Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases

Abstract

Patients with castration-resistant prostate cancer (CRPC) frequently have metastases to the bone, which may cause pain and lead to a deterioration in quality-of-life. Bone-seeking radiopharmaceuticals are agents which, when administered systemically, localize to the site of bone metastases and deliver focal radiation there. In this review, we will summarize the current literature on bone-targeting radiopharmaceuticals for CRPC, focusing on strontium-89, samarium-153, rhenium-186 and radium-223. We will discuss their indications, clinical efficacy, and toxicities and highlight some of the challenges in optimizing treatment with these agents. Historically, clinical trials with these drugs have failed to demonstrate survival improvements, restricting their use for palliative purposes only. Radium-223 is the first agent in this class to show an overall survival advantage in CRPC patients with bone metastases. This landmark finding will likely have a considerable impact on the treatment paradigm of bone-metastatic CRPC, and will pave the way for further developments in the future.

Palliative treatment of metastatic bone pain with radiopharmaceuticals: A perspective beyond Strontium-89 and Samarium-153

“…Overall, most clinical studies using 186 Re-HEDP to relieve pain from bone metastases have reported rates of pain relief up to 87% (Han et al, 2002). The mean duration of pain relief after the first dosage of 186 Re-HEDP was 6 weeks (Goyal and Antonarakis, 2012).…”

“…Das et al in 2009 proposed the use of 170 Tm-labelled radiopharmaceuticals as a potential alternative to 89 Sr-chloride for bone pain palliation, as it is readily available (Das et al, 2009). The long physical half-life of 170 Tm (128.6 days) can also be an advantage for this radiopharmaceutical distribution and storage compared with other radionuclides (Goyal and Antonarakis, 2012). On the other hand, the long half-life of 170 Tm has an important disadvantage in terms of radioactive contamination and disposal of contaminated waste and possibly lower biological effectiveness due the relative low dose rate per unit of time.…”

“…In the late 1980s, 186 Re (t 1/2 =3.8 d) was identified as a potential agent for palliative treatment of bone metastases and it is currently being used in phase III clinical trials (Goyal and Antonarakis, 2012). 186 Re is a combined β -and γ-emitter with a maximum β -emission of 1.07 keV and a 9% abundant γ-ray emission of 137 keV, which is suitable for gamma-camera imaging (Han et al, 2002).…”

“…Approximately 30% to 35% of the radiopharmaceutical remains in the bone, with a 10-fold higher uptake for metastatic tumor compared to healthy bone (Goyal and Antonarakis, 2012;Silberstein, 2005). The usual dosage administered is either 148 MBq (4 mCi) or 1.48 MBq/kg (40 µCi/kg), where administration of larger doses of this radiopharmaceutical result in proportionally higher myelosuppression (Silberstein, 2005).…”

“…Its blood clearance is rapid after intravenous administration and the total skeletal uptake is estimated to range between 40% and 60% of the administered activity (Goyal and Antonarakis, 2012). Unlike most bone-seeking radionuclides, excretion is predominantly via gastrointestinal tract, with less than 10% renal clearance (Lewington, 2005).…”