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Colloids Surf B Biointerfaces. 2019 Jul 1;179:143-152. doi: 10.1016/j.colsurfb.2019.03.057. Epub 2019 Mar 28.

In Situ In Vivo radiolabeling of polymer-coated hydroxyapatite nanoparticles to track their biodistribution in mice.

Author information

1
Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq. 1888/2, 162 06, Prague 6, Czech Republic. Electronic address: lobaz@imc.cas.cz.
2
Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq. 1888/2, 162 06, Prague 6, Czech Republic.
3
Department of Nuclear Chemistry, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University, Břehová 7, 115 19, Prague 1, Czech Republic.
4
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hněvotínská 5, 779 00, Olomouc, Czech Republic.

Abstract

The imaging of healthy tissues and solid tumors benefits from the application of nanoparticle probes with altered pharmacokinetics, not available to low molecular weight compounds. However, the distribution and accumulation of nanoprobes in vivo typically take at least tens of hours to be efficient. For nanoprobes bearing a radioactive label, this is contradictory to the requirement of minimizing the radiation dose for patients by using as-short-as-feasible half-life radionuclides in diagnostics. Thus, we developed a two-stage diagnostic concept for monitoring long-lasting targeting effects with short-lived radioactive labels using bone-mimicking biocompatible polymer-coated and colloidally fully stabilized hydroxyapatite nanoparticles (HAP NPs) and bone-seeking radiopharmaceuticals. Within the pretargeting stage, the nonlabeled nanoparticles are allowed to circulate in the blood. Afterward, 99mTc-1-hydroxyethylidene-1.1-diphosphonate (99mTc-HEDP) is administered intravenously for in situ labeling of the nanoparticles and subsequent single-photon emission computed tomography/computed tomography (SPECT/CT) visualization. The HAP NPs, stabilized with tailored hydrophilic polymers, are not cytotoxic in vitro, as shown by several cell lines. The polymer coating prolongs the circulation of HAP NPs in the blood. The nanoparticles were successfully labeled in vivo with 99mTc-HEDP, 1 and 24 h after injection, and they were visualized by SPECT/CT over time in healthy mice.

KEYWORDS:

Bone-seeking agent; Hydroxyapatite nanoparticle; Hydroxybisphosphonate; Polyoxazoline; Radiopharmaceutical

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