Primary standardization of ²²⁴Ra activity by liquid scintillation counting

Highlights

• A solution of ²²⁴Ra was standardized for activity by triple-to-double coincidence ratio (TDCR) liquid scintillation counting.

• Efficiency tracing and anticoincidence provided confirmatory measurements.

• Radionuclide calibrator settings determined with typical expanded (k = 2) uncertainties < 1%.

Abstract

A standard for activity of ²²⁴Ra in secular equilibrium with its progeny has been developed, based on triple-to-double coincidence ratio (TDCR) liquid scintillation (LS) counting. The standard was confirmed by efficiency tracing and 4παβ(LS)-γ(NaI(Tl)) anticoincidence counting, as well as by 4πγ ionization chamber and NaI(Tl) measurements. Secondary standard ionization chambers were calibrated with an expanded uncertainty of 0.62% (k = 2). Calibration settings were also determined for a 5 mL flame-sealed ampoule on several commercial reentrant ionization chambers (dose calibrators).

Introduction

Radium-224 (historically known as Thorium-X), daughter of ²²⁸Th, is an alkaline earth element with a half-life of 3.631(2) d (Bé et al., 2004; DDEP, 2018). Radium-224 has a complex decay chain with six short-lived daughter radionuclides, including the emission of four energetic alpha particles (Fig. 1). The first ²²⁴Ra daughter is ²²⁰Rn (half-life 55.8(3) s (Bé et al., 2004; DDEP, 2018)), followed by ²¹⁶Po, and then ²¹²Pb, which has the longest half-life of 10.64(1) h (Bé et al., 2004; DDEP, 2018) of the progeny. In recent years, ²²⁴Ra has been used as an effective tracer for monitoring coastal water mixing processes (Moore, 2000, 2003), but historically, most research surrounding ²²⁴Ra has been medically motivated. The first isotopic separation of ²²⁴Ra was reported in 1900 by Rutherford and Soddy (1900) and the first medical use was registered in 1912 by two independent scientists in Germany: Pappenheim and Bickel. The first studied oral administration of ²²⁴Ra in patients suffering from anemia and leukemia (Pappenheim and Plesch, 1912); the second researched intravenous injection of ²²⁴Ra in patients affected by ankylosing spondylitis (Bickel, 1912), an inflammatory disease of the vertebral column. Numerous other medical applications for ²²⁴Ra were researched, especially before and immediately after World War II. Poor knowledge of the effects of ionizing radiation, particularly on growing and developing tissues, likely account for many of the very serious reported side-effects (e.g., Spiess, 2002). Difficulties were probably also compounded by the lack of a reliable method for measuring activity, which was initially calculated in electrostatic units, an obsolete unit used until 1969 for ²²⁴Ra medical dosage (Wick and Gössner, 1993). More recently, a suspension of injectable calcium carbonate microparticles labeled with ²²⁴Ra has shown promise in preclinical studies for treatment of cavitary micro-metastatic cancer (Westrøm et al., 2018, 2018b).

This therapeutic use of ²²⁴Ra exploits the high energy and short range of alpha particles to induce non-repairable double-strand DNA breaks with minimal toxicity to surrounding healthy tissues. Prior to commencing clinical trials, it is essential to develop a radioactivity standard for ²²⁴Ra to assure consistent dosage administration and to accurately calculate dose-response relationships.

We report here a series of primary activity determinations using several liquid scintillation (LS) counting-based methods. Triple-to-double coincidence ratio (TDCR) LS counting, CIEMAT-NIST efficiency tracing (CNET) with tritium, and live-timed 4παβ(LS)-γ(NaI) anticoincidence counting (LTAC) were all employed (Broda et al., 2007; Bobin, 2007; Fitzgerald et al., 2015). These measurements were complemented by Monte Carlo simulations to model instrument responses, ensuring appropriate corrections and establishing theoretical links with 4πγ ionization chamber or NaI(Tl) measurements. Through gamma-ray spectrometry with high-purity germanium (HPGe) detectors and ionization chamber measurements, we place our activity measurements in context with previous and contemporary efforts.