TAT-10: Session IV: Nanocarriers

Kanazawa, Japan (UroToday.com) There is a substantial problem with binding the radioisotope to a molecular structure. Isotopes like Ra223 and Ac225 have decay chains that emit a total of four alphas. When the first decay occurs, the recoil of the daughter nucleus is sometimes sufficient to break the molecular bond holding the radioisotope. For the isotopes above, one of the daughter nuclei has a long enough half-life to travel through the body. This is doubly bad since not only is the alpha lost to the tumor site but the free isotope may damage healthy organs, especially the liver and kidneys.

The solution to these problems is to capture the radioisotope within a mechanical structure of a size (10’s of nanometers) and composition that alpha particles can escape but the daughter is retained. Either a coating or the composition of the nanocarrier is such that it can still be attached to antibody that targets the tumor.

Lanthanum Phosphate Nanoparticles as Carriers for Ac225, Ra223, and Ra225 for Targeted Alpha Therapy

This work investigates spherical shells with a LaPO4 core and another shell of LaPO4 core plus two layers of cold LaPO4 around the core. XRD and TEM analysis showed that the two types of nanoparticles(NP) had mean diameters of 3.4 and 6.3 nm respectively. The core LaPO4 NP retained up to 88% the Ra223 for 37 days. The core+ 2 shells NP  retained > 99.9% of the Ra223 and long-live daughter Pb211 for 27 days. For Ac225, the core + 2 shells retained parent isotope to >99.98% and the daughters to about 80% for 35 days.

Conjugation of the NP to the antibody mAB 201B was achieved using a lipomide polyethylene glycol linker. The conjugate showed an uptake of 30% injected dose/organ in targeted lung tumors.

The very high in vitro isotope and daughter retention and high in vivo uptake shows great promise for targeted alpha therapy with minimal damage to healthy organs

Presented By: Saed Mirzadeh from Nuclear Security and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN

Nanocarriers of Radium-223 for Targeted Alpha Therapy

Several nanomaterials were tested for as containers for Ra223 as well as diagnostic imaging isotopes Tc99m and F18 but in vivo studies showed best results for TiO2. Labeling yields under optimal conditions were better than 99%. 

In vivo studies injected mice directly in the tumor with approximately 200 kBq of [Ra223]TiO2  in 50 microliters of physiological saline. Over 98% of the activity remained at the injection site for the 14 day period of the study.

The ability to capture both a therapeutic agent and a diagnostic agent in the same nanocarrier is a very powerful tool for determining biodistribution in vivo.

Presented By: Jan Kozempel from Department of Nuclear Chemistry, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Czech Republic

Gold Nanoparticle-Conjugates as a Carrier of At211 in Alpha Particle Therapy

This study utilizes the strong bond between gold and astatine to develop conjugates with two biological agents: peptide Substance P (targeting glioma cells) and the antibody tastuzumab (targeting the SKOV ovarian cells). SEM, STEM, and DLS scans verified the 5 nanometer diameter of the gold nanoparticles. Labeling yield of At111 was better than 99%.

We tested the stability of the labeled gold-bioconjugates in sodium chloride solution, cysteine, and human serum for 2, 4, and 19 hours, In human blood serum and cerebrospinal fluid, less than 0.1% was found in solution.

These results show that gold nanoparticles conjugated to substance P and tastuzumab show great promise for alpha therapy to glioma cells and HER2+ breast and ovarian tumors respectively.

Presented By: Przemysław Kozminski from Institute of Nuclear Chemistry and Technology, Warsaw, Poland

Assessing Ac225-Polymersomes for Targeted Radionuclide Therapy

The aim of this study is to investigate the viability of encapsulating Ac225 in polymersomes (amphiplic block copolymers) nanoparticles for targeted alpha therapy. The nanoparticle design was optimized for Fr221 and Bi213 daughters with the help of the Geant4 Monte Carlo simulation package.

In vitro studies with a 3D spheroidal tumor model showed that the polymersome nanoparticles had accumulated in the outer layer in less than one day. After four days, the nanoparticles were distributed fairly uniformly throughout the spheroid. A decrease in tumor growth was observed with a dose as small as 0.1 kBq. With a dose of 1 kBq, the tumor showed significant shrinkage and higher doses cause complete destruction. A more conventional delivery system such as Ac225-DPTA shows reduced effect on the tumor likely due to poorer penetration.

Additional in vivo studies to measure the daughter retention are needed.

Presented By: Robin M. de Kruijff from Radiation Science and Technology, Delft University of Technology, Delft, the Netherlands

Written By: William Carithers, Lawrence Berkeley National Laboratory

at the 10th International Symposium on Targeted Alpha Therapy (TAT-10)  May 31 - June 1, 2017 - Kanazawa, Japan.
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