A Consensus Time for Performing Quality Control of 225Ac-Labeled Radiopharmaceuticals

Background: As 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and analysis. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately calculated. Results: Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP using pre-equilibrium measurements at early time points. The 585 TLC measurements span RCP values of 1.8% to 99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. At 2 h the mean average error is < 3%. A measurement of RCP > 90% at this time point predicts a true RCP > 97%. These findings were independently validated using NaI(Tl) scintillation counting and high resolution gamma spectroscopy on a smaller set of samples with 10% ≤ RCP ≤ 100%. Conclusions: RCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC using various methods of quantifying particle emissions. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.

A Consensus Time for Performing Quality Control of 225Ac-Labeled Radiopharmaceuticals

Background: As 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and analysis. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately calculated.Results: Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP using pre-equilibrium measurements at early time points. The 585 TLC measurements span RCP values of 1.8% to 99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. At 2 h the mean average error is < 3%. A measurement of RCP > 90% at this time point predicts a true RCP > 97%.Conclusions: RCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.

Majority rule dynamics between a double coalition and a third opinion: coalition profit models and majority coalition ties

This article explores the opinion dynamics of a double coalition opinion against a third opinion under majority rule updates on odd fixed size connected groups. For this purpose, coalition benefit criteria and three opinion formation models which extend the 2-state majority rule model on lattices are introduced. The proposed models focus on the coalition profit of its constituent coalition opinions and cover the possible final scenarios from coalition alliance perspective: either minor opinion or major opinion is favored, or dynamics do not favor to any coalition opinion. Opinion exchanges take place on a torus embedded lattice network of a 3-state system having in consideration tie configurations and two rules to break them: either by random choice or leaving ties unaltered. Models were analyzed in the statistical mechanics spirit through Monte Carlo simulations without node replacement. Estimations for coalition benefits, the growth of coalition ties, and consensus probabilities are reported. The loss of coalition strengths due to coalition ties and its indecision is indicated. In particular, the logistic decay of consensus probability is due to the logistic adaptive growth of coalition ties. Scaling behaviors for consensus time and coalition ties in terms of network size are suggested. The results of numerical simulations are discussed in the context of social influence and social dynamics.

Definition of public action resources1

This chapter returns to and explores the resource model in detail. It defines ten public action resources: Force, Law, Personnel, Money, Property, Information, Organization, Consensus, Time, Political Support. It also introduces a new resource-related definition of public action resources (based on the so-called institutional regimes for natural, manufactured, social and human resources as defined by the World Bank) and developed by the author and his colleagues. Finally, it also presents a new definition of the multiple functions of law (covering both institutions and specific public action resources).

Public Policy Resources

Building on Knoepfel’s previous book, Public policy analysis, this book offers a conceptually coherent view of ten public policy resources: force, law, personal, money, property rights, information, organisation, consensus, time and political support. The book demonstrates the interplay of the different resources in a conceptually coherent framework and presents numerous illustrations of ways of mobilising the resources and managing them in a sustainable way, resource exchanges and the role of institutions governing the interrelationships between actors and resources. The book will be valuable to postgraduate students as well as those working in policy programming and implementation across both public and private sectors and in non-governmental organisations.