Nuclear Medicine Therapy With 223Radium-dichloride for Osseous Metastases in Prostate Carcinoma

Abstract

Painful osseous metastasis resulting from castration-resistant prostate carcinoma is a common clinical problem. Historically, nuclear medicine offered several palliative beta-emitting radiopharmaceuticals targeting the skeleton with the goal of decreasing pain. However, these have largely been replaced by the alpha-emitting agent 223radium (Ra). 223Ra received Food and Drug Administration approval in 2013 for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases without visceral metastases. 223Ra offers an improved therapeutic profile due to its alpha-particle emissions resulting in a relatively higher linear energy transfer and lower particle range compared with beta-emitters. 223Ra also has demonstrated to increase overall survival in patients and to delay adverse skeletal events. Running a successful clinical nuclear therapy program with 223Ra requires a multidisciplinary team approach and this article suggests an implementation strategy from the authors’ institution. Potential new nuclear radiopharmaceuticals still under investigation offering the future possibility of radioligand therapy are also discussed briefly.

Establishing a robust radioligand therapy program: A practical approach for North American centers

“…The NRC provides significant guidance, and this is detailed in the Supplemental Information (see “Radiation Safety Guidelines for Patient Charge”). Based on those principles, 223 Ra dichloride treatment is always performed as an outpatient procedure 21,26 . 177 Lu‐based RLT and radioiodine therapy are generally considered outpatient procedures in the United States and Canada, unless a patient has specific comorbidities that increase the likelihood of serious adverse events during therapy 19,25 or cannot adhere to radiation safety guidelines at home.…”

“…Systematic checklists may be used to assist with appropriate patient selection and to identify any relevant concerns that would affect safe RLT delivery. Checklists for 223 Ra and 177 Lu-DOTATATE have been published previously, 7,19,21 highlighting diagnostic imaging as a part of the theranostic approach and a key component of patient selection for RLT. Before almost all radionuclide-based therapies, appropriate pre-therapy imaging is recommended to confirm the expression of the target/biomarker.…”

The Role of PET and SPECT Imaging in Prostate Cancer Targeted Alpha Therapy: When and How?

“…In 2013, 223 Radium-dichloride ( 223 Ra-Cl2) obtained the Food and Drug Administration (FDA) approval for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients with symptomatic bone metastases, no visceral metastases and without lymph nodes greater than 30 mm [36,37]. 223 Ra is an alpha-emitter with a half-life of 11.4 days [38]; 223 Ra-Cl2 acts as a calcium analog and is taken up into sites of increased bone remodeling, such as bone metastasis, binding bone hydroxyapatite [39,40]: in skeletal metastasis, 223 Ra induces apoptosis by means of double-stranded DNA breaks [41].…”