[161Tb]Tb-SibuDAB

We present results from the first patient in the PROGNOSTICS (NCT06343038) Phase Ia study, a prospective, single-center, single-blind trial aiming to translate [161Tb] Tb-SibuDAB to clin. radioligand therapy (RLT).In Phase Ia of the PROGNOSTICS study, mCRPC patients with stable disease on [177Lu]Lu-PSMA-I&T RLT receive two test injections: 1 GBq [177Lu]Lu-PSMA-I&T and 1 GBq [161Tb]Tb-SibuDAB, administered 3 wk apart in random order.Quant. SPECT/CT imaging was performed at 3, 24, 48, and 168 h post-injection.Tumor and organ absorbed doses were computed using a 75 keV±10% window for 161Tb (low-energy high-resolution collimator) and a 208 keV±10% window for 177Lu (mediumenergy low-penetration collimator), using a Monte Carlo OSEM reconstruction algorithm.Safety and acute toxicity (CTCAE 5.0) along with transcriptional "omics" and circulating tumor cells were evaluated after each test injection.First-in-human data suggest [161Tb]Tb-SibuDAB is a promising radiopharmaceutical for the current indication of RLT in mCRPC.The potential to enhance treatment durability against micrometastases could be further explored in a neo/adjuvant setting.The planned dose escalation study (Phase Ib of PROGNOSTICS) will assess the efficacy, toxicity, and therapeutic index of [161Tb]Tb-SibuDAB.