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pH-Responsive Carboxymethylcellulose Nanoparticles for (68)Ga-WBC Labeling in PET Imaging
Carboxymethylcellulose (CMC) is a well-known pharmaceutical polymer, recently gaining attention in the field of nanomedicine, especially as a polyelectrolyte agent for the formation of complexes with oppositely charged macromolecules. Here, we report on the application of pH-sensitive pharmaceutical...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835547/ https://www.ncbi.nlm.nih.gov/pubmed/31590371 http://dx.doi.org/10.3390/polym11101615 |
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author | Piras, Anna Maria Fabiano, Angela Sartini, Stefania Zambito, Ylenia Braccini, Simona Chiellini, Federica Cataldi, Angela G. Bartoli, Francesco de la Fuente, Ana Erba, Paola Anna |
author_facet | Piras, Anna Maria Fabiano, Angela Sartini, Stefania Zambito, Ylenia Braccini, Simona Chiellini, Federica Cataldi, Angela G. Bartoli, Francesco de la Fuente, Ana Erba, Paola Anna |
author_sort | Piras, Anna Maria |
collection | PubMed |
description | Carboxymethylcellulose (CMC) is a well-known pharmaceutical polymer, recently gaining attention in the field of nanomedicine, especially as a polyelectrolyte agent for the formation of complexes with oppositely charged macromolecules. Here, we report on the application of pH-sensitive pharmaceutical grade CMC-based nanoparticles (NP) for white blood cells (WBC) PET imaging. In this context and as an alternative to (99m)Tc-HMPAO SPECT labeling, the use of (68)Ga(3+) as PET radionuclide was investigated since, at early time points, it could provide the greater spatial resolution and patient convenience of PET tomography over SPECT clinical practices. Two operator-friendly kit-type formulations were compared, with the intention of radiolabeling within a short time (10 min), under mild conditions (physiological pH, room temperature) and in agreement with the actual clinically applied guidelines. NP were labeled by directly using (68)Ga(3+) eluted in HCL 0.05 N, from hospital suited (68)Ge/(68)Ga generator and in absence of chelator. The first kit type approach involved the application of (68)Ga(3+) as an ionotropic gelation agent for in-situ forming NP. The second kit type approach concerned the re-hydration of a proper freeze-dried injectable NP powder. pH-sensitive NP with 250 nm average diameter and 80% labeling efficacy were obtained. The NP dispersant medium, including a cryoprotective agent, was modulated in order to optimize the Zeta potential value (−18 mV), minimize the NP interaction with serum proteins and guarantee a physiological environment for WBC during NP incubation. Time-dependent WBC radiolabeling was correlated to NP uptake by using both confocal and FT-IR microscopies. The ready to use lyophilized NP formulation approach appears promising as a straightforward (68)Ga-WBC labeling tool for PET imaging applications. |
format | Online Article Text |
id | pubmed-6835547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68355472019-11-25 pH-Responsive Carboxymethylcellulose Nanoparticles for (68)Ga-WBC Labeling in PET Imaging Piras, Anna Maria Fabiano, Angela Sartini, Stefania Zambito, Ylenia Braccini, Simona Chiellini, Federica Cataldi, Angela G. Bartoli, Francesco de la Fuente, Ana Erba, Paola Anna Polymers (Basel) Article Carboxymethylcellulose (CMC) is a well-known pharmaceutical polymer, recently gaining attention in the field of nanomedicine, especially as a polyelectrolyte agent for the formation of complexes with oppositely charged macromolecules. Here, we report on the application of pH-sensitive pharmaceutical grade CMC-based nanoparticles (NP) for white blood cells (WBC) PET imaging. In this context and as an alternative to (99m)Tc-HMPAO SPECT labeling, the use of (68)Ga(3+) as PET radionuclide was investigated since, at early time points, it could provide the greater spatial resolution and patient convenience of PET tomography over SPECT clinical practices. Two operator-friendly kit-type formulations were compared, with the intention of radiolabeling within a short time (10 min), under mild conditions (physiological pH, room temperature) and in agreement with the actual clinically applied guidelines. NP were labeled by directly using (68)Ga(3+) eluted in HCL 0.05 N, from hospital suited (68)Ge/(68)Ga generator and in absence of chelator. The first kit type approach involved the application of (68)Ga(3+) as an ionotropic gelation agent for in-situ forming NP. The second kit type approach concerned the re-hydration of a proper freeze-dried injectable NP powder. pH-sensitive NP with 250 nm average diameter and 80% labeling efficacy were obtained. The NP dispersant medium, including a cryoprotective agent, was modulated in order to optimize the Zeta potential value (−18 mV), minimize the NP interaction with serum proteins and guarantee a physiological environment for WBC during NP incubation. Time-dependent WBC radiolabeling was correlated to NP uptake by using both confocal and FT-IR microscopies. The ready to use lyophilized NP formulation approach appears promising as a straightforward (68)Ga-WBC labeling tool for PET imaging applications. MDPI 2019-10-05 /pmc/articles/PMC6835547/ /pubmed/31590371 http://dx.doi.org/10.3390/polym11101615 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Piras, Anna Maria Fabiano, Angela Sartini, Stefania Zambito, Ylenia Braccini, Simona Chiellini, Federica Cataldi, Angela G. Bartoli, Francesco de la Fuente, Ana Erba, Paola Anna pH-Responsive Carboxymethylcellulose Nanoparticles for (68)Ga-WBC Labeling in PET Imaging |
title | pH-Responsive Carboxymethylcellulose Nanoparticles for (68)Ga-WBC Labeling in PET Imaging |
title_full | pH-Responsive Carboxymethylcellulose Nanoparticles for (68)Ga-WBC Labeling in PET Imaging |
title_fullStr | pH-Responsive Carboxymethylcellulose Nanoparticles for (68)Ga-WBC Labeling in PET Imaging |
title_full_unstemmed | pH-Responsive Carboxymethylcellulose Nanoparticles for (68)Ga-WBC Labeling in PET Imaging |
title_short | pH-Responsive Carboxymethylcellulose Nanoparticles for (68)Ga-WBC Labeling in PET Imaging |
title_sort | ph-responsive carboxymethylcellulose nanoparticles for (68)ga-wbc labeling in pet imaging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835547/ https://www.ncbi.nlm.nih.gov/pubmed/31590371 http://dx.doi.org/10.3390/polym11101615 |
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