LARAMED

APHRODITE-155 PRIN PNRR 2022 (2024-2026) Project completed – February 28, 2026

APHRODITE-155 is the acronym of “Accelerator-based Production of tHeranostic radionuclides: Investigations on TErbium-155” funded as PRIN PNRR 2022 for the years 2024-2026 (“Finanziato dall’Unione europea – Next Generation EU” Mission 4, Component 2, Investment 1.1). The project has involved a national collaboration between INFN, University of Ferrara (UNIFE), and University of Milan (UNIMI) and has been successfully completed, achieving all its scientific and technological objectives also thanks to the collaboration with the Sacro Cuore Don Calabria Hospital (Negrar, VR), the Istituto Oncologico Veneto (IOV, PD), the GIP ARRONAX facility and the Physics Departments of Padova and Pavia Universities.

Project overview

Terbium radionuclides are gaining increasing attention in nuclear medicine due to their unique ability to combine diagnostic imaging and targeted therapy within the same chemical family. In particular, terbium offers a full set of medically relevant isotopes, including α-, β⁻-, β⁺-, and γ-emitters, making it especially attractive for theranostic applications. Within this family, ¹⁵⁵Tb is a promising radionuclide for SPECT imaging, thanks to its suitable gamma emissions and relatively long half-life (about 5.3 days), which allows extended imaging protocols and accurate biodistribution studies.

Main decay characteristics of 155Tb 


 Main decay characteristics of 155Tb 

Despite its potential, the widespread use of ¹⁵⁵Tb is still limited by the complexity of its production and the lack of reliable and scalable supply routes. In particular, achieving high radionuclidic purity while maintaining sufficient production yield represents a major challenge, especially when using cyclotron-based methods.

The APHRODITE-155 project was conceived to address these limitations by systematically investigating and comparing two complementary production strategies based on proton-induced reactions. The first approach is a direct production route, relying on the irradiation of enriched ¹⁵⁵Gd targets with low-energy proton beams available at medical cyclotrons. The second approach is an indirect route, based on the production of ¹⁵⁵Dy via irradiation of natural ¹⁵⁹Tb at medium- to high-energy cyclotrons, followed by its decay to ¹⁵⁵Tb in a generator-like scheme.

A key objective of the project was not only to demonstrate the feasibility of these production routes, but also to provide a quantitative comparison in terms of production yield, radionuclidic purity, and suitability for medical applications. To this end, the project combined experimental activities with advanced modelling and dosimetric evaluations, enabling a comprehensive understanding of the factors governing the production and quality of ¹⁵⁵Tb.

The work covered the entire production chain, including the development of solid targets, irradiation campaigns, radiochemical separation processes, and quality control through gamma spectrometry. By integrating these elements, APHRODITE-155 aimed to establish a reliable framework for the future implementation of ¹⁵⁵Tb production and its use in preclinical and clinical studies.

Main results

The project delivered significant scientific and technological outcomes:

  • development of solid target manufacturing techniques for Gd₂O₃ and Tb₂O₃ using Spark Plasma Sintering;
  • implementation of optimized radiochemical separation protocols (Tb/Gd and Tb/Dy/Tb);
  • experimental validation of ¹⁵⁵Tb production using both medical and research cyclotrons;
  • identification of optimal irradiation and processing parameters;
  • definition of radionuclidic purity requirements for medical applications, supported by dosimetric analysis.

A major achievement of the project was the first demonstration in Italy of the complete production of ¹⁵⁵Tb using a medical cyclotron.
The results of the project clearly indicate that the direct and indirect production routes should not be considered as alternatives, but rather as complementary strategies. The direct route offers simplicity, shorter production times, and compatibility with widely available medical cyclotrons, while the indirect route provides access to higher yields and potentially higher radionuclidic purity, albeit with increased complexity and infrastructure requirements.
The choice of the most suitable approach therefore depends on several factors, including available facilities, target material, required activity levels, and the intended clinical application.

Impact and future perspectives

The APHRODITE-155 project provides a solid scientific and technological basis for the future implementation of ¹⁵⁵Tb production in Italy. The developed methodologies enable the transition from experimental validation to routine production, particularly for preclinical applications, and represent a key step toward clinical translation.

From a broader perspective, the project contributes to the development of a national capability in the production of innovative medical radionuclides, strengthening Italy’s role within the European nuclear medicine landscape. By supporting the availability of ¹⁵⁵Tb and related isotopes, APHRODITE-155 opens new opportunities for the advancement of personalized theranostic approaches and for future clinical applications.

Main publications

The scientific results of the project have been disseminated through several open-access publications, including studies on target manufacturing, nuclear data, and production optimization. Among these:  

Additional publications summarizing the final results are in preparation.