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Kill or Cure
Published in Alan Perkins, Life and Death Rays, 2021
Given the past harmful biological effects of radium it might be thought that any future medical applications would be shunned, with radium treatments cast into the realms of history. However, in 2003 workers in the Department of Oncology at the Norwegian Radium Hospital in Oslo obtained a patent for the use of radium-223 to treat bone cancer and alleviate pain from metastatic bone disease (Larsen, Henriksen and Bruland. US Patent No.: US 6,635,234 B1). Artificially produced radium-223 with a physical half-life of 11.4 days decays by releasing a series of alpha particles. Injection of radium-223 in the form of radium chloride produced dramatic results in a series of controlled clinical trials. This bone-seeking formulation has now been licenced as XofigoTM by the Bayer Pharmaceutics Company in Germany for therapeutic use in adult patients with metastatic castration-resistant prostate cancer and symptomatic bone metastases. This medicinal product is given as 6 injections each containing an activity of 55 kBq per kilogram body weight over a period of 6 months. This gives further support to the notion that a medicine is no more than a poison given at the correct dose.
Therapeutic Options for Prostate Cancer: A Contemporary Update
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sakthivel Muniyan, Jawed A. Siddiqui, Surinder K. Batra
A preclinical study showed that uptake of calcium-mimetic radioisotope, radium-223 (alpha-particle emitter) was increased in osteoblastic lesions compared to healthy bone. Patient’s bioavailability data suggests that total uptake of radium-223 was 40–60% followed by the intestine. Phase II studies showed that radium-223 reduced the SREs related pain and also improved the bone metastasis biomarker [29, 149]. In phase III study, the Alpharadin in Symptomatic PCa Patients (ALSYMPCA) trial, which was randomized, double-blind, placebo-controlled, in which 921 patients with CRPC and symptomatic bone metastases were randomly assigned to receive intravenous treatments of radium-223 at 50 kBq/kg IV monthly for six months, or placebo showed the benefit of radium-223 over placebo in median overall survival [29, 150]. Alpha-emitting radioisotopes are safer than beta emitters in terms of toxicity while having greater potency to irradiate cancer cells. The incidence of myelosuppression, which is common in beta emitters, was very low in patients treated with radium-223. Therefore, radium-223 has received regulatory approval for use in CRPC with symptomatic bone metastases.
Radionuclides in water *
Published in Jamie Bartram, Rachel Baum, Peter A. Coclanis, David M. Gute, David Kay, Stéphanie McFadyen, Katherine Pond, William Robertson, Michael J. Rouse, Routledge Handbook of Water and Health, 2015
Radium has four naturally occurring isotopes including radium-228, radium-226, radium-224, and radium-223. The most common radium isotope, radium-226 (1,600 year radioactive half-life, emits α-particles and gamma rays) is formed in the uranium-238 decay series. Radium-228 (5.75 year half-life, β-emitter) and radium-224 (3.6 day half-life, α-emitter) are both decay products in the thorium-232 decay series. Radium-223 (11.4 day half-life, α-emitter) is formed in the uranium-235 series. Because radium-224 and radium-223 have relatively short radioactive half-lives and lower relative abundance as compared to radium-226 and radium-228, they are considered a lower health risk.
Costs of radium-223 and the pharmacy preparation 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer in Dutch hospitals
Published in Journal of Medical Economics, 2023
S. W. Quist, J. H. J. Paulissen, D. N. J. Wyndaele, J. Nagarajah, R. D. Freriks
Radium-223 is a radiopharmaceutical that emits alpha radiation and targets bone metastases that has been on the Dutch market since 20139,14,15. 177Lu-PSMA-I&T is a pharmacy preparation with an almost similar mechanism of action to the commercial 177Lu-PSMA-617.16 These 177Lu-PSMA therapies target cancer cells by binding to prostate-specific membrane antigen (PSMA) receptors (present in over 80% of mCRPC patients) and emitting beta radiation.17 The commercial16177Lu-PSMA-617 has recently received approval from the European Commission for the treatment of progressive PSMA-positive mCRPC; however, the time frame in which 177Lu-PSMA-617 will receive reimbursement in the Netherlands is uncertain as the Dutch reimbursement process for hospital drugs varies in duration (median duration is 420 days).18,19 The SPLASH trial is currently studying the efficacy of 177Lu-PSMA-I&T compared with abiraterone or enzalutamide in chemo-naïve patients with mCRPC.20 Although the European Medicines Agency (EMA) is yet to approve 177Lu-PSMA-I&T, the pharmacy preparation already received reimbursement in the Netherlands in 2021. Reimbursement is restricted to the treatment of mCRPC in adult men that are PSMA positive in the absence of a more suitable therapeutical.12
Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer
Published in Expert Review of Anticancer Therapy, 2022
Hina Shah, Praful Ravi, Guru Sonpavde, Heather Jacene
Radium-223 is a bone-seeking alpha-emitting radiopharmaceutical. Radium-223 is indicated for those with bone metastases, but no visceral metastases, because radium-223 specifically targets the osteoblastic activity caused by prostate cancer metastases. In the ALSYMPCA trial, OS for men who received radium-223 was 14.9 months versus 11.3 months for those who received placebo (P < 0.001) [6]. Although PSA responses are not seen very often with radium-223, quality of life metrics were improved in the radium-223 group, and longer times to declines in quality of life were observed in the radium-223 group versus the placebo group [31]. Some physicians utilize radium-223 later in the disease course when bone-only disease becomes symptomatic. However, others will use it earlier to optimize the chance of administering a full six dose course which has been shown to lead to more benefit compared to fewer than five doses [32].
The Swedish national guidelines on prostate cancer, part 2: recurrent, metastatic and castration resistant disease
Published in Scandinavian Journal of Urology, 2022
Ola Bratt, Stefan Carlsson, Per Fransson, Jon Kindblom, Johan Stranne, Camilla Thellenberg Karlsson
As second-line treatment, the guidelines recommend against the use of sequential treatment with ARTAs (abiraterone, apalutamide, darolutamide and enzalutamide) as there is no evidence of any clinically meaningful effect [24]. Provided that the patient is fit for chemotherapy, the recommended approach is to use docetaxel in case of previous ARTA treatment in the hormone sensitive setting and vice versa. For patients with bone metastatic disease only, who are not suitable for chemotherapy, radium-223 is an alternative. Radium-223 may also be used as third-line treatment. The combination of radium-223 treatment with abiraterone and prednisolone is associated with an increased risk of fractures [25], which led the European Medicines Agency to recommend that radium-223 treatment should always be combined with a bisphosphonate or denosumab plus vitamin D and calcium [26]. Cabazitaxel may also be used as second- or third-line treatment of mCRPC, but only in patients who have previously been treated with docetaxel [27]. The recommended dose for cabazitaxel is 20 mg/m2 because this dose has been shown to be as effective as and less toxic than 25 mg/m2 [28].