Tumour-bearing mice were treated intravenously with 50 mg/kg gemcitabine (Hospira, Melbourne, VIC, Australia) on days 1 and 2 and 2.5 mg/kg cisplatin (Hospira) on day 1. DAB4 and Sal5 were conjugated to the bi-functional chelator DOTA-NHS (Macrocyclics, Dallas, TX, USA) as previously described
[11 (link)] and radiolabeled with 177Lu (PerkinElmer, Waltham, MA, USA). Radioimmunoconjugates were administered intravenously on day 3. The specific activity of radioimmunoconjugates ranged from 95 to 130 MBq/mg with >97% incorporation of 177Lu as determined by instant thin layer chromatography. The PARPi inhibitor Rucaparib (AG-014699; Selleck Chemicals, Houston, TX, USA) was diluted in 5% D-glucose in PBS for intraperitoneal injection at 1 or 2 mg/kg and administered daily on days 1 to 5, 30 min before chemotherapy or RIT. For in vivo antibody binding analysis, DAB4 was biotinylated with EZ-Link NHS-Biotin (Thermo Fisher) following manufacturer’s instructions. One hundred micrograms of biotin-DAB4 was administered 24 h after chemotherapy.
Free full text: Click here