Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g-1 and 188 m2g-1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.

Production and characterization of no-carrier-added 161Tb as an alternative to the clinically-applied 177Lu for radionuclide therapy.

BACKGROUND: 161Tb is an interesting radionuclide for cancer treatment, showing similar decay characteristics and chemical behavior to clinically-employed 177Lu. The therapeutic effect of 161Tb, however, may be enhanced due to the co-emission of a larger number of conversion and Auger electrons as compared to 177Lu. The aim of this study was to produce 161Tb from enriched 160Gd targets in quantity and quality sufficient for first application in patients. METHODS: No-carrier-added 161Tb was produced by neutron irradiation of enriched 160Gd targets at nuclear research reactors. The 161Tb purification method was developed with the use of cation exchange (Sykam resin) and extraction chromatography (LN3 resin), respectively. The resultant product (161TbCl3) was characterized and the 161Tb purity compared with commercial 177LuCl3. The purity of the final product (161TbCl3) was analyzed by means of γ-ray spectrometry (radionuclidic purity) and radio TLC (radiochemical purity). The radiolabeling yield of 161Tb-DOTA was assessed over a two-week period post processing in order to observe the quality change of the obtained 161Tb towards future clinical application. To understand how the possible drug products (peptides radiolabeled with 161Tb) vary with time, stability of the clinically-applied somatostatin analogue DOTATOC, radiolabeled with 161Tb, was investigated over a 24-h period. The radiolytic stability experiments were compared to those performed with 177Lu-DOTATOC in order to investigate the possible influence of conversion and Auger electrons of 161Tb on peptide disintegration. RESULTS: Irradiations of enriched 160Gd targets yielded 6-20 GBq 161Tb. The final product was obtained at an activity concentration of 11-21 MBq/µL with ≥99% radionuclidic and radiochemical purity. The DOTA chelator was radiolabeled with 161Tb or 177Lu at the molar activity deemed useful for clinical application, even at the two-week time point after end of chemical separation. DOTATOC, radiolabeled with either 161Tb or 177Lu, was stable over 24 h in the presence of a stabilizer. CONCLUSIONS: In this study, it was shown that 161Tb can be produced in high activities using different irradiation facilities. The developed method for 161Tb separation from the target material yielded 161TbCl3 in quality suitable for high-specific radiolabeling, relevant for future clinical application.