Synthesis and preliminary in vivo evaluation of well-dispersed biomimetic nanocrystalline apatites labeled with positron emission tomographic imaging agents.
In recent years, biomimetic synthetic apatite nanoparticles (AP-NPs), having chemical similarity with the mineral phase of bone, have attracted a great interest in nanomedicine as potential drug carriers. To evaluate the therapeutic perspectives of AP-NPs through the mechanisms of action and organs they interact with, the noninvasive monitoring of their in vivo behavior is of paramount importance. To this aim, here the feasibility to radiolabel AP-NPs ("naked" and surface-modified with citrate to reduce their aggregation) with two positron emission tomographic (PET) imaging agents ([(18)F]NaF and (68)Ga-NO2AP(BP)) was investigated. [(18)F]NaF was used for the direct incorporation of the radioisotope into the crystal lattice, while the labeling by surface functionalization was accomplished by using (68)Ga-NO2AP(BP) (a new radio-metal chelating agent). The labeling results with both tracers were fast, straightforward, and reproducible. AP-NPs demonstrated excellent ability to bind relevant quantities of both radiotracers and good in vitro stability in clinically relevant media after the labeling. In vivo PET studies in healthy Wistar rats established that the radiolabeled AP-NPs gave significant PET signals and they were stable over the investigated time (90 min) since any tracer desorption was detected. These preliminary in vivo studies furthermore showed a clear ability of citrated versus naked AP-NPs to accumulate in different organs. Interestingly, contrary to naked AP-NPs, citrated ones, which unveiled higher colloidal stability in aqueous suspensions, were able to escape the first physiological filter, i.e., the lungs, being then accumulated in the liver and, to a lesser extent, in the spleen. The results of this work, along with the fact that AP-NPs can be also functionalized with targeting ligands, with therapeutic agents, and also with metals for a combination of different imaging modalities, make AP-NPs very encouraging materials for further investigations as theranostic agents in nanomedicine.
†Institute of Nuclear Chemistry, Johannes Gutenberg-University, Fritz-Strassmann-Weg 2, 55128, Mainz, Germany.
Benedikt
B
Sandhöfer
†Institute of Nuclear Chemistry, Johannes Gutenberg-University, Fritz-Strassmann-Weg 2, 55128, Mainz, Germany.
Marian
M
Meckel
‡Instituto Andaluz de Ciencias de la Tierra (IACT), (CSIC-UGR), Laboratorio de Estudios Cristalográficos, Avenida Las Palmeras 4, 18100 Armilla, Spain.
José Manuel
JM
Delgado-López
§Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza, Italy.
Tatiana
T
Patrício
§Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza, Italy.
Anna
A
Tampieri
†Institute of Nuclear Chemistry, Johannes Gutenberg-University, Fritz-Strassmann-Weg 2, 55128, Mainz, Germany.
Frank
F
Rösch
§Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza, Italy.
Michele
M
Iafisco
D000818:Animals; D001031:Apatites / Q000737:chemistry*; D040761:Biomimetic Materials / Q000138:chemical synthesis; D003102:Colloids / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D004058:Diffusion; D005240:Feasibility Studies; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008422:Materials Testing / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D017208:Rats, Wistar; D051598:Whole Body Imaging / Q000379:methods
D001031:Apatites; D003102:Colloids; D053769:Nanocapsules; D019275:Radiopharmaceuticals
calcium phosphates; drug delivery; nanomedicine; nanoparticles; positron emission tomography