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Open AccessArticle

pH-Responsive Carboxymethylcellulose Nanoparticles for 68Ga-WBC Labeling in PET Imaging

1
Department of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy
2
Department of Chemistry and Industrial Chemistry, UdR INSTM—Pisa, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
3
Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa and Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
Polymers 2019, 11(10), 1615; https://doi.org/10.3390/polym11101615
Received: 17 September 2019 / Revised: 2 October 2019 / Accepted: 3 October 2019 / Published: 5 October 2019
(This article belongs to the Special Issue Pharmaceutical Polymers)
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 99mTc-HMPAO SPECT labeling, the use of 68Ga3+ 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 68Ga3+ eluted in HCL 0.05 N, from hospital suited 68Ge/68Ga generator and in absence of chelator. The first kit type approach involved the application of 68Ga3+ 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 68Ga-WBC labeling tool for PET imaging applications. View Full-Text
Keywords: carboxymethylcellulose; nanoparticles; WBC labeling; 68Ga; PET; radiolabeling; pH sensitive carboxymethylcellulose; nanoparticles; WBC labeling; 68Ga; PET; radiolabeling; pH sensitive
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Piras, A.M.; Fabiano, A.; Sartini, S.; Zambito, Y.; Braccini, S.; Chiellini, F.; Cataldi, A.G.; Bartoli, F.; de la Fuente, A.; Erba, P.A. pH-Responsive Carboxymethylcellulose Nanoparticles for 68Ga-WBC Labeling in PET Imaging. Polymers 2019, 11, 1615.

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