Departmental Seminar

Metrology support for targeted radiotherapy using alpha-particle emitting radiopharmaceuticals

Dr John Keightley
National Physical Laboratory (UK)

Since radium exhibits similar chemical properties to calcium, the short-lived α-emitting radioisotope 223Ra exhibits elevated uptake in regions of the body undergoing new bone formation. Radium-223 has recently been utilised (in the form of 223RaCl2) to treat skeletal metastases associated with advanced castration-resistant hormone refractory prostate cancer in a series of clinical trials and has been approved for use in the USA by the Food and Drug Administration in May 2013. The European Commission has also recently granted marketing authorization for the use of 223RaCl2 in Europe following a positive recommendation from the European Committee for Medicinal Products for Human Use in September 2013.

In order to correctly calculate the dose delivered to patients, accurate measurements of administered activity are required and these are typically achieved in hospitals via the use of radionuclide calibrators. The aim of the work reported here was to support operators of these devices in the UK by providing both calibration factors, and instigating a new calibration service for user-supplied solutions of this radionuclide. The first step in achieving these aims was to obtain an accurate primary standardisation of a solution of 223Ra to facilitate the calibration of a suite of instruments at NPL.

Radium-223 decays via a series of α and β emitting progeny to stable 207Pb. All the decay progeny are relatively short-lived with half-lives of less than an hour. The first decay product, 219Rn, is a noble gas with a half-life of approximately 4 seconds, and standardisation techniques in which the sample remained in liquid form were preferred to avoid problems with the loss of 219Rn and subsequent short-lived contamination of counting equipment. The techniques selected were efficiency-traced liquid scintillation counting with a commercial scintillation counter (the CIEMAT/NIST technique) and 4π liquid scintillation–γ digital coincidence counting. As part of this project, new measurements were made of the photon emission intensities for 223Ra (and its progeny), which showed significant deviations from previously published work. This is significant not only to the nuclear medicine community, as 223Ra (and progeny) lie in the decay chain of 235U. The newly derived photon emission probabilities will be of major benefit to a much wider audience.

Furthermore, a significant discrepancy of the order of 9 % was identified between the liquid scintillation and coincidence counting results performed in this work and those obtained using the NIST published calibration factors for a variety of radionuclide calibrators (and used for all radioactive administrations to cancer patients to date). Following a bilateral comparison with the NIST, this discrepancy has been confirmed and recent NIST measurements now tally with those of the NPL. A great deal of work is ongoing in harmonising the release of new calibration factors to the user community in a controlled manner.

Furthermore, a new research and development program aimed at investigating the effect of a novel Targeted Thorium Conjugate (TTC) on haematological cancers has driven the need for a new primary standardisation of 227Th (the “parent” of 223Ra). I report on the recent completion of this standardisation at NPL, and I will discuss some issues related to “time-dependent calibration factors” for this nuclide, and how it is likely to impact on the accuracy of radioactive administrations to patients.

Updated:  15 January 2019/ Responsible Officer:  Director, RSPE/ Page Contact:  Physics Webmaster