Theranostic radiopharmaceuticals are molecules that can safely carry radioactive isotopes inside targeted human tissues and help physicians get accurate images of tumours, allowing them to more effectively and precisely eliminate cancer cells. This branch of pharmaceuticals has attracted enormous interest in the last decade and several radiopharmaceuticals have been developed based on radionuclides such as Gallium-68 (Ga-68). In recent years Ga-68 radiopharmaceuticals have been used increasingly in clinical applications for cancer diagnostics and using Ge-68/Ga-68 generators. However, despite its usefulness, there are supply challenges related to this important isotope.
The IAEA supports international efforts in the production and application of theranostic radiopharmaceuticals, and is launching a new Coordinated Research Project (CRP) focusing on direct cyclotron production of [68Ga]GaCl3 and related radiopharmaceuticals. The CRP aims to aid and share international experience on production and quality control of Ga-68 using the 68Zn(p,n)68Ga route. It will also focus on radiopharmaceutical production, quality control, quality assurance and regulatory aspects for their ultimate use in clinical applications.
Ga-68 has played a remarkable role in clinical research worldwide, particularly in routine clinical studies for oncological applications with Positron Emission Tomography (PET) over the last 20 years. Ga-68 is very well suited as a diagnostic isotope for pairing with therapeutic radiometal isotopes, particularly when targeting molecules that can utilize the same chelator for both Ga-68 and the therapy isotope (for example, Lu-177 and Ac-225).
Currently, the most common method for obtaining Ga-68 is via a Ge-68/Ga-68 generator. Generators are convenient for many applications because the long half-life of the parent nuclide Ge-68 (270.93 days) guarantees an ongoing supply of Ga-68 for up to nine months. The eluted Ga-68, in the form of [68Ga]GaCl3, can be used for labelling and therefore has led to significant advances in Ga-68 chemistry and to the development of targeted PET radiopharmaceuticals. An IAEA CRP on the subject of generator-based Ga-68 radiopharmaceuticals was completed in 2017.
The usable Ga-68 activity from current generators is nevertheless limited by the amount of loaded activity; the minimum interval between two elutions; the maximum number of elutions; the elution efficiency; and the possibility of parent radionuclide breakthrough. Currently, the availability of generators is not enough to meet global demand. IAEA’s publication Gallium-68 Cyclotron Production discusses the alternative direct Ga-68 production in a medical cyclotron via 68Zn(p,n)68Ga route on a small to medium energy cyclotron. Recent responses to this publication and inquiries from radiopharmacists demonstrate that, because of the complex technology involved, experts require more guidance on how to implement this technology.
Due to the large number of existing cyclotron facilities worldwide, cyclotron-based approaches have greatly expand the availability of Ga-68. For such approaches to be successful, existing cyclotron infrastructure and personnel must be prepared for, and adapted to, Ga-68 production through knowledge and expertise exchange with the research-oriented facilities where these approaches were developed. This CRP focuses on building this link.
CRP Overall Objective
To formulate guidelines and exchange expertise between Member States to enable cyclotron-based production of Ga-68 and the preparation of Ga-68 radiopharmaceuticals for preclinical and human use.
Specific Research Objectives
- transfer of technology and expertise for optimal cyclotron production of Ga-68 using solid and/or liquid targets;
- transfer of expertise and methods for the separation and purification of cyclotron-produced [68Ga]GaCl3;
- provide guidance for quality control and quality assurance of cyclotron-produced [68Ga]GaCl3;
- provide radiosynthetic procedures for preparation of widely used Ga-68 radiopharmaceuticals (i.e. somatostatin receptor and PSMA ligands) using cyclotron-produced [68Ga]GaCl3, including quality control tests;
- develop guidance for regulatory approval for the human use of radiopharmaceuticals using cyclotron-produced [68Ga]GaCl3 for investigational and routine clinical applications;
- adapt the methods developed for production of [68Ga]GaCl3 using liquid and solid targets to other radionuclide accessible through this technology.
Criteria
Minimal requirement for facilities to join the CRP, considering the short half-life of Ga-68, are as follows:
- existing operational cyclotron with a proton beam energy greater than 12 MeV;
- a solid target station or a dedicated liquid target system (not in use for routine production of F-18);
- dedicated synthesis module for radiometals.
How to join this CRP
Proposals must be received no later than 31 July 2020. Please submit your Proposal for Research Contract or Agreement by email to the IAEA’s Research Contracts Administration Section, using the appropriate template on the CRA website.
For further information related to this CRP, potential applicants should use the contact form under the CRP page.
