor AssaysContrast Mediagadobenic acidgadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetateHeterocyclic CompoundsMeglumineOrganometallic Compoundsaccelerated diagnosisblood–brain barrierGd-DOTAmagnetic resonance imagingstructure variationtumor targeting

Identifiers

PMID32431501
PMCPMC7200230

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.