Optimized chelator and nanoparticle strategies for high-activity ¹⁰³Pd-loaded biodegradable brachytherapy seeds

Brachytherapy (BT) is routinely used in the treatment of various cancers. Current BT relies on the placement of large sources of radioactivity at the tumor site, requiring applicators that may cause local traumas and lesions. Further, they suffer from inflexibility in where they can be placed and some sources reside permanently in the body, causing potential long-term discomfort. These issues can be circumvented through injectable sources, prepared as biodegradable materials containing radionuclides that form solid seeds after administration. The level of radioactivity contained in such seeds must be sufficient to achieve substantial local irradiation. In this report, we investigate two different strategies for biodegradable BT seeds.

The first strategy entails injectable seeds based on ¹⁰³Pd-labeled palladium-gold alloy nanoparticles ([¹⁰³Pd]PdAuNPs). These were prepared by combining [¹⁰³Pd]PdH₂Cl₄ and AuHCl₄, followed by lipophilic surface coating and dispersed in lactose octaisobutyrate and ethanol (LOIB:EtOH), in overall radiochemical yield (RCY) of 83%. With the second strategy, [¹⁰³Pd]Pd-SSIB was prepared by conjugating the [16]aneS₄ chelator with lipophilic sucrose septaisobutyrate (SSIB) followed by complexation with [¹⁰³Pd]PdH₂Cl₄ (RCY = 99%) and mixed with LOIB:EtOH. [¹⁰³Pd]Pd-SSIB was likewise formulated as injectable liquid forming seeds by mixing with LOIB. Both formulations reached activities of 1.0-1.5 GBq/mL and negligible release of radioactivity after injection of 100 µL (100-150 MBq) into aqueous buffer or mouse serum of less than 1% over one month.

Both strategies for forming injectable BT seeds containing high ¹⁰³Pd activity resulted in high radiolabeling yields, high activity per seed, and high activity retention. We consider both strategies suitable for BT, with the preferable strategy using a [16]aneS₄ chelator due to its higher biodegradability.