PURPOSE: ²²³Ra-Dichloride (²²³Ra) is a novel bone-seeking alpha-emitter that prolongs survival in patients with castration-resistant metastatic prostate cancer. We conducted a study to better profile the pharmacokinetics, pharmacodynamics, and biodistribution of this agent. METHODS: Ten patients received either 50, 100, or 200 kBq of ²²³Ra per kilogram of body weight. Subsequently, six of these ten patients received a second dose of 50 kBq/kg. Pharmacokinetics and biodistribution were assessed by serial blood sampling, planar imaging, and whole-body counting. Pharmacodynamic assessment was based on measurements of prostate-specific antigen, bone alkaline phosphatase, and serum N-telopeptide. Safety was also assessed. RESULTS: Pharmacokinetic studies showed rapid clearance of ²²³Ra from the vasculature, with a median of 14% (range 9-34%), 2% (range 1.6-3.9%), and 0.5% (range 0.4-1.0%) remaining in plasma at the end of infusion, after 4 h, and after 24 h, respectively. Biodistribution studies showed early passage into the small bowel and subsequent fecal excretion with a median of 52% of administered ²²³Ra in the bowel at 24 h. Urinary excretion was relatively minor (median of 4% of administered ²²³Ra). Bone retention was prolonged. No dose-limiting toxicity was observed. Pharmacodynamic effects were observed (alkaline phosphatase and serum N-telopeptides) in a significant fraction of patients. CONCLUSION: ²²³Ra cleared rapidly from plasma and rapidly transited into small bowel, with fecal excretion the major route of elimination. Administered activities up to 200 kBq/kg were associated with few side effects and appeared to induce a decline in serum indicators of bone turnover.
PURPOSE: ²²³Ra-Dichloride (²²³Ra) is a novel bone-seeking alpha-emitter that prolongs survival in patients with castration-resistant metastatic prostate cancer. We conducted a study to better profile the pharmacokinetics, pharmacodynamics, and biodistribution of this agent. METHODS: Ten patients received either 50, 100, or 200 kBq of ²²³Ra per kilogram of body weight. Subsequently, six of these ten patients received a second dose of 50 kBq/kg. Pharmacokinetics and biodistribution were assessed by serial blood sampling, planar imaging, and whole-body counting. Pharmacodynamic assessment was based on measurements of prostate-specific antigen, bone alkaline phosphatase, and serum N-telopeptide. Safety was also assessed. RESULTS: Pharmacokinetic studies showed rapid clearance of ²²³Ra from the vasculature, with a median of 14% (range 9-34%), 2% (range 1.6-3.9%), and 0.5% (range 0.4-1.0%) remaining in plasma at the end of infusion, after 4 h, and after 24 h, respectively. Biodistribution studies showed early passage into the small bowel and subsequent fecal excretion with a median of 52% of administered ²²³Ra in the bowel at 24 h. Urinary excretion was relatively minor (median of 4% of administered ²²³Ra). Bone retention was prolonged. No dose-limiting toxicity was observed. Pharmacodynamic effects were observed (alkaline phosphatase and serum N-telopeptides) in a significant fraction of patients. CONCLUSION: ²²³Ra cleared rapidly from plasma and rapidly transited into small bowel, with fecal excretion the major route of elimination. Administered activities up to 200 kBq/kg were associated with few side effects and appeared to induce a decline in serum indicators of bone turnover.
Authors: Sten Nilsson; Roy H Larsen; Sophie D Fosså; Lise Balteskard; Kari W Borch; Jan-Erik Westlin; Gro Salberg; Oyvind S Bruland Journal: Clin Cancer Res Date: 2005-06-15 Impact factor: 12.531
Authors: Robert F Hobbs; Hong Song; Christopher J Watchman; Wesley E Bolch; Anne-Kirsti Aksnes; Thomas Ramdahl; Glenn D Flux; George Sgouros Journal: Phys Med Biol Date: 2012-05-01 Impact factor: 3.609
Authors: C Collins; J F Eary; G Donaldson; C Vernon; N E Bush; S Petersdorf; R B Livingston; E E Gordon; C R Chapman; F R Appelbaum Journal: J Nucl Med Date: 1993-11 Impact factor: 10.057
Authors: Iain Murray; Sarah J Chittenden; Ana M Denis-Bacelar; Cecilia Hindorf; Christopher C Parker; Sue Chua; Glenn D Flux Journal: Eur J Nucl Med Mol Imaging Date: 2017-06-13 Impact factor: 9.236
Authors: Lawrence T Dauer; Matthew J Williamson; John Humm; Joseph O'Donoghue; Rashid Ghani; Robert Awadallah; Jorge Carrasquillo; Neeta Pandit-Taskar; Anne-Kirsti Aksnes; Colin Biggin; Vigdis Reinton; Michael Morris; Jean St Germain Journal: Health Phys Date: 2014-04 Impact factor: 1.316
Authors: Vivek Subbiah; Pete M Anderson; Kalevi Kairemo; Kenneth Hess; Winston W Huh; Vinod Ravi; Najat C Daw; Neeta Somaiah; Joseph A Ludwig; Robert S Benjamin; Sant Chawla; David S Hong; Funda Meric-Bernstam; Gregory Ravizzini; Eugenie Kleinerman; Homer Macapinlac; Eric Rohren Journal: Clin Cancer Res Date: 2019-02-07 Impact factor: 12.531