Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

PET imaging with copper-64 as a tool for real-time in vivo investigations of the necessity for cross-linking of polymeric micelles in nanomedicine

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{1cb7828187be412e87f2f7d1940dfcf8,
title = "PET imaging with copper-64 as a tool for real-time in vivo investigations of the necessity for cross-linking of polymeric micelles in nanomedicine",
abstract = "Polymeric micelles in nanomedicine are often cross-linked to prevent disintegration in vivo. This typically requires clinically problematic chemicals or laborious procedures. In addition, cross-linking may interfere with advanced release strategies. Despite this, it is often not investigated whether cross-linking is necessary for efficient drug delivery. We used positron emission tomography (PET) imaging with64Cu to demonstrate general methodology for real-time in vivo investigations of micelle stability. Triblock copolymers with 4-methylcoumarin cores of ABC-type (PEG-PHEMA-PCMA) were functionalized in the handle region (PHEMA) with CB-TE2A chelators. Polymeric micelles were formed by dialysis and one half was core cross-linked (CL) by UV light and the other half was not (nonCL). Both CL and nonCL were radiolabeled with64Cu and compared in vivo in tumor-bearing mice, with free64Cu as control. Accumulation in relevant organs was quantified by region of interest analysis on PET images and ex vivo counting. It was observed that CL and nonCL showed limited differences in biodistribution from each other, whereas both differed markedly from control (free64Cu). This demonstrated that 4-methylcoumarin core micelles may form micelles that are stable in circulation even without cross-linking. The methodology presented here where individual unimers are radiolabeled is applicable to a wide range of polymeric micelle types.",
keywords = "Journal Article",
author = "Jensen, {Andreas I} and Tina Binderup and Ek, {Pramod Kumar} and Grandjean, {Constance E} and Rasmussen, {Palle H} and Andreas Kjaer and Andresen, {Thomas L}",
note = "Copyright {\textcopyright} 2017 John Wiley & Sons, Ltd.",
year = "2017",
month = jun,
day = "30",
doi = "10.1002/jlcr.3510",
language = "English",
volume = "60",
pages = "366--374",
journal = "Journal of Labelled Compounds and Radiopharmaceuticals",
issn = "0362-4803",
publisher = "John/Wiley & Sons Ltd",
number = "8",

}

RIS

TY - JOUR

T1 - PET imaging with copper-64 as a tool for real-time in vivo investigations of the necessity for cross-linking of polymeric micelles in nanomedicine

AU - Jensen, Andreas I

AU - Binderup, Tina

AU - Ek, Pramod Kumar

AU - Grandjean, Constance E

AU - Rasmussen, Palle H

AU - Kjaer, Andreas

AU - Andresen, Thomas L

N1 - Copyright © 2017 John Wiley & Sons, Ltd.

PY - 2017/6/30

Y1 - 2017/6/30

N2 - Polymeric micelles in nanomedicine are often cross-linked to prevent disintegration in vivo. This typically requires clinically problematic chemicals or laborious procedures. In addition, cross-linking may interfere with advanced release strategies. Despite this, it is often not investigated whether cross-linking is necessary for efficient drug delivery. We used positron emission tomography (PET) imaging with64Cu to demonstrate general methodology for real-time in vivo investigations of micelle stability. Triblock copolymers with 4-methylcoumarin cores of ABC-type (PEG-PHEMA-PCMA) were functionalized in the handle region (PHEMA) with CB-TE2A chelators. Polymeric micelles were formed by dialysis and one half was core cross-linked (CL) by UV light and the other half was not (nonCL). Both CL and nonCL were radiolabeled with64Cu and compared in vivo in tumor-bearing mice, with free64Cu as control. Accumulation in relevant organs was quantified by region of interest analysis on PET images and ex vivo counting. It was observed that CL and nonCL showed limited differences in biodistribution from each other, whereas both differed markedly from control (free64Cu). This demonstrated that 4-methylcoumarin core micelles may form micelles that are stable in circulation even without cross-linking. The methodology presented here where individual unimers are radiolabeled is applicable to a wide range of polymeric micelle types.

AB - Polymeric micelles in nanomedicine are often cross-linked to prevent disintegration in vivo. This typically requires clinically problematic chemicals or laborious procedures. In addition, cross-linking may interfere with advanced release strategies. Despite this, it is often not investigated whether cross-linking is necessary for efficient drug delivery. We used positron emission tomography (PET) imaging with64Cu to demonstrate general methodology for real-time in vivo investigations of micelle stability. Triblock copolymers with 4-methylcoumarin cores of ABC-type (PEG-PHEMA-PCMA) were functionalized in the handle region (PHEMA) with CB-TE2A chelators. Polymeric micelles were formed by dialysis and one half was core cross-linked (CL) by UV light and the other half was not (nonCL). Both CL and nonCL were radiolabeled with64Cu and compared in vivo in tumor-bearing mice, with free64Cu as control. Accumulation in relevant organs was quantified by region of interest analysis on PET images and ex vivo counting. It was observed that CL and nonCL showed limited differences in biodistribution from each other, whereas both differed markedly from control (free64Cu). This demonstrated that 4-methylcoumarin core micelles may form micelles that are stable in circulation even without cross-linking. The methodology presented here where individual unimers are radiolabeled is applicable to a wide range of polymeric micelle types.

KW - Journal Article

U2 - 10.1002/jlcr.3510

DO - 10.1002/jlcr.3510

M3 - Journal article

C2 - 28407286

VL - 60

SP - 366

EP - 374

JO - Journal of Labelled Compounds and Radiopharmaceuticals

JF - Journal of Labelled Compounds and Radiopharmaceuticals

SN - 0362-4803

IS - 8

ER -

ID: 52703645