Study of 211Bi and 211Pb Recoils Release from 223Ra Labelled TiO2 Nanoparticles

Abstract

Nanoparticles of various materials were proposed as carriers of nuclides in targeted alpha particle therapy to at least partially eliminate the nuclear recoil effect causing the unwanted release of radioactive progeny originating in nuclear decay series of so-called in vivo generators. Here, we report on the study of 211Pb and 211Bi recoils release from the 223Ra surface-labelled TiO2 nanoparticles in the concentration range of 0.01–1 mg/mL using two phase separation methods different in their kinetics in order to test the ability of progeny resorption. We have found significant differences between the centrifugation and the dialysis used for labelled NPs separation as well as that the release of 211Pb and 211Bi from the nanoparticles also depends on the NPs dispersion concentration. These findings support our previously proposed recoils-retaining mechanism of the progeny by their resorption on the NPs surface. At the 24 h time-point, the highest overall released progeny fractions were observed using centrifugation (4.0% and 13.5% for 211Pb and 211Bi, respectively) at 0.01 mg/mL TiO2 concentration. The lowest overall released fractions at the 24 h time-point (1.5% and 2.5% for 211Pb and 211Bi respectively) were observed using dialysis at 1 mg/mL TiO2 concentration. Our findings also indicate that the in vitro stability tests of such radionuclide systems designed to retain recoil-progeny may end up with biased results and particular care needs to be given to in vitro stability test experimental setup to mimic in vivo dynamic conditions. On the other hand, controlled and well-defined progeny release may enhance the alpha-emitter radiation therapy of some tumours.

Development of 225Ac-doped biocompatible nanoparticles for targeted alpha therapy

“…The adsorption of [ 225 Ac]Ac 3+ onto the nanoparticle surface combined with an increased rate of PLGA hydrolysis would in turn increase the release of decay daughters into the dialysate [ 26 ]. The adsorption and implantation of decay daughters into adjacent PLGA nanoparticles was not significant under the experimental conditions tested (i.e., the nanoparticle concentration was approximately 8 mg/mL within the dialysis cassette) [ 78 ]. It is hypothesized that the implantation into adjacent nanoparticles is negligible because of the low electron density and amorphous structure of PLGA nanoparticles [ 79 ].…”

“…33 The enhanced retention of [ 221 Fr]Fr + and [ 213 Bi]Bi 3+ within PLGA nanoparticles may be explained by a random distribution of [ 225 Ac]AcBLPhen within each nanoparticle [ 26 ], which was likely achieved as a result of the active loading during synthesis. Future research will evaluate the implantation and potential complexation of decay daughters by adjacent PLGA nanoparticles and BLPhen ligands following the experimental setup used by Kozempel et al [ 78 ].…”

Methods for Radiolabeling Nanoparticles (Part 3): Therapeutic Use

“…As a radium dichloride ([ 223 Ra]RaCl 2 ), 223 Ra was the first α-emitting isotope with FDA marketing authorization for the treatment of bone metastases, and it was examined as a potential for targeted radionuclide therapy employing NPs as carriers. This isotope does not have the translocation problem, which is an advantage; while 225 Ac has a decay chain leading to the generation of daughter nuclides, 75% of the total alphas in the 223 Ra are delivered within a few seconds (T 1/2 = 4 s) [ 44 , 45 , 46 ].…”

“…Subsequently, the same research group studied the release of 223 Ra, 211 Bi, and 211 Pb recoils from radiolabeled NPs [ 45 ]. The results showed the low release of all the isotopes from the NPs, depending on the method used to separate them (dialysis or centrifugation).…”

“…With these experiments, the authors highlighted that false-positive results of radiolabeled NP stability can occur and, in particular, the recoiling progeny may induce artifacts. In conclusion, the authors suggested that in vitro stability tests should always be designed under real or very-similar-to-real conditions [ 45 ].…”