Determination of the Terbium-152 half-life from mass-separated samples from CERN-ISOLDE and assessment of the radionuclide purity.

Terbium-152 is one of four terbium radioisotopes that together form a potential theranostic toolbox for the personalised treatment of tumours. As 152 Tb decay by positron emission it can be utilised for diagnostics by positron emission tomography. For use in radiopharmaceuticals and for activity measurements by an activity calibrator a high radionuclide purity of the material and an accurate and precise knowledge of the half-life is required. Mass-separation and radiochemical purification provide a production route of high purity 152Tb. In the current work, two mass-separated samples from the CERN-ISOLDE facility have been assayed at the National Physical Laboratory to investigate the radionuclide purity. These samples have been used to perform four measurements of the half-life by three independent techniques: high-purity germanium gamma-ray spectrometry, ionisation chamber measurements and liquid scintillation counting. From the four measurement campaigns a half-life of 17.8784(95) h has been determined. The reported half-life shows a significant difference to the currently evaluated half-life (ζ-score = 3.77), with a relative difference of 2.2 % and an order of magnitude improvement in the precision. This work also shows that under controlled conditions the combination of mass-separation and radiochemical separation can provide high-purity 152Tb.

Half-life determination of 155Tb from mass-separated samples produced at CERN-MEDICIS.

Terbium-155 has been identified for its potential for single-photon emission computed tomography (SPECT) in nuclear medicine. For activity measurements, an accurate and precise half-life of this radionuclide is required. However, the currently evaluated half-life of 5.32(6) d with a relative standard uncertainty of 1.1% determines the precision possible. Limited literature for the half-life measurements of this radionuclide is available and all reported investigations are prior to 1970. Further measurements are therefore needed to confirm the accuracy and improve the precision of the half-life for its use in the clinical setting. Two samples produced and mass separated at the CERN-MEDICIS facility have been measured at the National Physical Laboratory by two independent techniques: liquid scintillation counting and high-purity germanium gamma-ray spectrometry. A half-life of 5.2346(36) d has been determined from the weighted mean of the half-lives determined by the two techniques. The half-life reported in this work has shown a relative difference of 1.6% to the currently evaluated half-life and has vastly improved the precision.

The potential radio-immunotherapeutic α-emitter 227Th - part II: Absolute γ-ray emission intensities from the excited levels of 223Ra.

At the time of publication, radiopharmaceuticals labelled with thorium-227 are in clinical trials in Europe for the treatment of various types of cancer. In part I of this two-part series the primary standardisation of an aqueous solution of 227Th was reported. In part II, the activity derived from the recommended absolute γ-ray emission intensities have been compared to that from the primary standardisation techniques. This comparison showed a negative bias of 4% in the determined activity per unit mass with an 11% spread in the activities determined for the eight most intense γ-ray emissions (Iγ > 1%) from the 227Th α decay. Using the standardised 227Th, measurements of the characteristic γ-ray emissions from the 223Ra excited states were made using a calibrated HPGe γ-ray spectrometer. This has enabled the absolute intensities of 70 γ ray emissions from the 227Th α-decay to be experimentally determined. A significant improvement over the precision of the recommended normalisation scaling factor has been made, with a value of 12.470 (35) % determined. Typically, the precision of the intensities has been improved by an order of magnitude or greater than current recommended values. The correlation matrices for pairs of the most intense γ-ray emission intensities are presented.

The potential radio-immunotherapeutic α-emitter 227Th - part I: Standardisation via primary liquid scintillation techniques and decay progeny ingrowth measurements.

Thorium-227 is a potential therapeutic radionuclide for applications in targeted α-radioimmunotherapy for the treatment of various types of cancer. To provide nuclear medicine departments involved in Phase I clinical trials traceability to the SI unit of radioactivity (Bq), a standardisation of a radiochemically pure 227Th aqueous solution has been performed at the National Physical Laboratory. This was achieved via two primary liquid scintillation (LS) techniques -4π(LS)-γ digital coincidence counting (DCC) and 4π LS counting. These absolute techniques were supported by the indirect determination of the 227Th activity via the measurement of the ingrowth and decay rate of the decay progeny by both ionisations chambers and high purity germanium (HPGe) gamma-ray spectrometry. The results of the primary techniques were found to be consistent, both with each other (zeta score = 1.1) and to the decay progeny ingrowth measurements. An activity per unit mass of 20.726 (51) kBq g-1 was determined for the solution. A procedure has been developed that provided an effective separation of the 227Th from its decay progeny, which was shown by the effective time zero of the 227Th-223Ra nuclear chronometer measured by HPGe gamma-ray spectrometry.

Quantitative imaging, dosimetry and metrology; Where do National Metrology Institutes fit in?

In External Beam Radiotherapy, National Metrology Institutes (NMIs) play a critical role in the delivery of accurate absorbed doses to patients undergoing treatment. In contrast for nuclear medicine the role of the NMI is less clear and although significant work has been done in order to establish links for activity measurement, the calculation of administered absorbed doses is not traceable in the same manner as EBRT. Over recent decades the use of novel radiolabelled pharmaceuticals has increased dramatically. The limitation of secondary complications due to radiation damage to non-target tissue has historically been achieved by the use of activity escalation studies during clinical trials and this in turn has led to a chronic under dosing of the majority of patients. This paper looks to address the difficulties in combining clinical everyday practice with the grand challenges laid out by national metrology institutes to improve measurement capability in all walks of life. In the life sciences it can often be difficult to find the correct balance between pure research and practical solutions to measurement problems, and this paper is a discussion regarding these difficulties and how some NMIs have chosen to tackle these issues. The necessity of establishing strong links to underlying standards in the field of quantitative nuclear medicine imaging is highlighted. The difficulties and successes of current methods for providing traceability in nuclear medicine are discussed.

Measurement of the (109)Cd half-life.

A new determination of the (109)Cd half-life was made by a time series of measurements of an aqueous sample using a re-entrant type ionisation chamber. The measurement campaign covered a period of 6 years or approximately 4.7 half-lives of (109)Cd. The resulting value of 462.1 (3) days is in good agreement with the recently published values of 462.29 (30) days and 462.3 (8) days. This new half-life determination will allow evaluators to specify a recommended value of the (109)Cd half-life making it more accurate and precise.

Direct measurement of the half-life of (223)Ra.

Radioactive decay half-life measurements of (223)Ra, a member of the (235)U naturally occurring radioactive decay series, have been performed of a radiochemically pure solution with an ionisation chamber. The radioactive decay of (223)Ra was followed for 50 days, approximately 4.4 half-lives. The deduced half-life of (223)Ra was found to be 11.4358 (28) days, supporting the other published direct measurements. A detailed uncertainty budget is presented. A new evaluation of the published half-life values was performed, indicating significant variation across the existing published values, suggesting that further measurements of the half-life of (223)Ra are required. A new evaluated half-life has been calculated using a power moderated weighted mean of selected experimental values, with a new value of the recommended half-life for (223)Ra of 11.4354 (17) days.

Applying best interests to persistent vegetative state--a principled distortion?

"Best interests" is widely accepted as the appropriate foundation principle for medico-legal decisions concerning treatment withdrawal from patients in persistent vegetative state (PVS). Its application appears to progress logically from earlier use regarding legally incompetent patients. This author argues, however, that such confidence in the relevance of the principle of best interests to PVS is misplaced, and that current construction in this context is questionable on four specific grounds. Furthermore, it is argued that the resulting legal inconsistency is distorting both the principle itself and, more particularly, individual patient interests.