Purpose <p>Liver cancer incidence and mortality are projected to rise by 63.1% and 66.6%, respectively, by 2045. Treatment options for intermediate and advanced-stage liver cancer remain limited. Selective internal radiation therapy (SIRT) has emerged as a promising strategy for patients ineligible for surgery or those requiring tumour downstaging. This study aimed to develop a biodegradable radioactive rod labelled with Holmium-166 (¹⁶⁶Ho) for targeted theragnostic radiation therapy of liver cancer.</p> Methods <p>Non-radioactive Holmium (III) oxide-polycaprolactone (¹⁶⁵Ho-PCL) rods were synthesised using a silicone tube mould (0.65&#xa0;mm x 100&#xa0;mm). The rods were neutron-activated at the Malaysian Nuclear Agency using a 1&#xa0;MW research reactor (TRIGA MARK II, General Atomics, USA) under a thermal neutron flux of 1.5 × 10¹² n/cm²/s for 5&#xa0;h. The rods were then evaluated for their physicochemical characteristics, radioactivity assay, thermogravimetry profile and ¹⁶⁶Ho retention in phosphate buffer solution (PBS) pH 7.4 and 5.5.</p> Results <p>The fabricated ¹⁶⁵Ho-PCL rods exhibited a uniform diameter of 0.65 ± 0.01&#xa0;mm. The specific activity achieved was 25.29 ± 1.08 GBq/g, with no detectable radionuclide impurities. The ¹⁶⁶Ho retention efficiency exceeded 99% in PBS pH 7.4 and 5.5.</p> Conclusion <p>The ¹⁶⁶Ho-PCL rods demonstrated favourable physicochemical properties for intratumoural delivery, including structural integrity post-neutron activation, high specific activity, and excellent radionuclide retention. Future work will involve in-vitro cytotoxicity testing using human liver cancer (HepG2) cells, followed by dosimetry modelling, as well as in-vivo biodistribution, preclinical safety and therapeutic efficacy studies.</p>