Hydroxyapatite and Titanium Dioxide Nanoparticles: Radiolabelling and In Vitro Stability of Prospective Theranostic Nanocarriers for 223Ra and 99mTc

Abstract

Hydroxyapatite and titanium dioxide are widely used materials in a broad spectrum of branches. Due to their appropriate properties such as a large specific surface area, radiation stability or relatively low toxicity, they could be potentially used as nanocarriers for medicinal radionuclides for diagnostics and therapy. Two radiolabelling strategies of both nanomaterials were carried out by 99mTc for diagnostic purposes and by 223Ra for therapeutic purposes. The first one was the radionuclide sorption on ready-made nanoparticles and the second one was direct radionuclide incorporation into the structure of the nanoparticles. Achieved labelling yields were higher than 94% in all cases. Afterwards, in vitro stability tests were carried out in several solutions: physiological saline, bovine blood plasma, bovine blood serum, 1% and 5% human albumin solutions. In vitro stability studies were performed as short-term (59 h for 223Ra and 31 h for 99mTc) and long-term experiments (five half-lives of 223Ra, approx. 55 days). Both radiolabelled nanoparticles with 99mTc have shown similar released activities (about 20%) in all solutions. The best results were obtained for 223Ra radiolabelled titanium dioxide nanoparticles, where overall released activities were under 6% for 59 h study in all matrices and under 3% for 55 days in a long-term perspective.

Tailoring the Radionuclide Encapsulation and Surface Chemistry of La(223Ra)VO4 Nanoparticles for Targeted Alpha Therapy

“…The stability and radionuclide retention of La( 223 Ra)VO4 NPs, synthesized by procedure, C were assessed by dialyzing the NP suspension against PBS (Figure 8). The 223 Ra radiochemical yield calculated after dialysis against PBS for 15 days was 99.7 ± 0.2% (n = 3), which is comparable with that reported for intrinsically radiolabeled hydroxyapatite (Hap; 97.0 ± 0.5%) and titanium dioxide (TiO2; 99.1 ± 0.3%) NPs [26]. Although the leakage of decay daughters was not reported, the leakage or released activity of 223 Ra from Hap The 223 Ra radiochemical yield for La( 223 Ra, 140 Ba)VO 4 NPs was similar to that obtained with La( 223 Ra)PO 4 core NPs (91%) and higher than that for core + 2 shells (80%) [19].…”

“…The 223 Ra radiochemical yield calculated after dialysis against PBS for 15 days was 99.7 ± 0.2% (n = 3), which is comparable with that reported for intrinsically radiolabeled hydroxyapatite (Hap; 97.0 ± 0.5%) and titanium dioxide (TiO 2 ; 99.1 ± 0.3%) NPs [26]. Although the leakage of decay daughters was not reported, the leakage or released activity of 223 Ra from Hap NPs was significantly higher with respect to that of La( 223 Ra)VO 4 NPs [26]. The decrease in radionuclide leakage after dialysis of La( 223 Ra)VO 4 NPs against PBS may be related to the interaction of free radionuclides with phosphate species in solution, changes in NP colloidal stability, or both (Figure 8).…”

“…NPs was significantly higher with respect to that of La( 223 Ra)VO4 NPs [26]. The decrease in radionuclide leakage after dialysis of La( 223 Ra)VO4 NPs against PBS may be related to the interaction of free radionuclides with phosphate species in solution, changes in NP colloidal stability, or both (Figure 8).…”

“…The principle of surrounding α-emitting radionuclides with a high stopping power environment has been used for developing inorganic NPs. Different compounds have been studied as delivery platforms to minimize the relocation of decay daughters, including lanthanide phosphate [18][19][20][21], lanthanide vanadate [22,23], iron oxide [24,25], titanium dioxide [26,27], zeolites [28,29], barium sulfate [30,31], and gold [32]. The retention of decay daughters within inorganic NPs is based on the stopping power of each compound, the NP density, and the fraction of recoil energy that can be transferred to the NP by translational, rotational, and vibrational modes [18,20,21,33].…”

Towards the stable chelation of radium for biomedical applications with an 18-membered macrocyclic ligand

“…39,40 Doping of the Ra 2+ ion into solid-state nanoparticles, such as those of BaSO 4 , LaPO 4 , Fe 2 O 3 , TiO 2 , hydroxyapatite, and nanozeolites, has been shown to be an effective means of stabilizing this radionuclide and altering its biodistribution properties. [41][42][43][44][45][46] However, the complementary use of molecularly-targeted constructs using a BFC would enable more possibilities for radiopharmaceutical optimization via appropriate chemical modications.…”