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Whole-body organ-level and kidney micro-dosimetric evaluations of 64Cu-loaded HER2/ErbB2-targeted liposomal doxorubicin (64Cu-MM-302) in rodents and primates

Overview of attention for article published in EJNMMI Research, April 2015
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Title
Whole-body organ-level and kidney micro-dosimetric evaluations of 64Cu-loaded HER2/ErbB2-targeted liposomal doxorubicin (64Cu-MM-302) in rodents and primates
Published in
EJNMMI Research, April 2015
DOI 10.1186/s13550-015-0096-0
Pubmed ID
Authors

Daniel F Gaddy, Helen Lee, Jinzi Zheng, David A Jaffray, Thomas J Wickham, Bart S Hendriks

Abstract

Features of the tumor microenvironment influence the efficacy of cancer nanotherapeutics. The ability to directly radiolabel nanotherapeutics offers a valuable translational tool to obtain biodistribution and tumor deposition data, testing the hypothesis that the extent of delivery predicts therapeutic outcome. In support of a first in-human clinical trial with (64)Cu-labeled HER2-targeted liposomal doxorubicin ((64)Cu-MM-302), a preclinical dosimetric analysis was performed. Whole-body biodistribution and pharmacokinetic data were obtained in mice that received (64)Cu-MM-302 and used to estimate absorbed radiation doses in normal human organs. PET/CT imaging revealed non-uniform distribution of (64)Cu signal in mouse kidneys. Kidney micro-dosimetry analysis was performed in mice and squirrel monkeys, using a physiologically based pharmacokinetic model to estimate the full dynamics of the (64)Cu signal in monkeys. Organ-level dosimetric analysis of mice receiving (64)Cu-MM-302 indicated that the heart was the organ receiving the highest radiation absorbed dose, due to extended liposomal circulation. However, PET/CT imaging indicated that (64)Cu-MM-302 administration resulted in heterogeneous exposure in the kidney, with a focus of (64)Cu activity in the renal pelvis. This result was reproduced in primates. Kidney micro-dosimetry analysis illustrated that the renal pelvis was the maximum exposed tissue in mice and squirrel monkeys, due to the highly concentrated signal within the small renal pelvis surface area. This study was used to select a starting clinical radiation dose of (64)Cu-MM-302 for PET/CT in patients with advanced HER2-positive breast cancer. Organ-level dosimetry and kidney micro-dosimetry results predicted that a radiation dose of 400 MBq of (64)Cu-MM-302 should be acceptable in patients.

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Mendeley readers

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The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 2%
Unknown 44 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 16 36%
Student > Ph. D. Student 8 18%
Professor > Associate Professor 3 7%
Student > Bachelor 2 4%
Student > Postgraduate 2 4%
Other 6 13%
Unknown 8 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 13%
Medicine and Dentistry 6 13%
Pharmacology, Toxicology and Pharmaceutical Science 5 11%
Engineering 4 9%
Physics and Astronomy 3 7%
Other 11 24%
Unknown 10 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 April 2015.
All research outputs
#18,410,971
of 22,805,349 outputs
Outputs from EJNMMI Research
#334
of 556 outputs
Outputs of similar age
#193,000
of 264,354 outputs
Outputs of similar age from EJNMMI Research
#15
of 19 outputs
Altmetric has tracked 22,805,349 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 556 research outputs from this source. They receive a mean Attention Score of 2.5. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
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