Evidence map›Paper›PMID 26336058›Full record

ArticlePloS one2015

Tumor Detection at 3 Tesla with an Activatable Cell Penetrating Peptide Dendrimer (ACPPD-Gd), a T1 Magnetic Resonance (MR) Molecular Imaging Agent.

Christopher D Malone, Emilia S Olson, Robert F Mattrey, Tao Jiang, Roger Y Tsien, Quyen T Nguyen

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
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

7 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Prognostic value ofFrontiers in genetics · 2022
    Article
  3. Review
  4. Review
  5. Two decades of dendrimers as versatile MRI agents: a tale with and without metals.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2018
    Review
  6. Review
  7. Article
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

6 authors at 2 institutions in 1 country.

Christopher D MaloneDepartment of Radiology, University of California, San Diego, San Diego, CA, United States of America.
Emilia S OlsonDepartment of Radiology, University of California, San Diego, San Diego, CA, United States of America.
Robert F MattreyDepartment of Radiology, University of California, San Diego, San Diego, CA, United States of America.
Tao JiangHoward Hughes Medical Institute, University of California, San Diego, San Diego, CA, United States of America.
Roger Y TsienHoward Hughes Medical Institute, University of California, San Diego, San Diego, CA, United States of America; Department of Pharmacology. University of California, San Diego, San Diego, CA, United States of America; Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, United States of America.
Quyen T NguyenDepartment of Otolaryngology-Head and Neck Surgery University of California, San Diego, San Diego, CA, United States of America.
University of California, San Diego · USHoward Hughes Medical Institute · US

Funding

Targeted Smart Nanoplatforms for Multimode ImagingP50CA128346 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI STUPACK, DWAYNE G. · 2008 to 2012
$6.9M
Traning Clinical Scientists in Radiological ImagingT32EB005970 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Eric Y Chang, Rebecca Ann Rakow-Penner · 2007 to 2026
$3.2M
Injectable reporters to image tumors and guide resectionR01CA158448 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NGUYEN, QUYEN · 2011 to 2015
$3.1M
Howard Hughes Medical InstituteNCI NIH HHS 5R01CA158448NCI NIH HHS P50 CA128346NCI NIH HHS P50-CA128346NCI NIH HHS R01 CA158448NIBIB NIH HHS 5T32EB005970-07NIBIB NIH HHS T32 EB005970
6 · The paper itself

Abstract

purposeThe ability to detect small malignant lesions with magnetic resonance imaging (MRI) is limited by inadequate accumulations of Gd with standard chelate agents. To date, no T1-targeted agents have proven superiority to Gd chelates in their ability to detect small tumors at clinically relevant field strengths. Activatable cell-penetrating peptides and their Gd-loaded dendrimeric form (ACPPD-Gd) have been shown to selectively accumulate in tumors. In this study we compared the performance of ACPPD-Gd vs. untargeted Gd chelates to detect small tumors in rodent models using a clinical 3T-MR system. MATERIALS AND

methodsThis study was approved by the Institutional-Animal Care-and-Use Committee. 2 of 4 inguinal breast fat pads of 16 albino-C57BL/6 mice were inoculated with tumor Py8119 cells and the other 2 with saline at random. MRI at 3T was performed at 4, 9, and 14 days after inoculation on 8 mice 24-hours after injection of 0.036mmol Gd/kg (ACPPD-Gd), and before and 2-3 minutes after 0.1 mmol/kg gadobutrol on the other 8 mice. T1-weighted (T1w) tumor signal normalized to muscle, was compared among the non-contrast, gadobutrol, and ACPPD-Gd groups using ANOVA. Experienced and trainee readers blinded to experimental conditions assessed for the presence of tumor in each of the 4 breast regions. Receiver operator characteristic (ROC) curves and area-under-curve (AUC) values were constructed and analyzed.

resultsTumors ≥1mm3 were iso-intense to muscle without contrast on T1w sequences. They enhanced diffusely and homogeneously by 57±20% (p<0.001) 24 hours after ACPPD-Gd and by 25±13% (p<0.001) immediately after gadobutrol. The nearly 2-fold difference was similar for small tumors (1-5mm3) (45±19% vs. 19±18%, p = 0.03). ACPPD-Gd tended to improve tumor detection by an experienced reader (AUC 0.98 vs 0.91) and significantly more for a trainee (0.93 vs. 0.82, p = 0.02) compared to gadobutrol. This improvement was more pronounced when obvious tumors (>5mm3) were removed from the ROC analysis for both the experienced observer (0.96 vs. 0.86) and more so for the trainee (0.86 vs. 0.69, p = 0.04).

conclusionACPPD-Gd enhances MMP-expressing tumors of any size at 3T 24 hours after administration, improving their detection by blinded observers when compared to non-contrast and contrast groups given commercial Gd-chelates and imaged during the equilibrium phase.

Indexed as

Contrast MediaDendrimersAllograftsAnimalsArea Under CurveFemaleHumansJurkat CellsMagnetic Resonance ImagingMammary Neoplasms, ExperimentalMatrix MetalloproteinasesMiceMice, Inbred C57BLNeoplasm ProteinsNeoplasm TransplantationROC CurveContrast MediaDendrimersMatrix MetalloproteinasesNeoplasm ProteinsPAMAM Starburst

Identifiers

PMID26336058
PMCPMC4559389
OpenAlexW2165969016

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.