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

Autor:	Palle Rasmussen, Andreas Tue Ingemann Jensen, Pramod Kumar Ek, Tina Binderup, Constance E Grandjean, Thomas Lars Andresen, Andreas Kjaer
Rok vydání:	2017
Předmět:	Biodistribution Time Factors Polymers Nanotechnology 02 engineering and technology 010402 general chemistry Nanomedicine/methods 01 natural sciences Biochemistry Micelle Polyethylene Glycols Analytical Chemistry Mice Polymers/chemistry In vivo Positron Emission Tomography Computed Tomography Drug Discovery Copolymer Animals Tissue Distribution Radiology Nuclear Medicine and imaging Micelles Spectroscopy Acetic Acid Chemistry Organic Chemistry Acetic Acid/chemistry 021001 nanoscience & nanotechnology 0104 chemical sciences Polyethylene Glycols/chemistry Nanomedicine Copper Radioisotopes Drug delivery Biophysics Female Copper-64 0210 nano-technology Positron Emission Tomography Computed Tomography/methods Ex vivo
Zdroj:	Jensen, A I, Binderup, T, Ek, P K, Grandjean, C E, Rasmussen, P H, Kjaer, A & Andresen, T L 2017, ' 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 ', Journal of Labelled Compounds and Radiopharmaceuticals, vol. 60, no. 8, pp. 366-374 . https://doi.org/10.1002/jlcr.3510
ISSN:	0362-4803
DOI:	10.1002/jlcr.3510
Popis:	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 with 64 Cu 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 with 64 Cu and compared in vivo in tumor-bearing mice, with free 64 Cu 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 (free 64 Cu). 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.
Databáze:	OpenAIRE
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