astatine-211-parthanatine ([²¹¹At]PTT) / Trevarx Biomedical - LARVOL DELTA

PARP-targeted theranostic approach to image and treat ovarian cancer. (SNMMI 2026) - "Our platform is based on the FDA-approved small molecule PARP inhibitor (PARPi), rucaparib, labeled with 211At for targeted alpha therapy ([211At]Parthanatrace, [211At]PTT) and 18F for PET/CT ([18F]FluorThanatrace, FTT). [211At]PTT cytotoxicity is largely independent of PARPi sensitivity but reliant on apparent PARP binding affinity and line-specific radiation sensitivity. In vivo data supports the safety and efficacy of [211At]PTT. Overall, this study highlights a novel role for theranostic radiopharmaceutical therapy in EOC."

Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA2 • PARP1 • PTEN • TP53

PARP-targeted alpha therapy for treatment of PARPi-resistant ovarian cancer with dosimetric modelling (EANM 2024) - "Astatine-211-Parathanatrace ([211At]PTT), an alpha-emitting radiopharmaceutical therapy analogue of rucaparib, binds to DNA-bound PARP-1 to induce lethal double-stranded DNA breaks. [211At]PTT cytotoxicity is largely independent of PARPi-sensitivity and more dependent on PARPi binding affinity and line-specific radiation sensitivity, supported by simulated dosimetry results. This suggests PTT may overcome PARPi-resistance. Overall, this study highlights a novel role for radiopharmaceutical therapy in PARPi-resistant BRCA1/2mut EOC."

Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2

PARP1-targeted alpha therapy enhances target expression (EANM 2024) - "[18F]FTT is a PET/CT probe that binds to active PARP1 based on the PARP inhibitor rucaparib...The next day, 370 kBq [211At]PTT was administered IV... PARP1-targeted alpha radiopharmaceutical therapy causes a transient increase in nuclear activated PARP1 expression in neuroblastoma xenografts. This creates the potential for fractionated therapy to potentially enhance the therapeutic ratio."

CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

Space- and time-heterogeneous dosimetry for in vitro targeted alpha therapy (SNMMI 2024) - "These experiments measured the inactivation of SKOV3 cells in cultures exposed during 72 hours to seven different concentrations of 211At in two different scenarios: 1) Targeted: the α-emitter is linked to a ligand ([211At]PTT) that binds to PARP1 receptors expressed on the SKOV3 cells, increasing the activity in the cell membrane until reaching binding kinetics equilibrium... We developed a novel tool within TOPAS to overcome dosimetry challenges associated with TAT. This tool expands usual methods for TAT dosimetry and serves as a robust platform for further exploration and understanding of targeted radiation treatments."

Heterogeneity • Preclinical • Oncology • PARP1

Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma. (PubMed, Commun Biol) - "Reversible hematological and marrow toxicity was observed 72 hours post-treatment at the MTD, however full recovery was evident by 4 weeks post-therapy. These data support clinical development of [At]PTT for high-risk neuroblastoma."

Journal • Preclinical • CNS Tumor • Hematological Disorders • Neuroblastoma • Oncology • Solid Tumor • PARP1