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
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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. / Jensen, Andreas I; Binderup, Tina; Ek, Pramod Kumar; Grandjean, Constance E; Rasmussen, Palle H; Kjaer, Andreas; Andresen, Thomas L.
In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 60, No. 8, 2017, p. 366-374.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2017
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 - Acetic Acid/chemistry
KW - Animals
KW - Copper Radioisotopes
KW - Female
KW - Mice
KW - Micelles
KW - Nanomedicine/methods
KW - Polyethylene Glycols/chemistry
KW - Polymers/chemistry
KW - Positron Emission Tomography Computed Tomography/methods
KW - Time Factors
KW - Tissue Distribution
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: 194040096