Ac-EAZY! Towards GMP-Compliant Module Syntheses of ²²⁵Ac-Labeled Peptides for Clinical Application.

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Medical Physics

Background:

• Peptide receptor radionuclide therapy (PRRT) traditionally uses beta-emitters like ⁹⁰Y, ¹⁷⁷Lu, or ¹⁸⁸Re.
• Actinium-225 (²²⁵Ac) offers advantages as an alpha-emitter, including a shorter range and higher linear energy transfer, leading to more precise tumor targeting.
• Limited availability of ²²⁵Ac has hindered its widespread clinical application.

Purpose of the Study:

• To develop and evaluate automated synthesis methods for ²²⁵Ac-labeled peptides.
• To demonstrate the feasibility of producing high-quality ²²⁵Ac-labeled peptides for clinical use.
• To address the challenge of ²²⁵Ac availability through efficient production and purification.

Main Methods:

• Utilized two distinct automated synthesis setups with varied purification systems.
• Employed the Modular-Lab EAZY, a GMP-compliant system, for automated radiolabeling.
• Synthesized masterbatches of ²²⁵Ac-labeled DOTA-TATE and PSMA-I&T.

Main Results:

• Achieved final radiochemical yields of 80-90% for ²²⁵Ac-labeled peptides.
• Demonstrated that DOTA-conjugated peptides can be effectively labeled with ²²⁵Ac.
• Confirmed fulfillment of all quality criteria for the synthesized radiopharmaceuticals.
• Minimized waste generation through the use of small synthesis cassettes.

Conclusions:

• Automated synthesis platforms like the Modular-Lab EAZY are crucial for overcoming ²²⁵Ac availability barriers.
• ²²⁵Ac-based PRRT offers significant benefits, including reduced radiation dose to patients and healthcare personnel.
• Feasible and reproducible patient doses of ²²⁵Ac-labeled peptides can be achieved through optimized automated synthesis.