A High Separation Factor for ¹⁶⁵Er from Ho for Targeted Radionuclide Therapy

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Oncology

Background:

• Auger electron (AE) emitting radionuclides offer potential for targeted radionuclide therapy due to their high linear energy transfer and short range.
• Erbium-165 (Er-165) is a pure AE emitter, chemically similar to 177Lu, making it valuable for studying AE biological effects.
• New production and isolation methods for Er-165 are needed for targeted radionuclide therapeutic studies, particularly for agents targeting prostate-specific membrane antigen (PSMA).

Purpose of the Study:

• To develop novel biomedical cyclotron irradiation and radiochemical isolation techniques for producing Er-165.
• To characterize a new AE-emitting radiopharmaceutical, [Er-165]PSMA-617, for PSMA-targeted therapy.
• To enable fundamental radiation biology experiments on pure AE-emitting radiopharmaceuticals.

Main Methods:

• Proton irradiation of holmium (Ho) targets using biomedical cyclotrons to produce Er-165.
• Isolation of Er-165 via cation exchange and extraction chromatography.
• Radiolabeling of purified Er-165 with chelators to synthesize [Er-165]PSMA-617.

Main Results:

• Production of Er-165 achieved at 20-30 MBq·µA−1·h−1 via proton irradiation of Ho targets.
• High decay-corrected yield (64 ± 2%) and Ho/Er-165 separation factor ((2.8 ± 1.1) · 10^5) obtained through radiochemical isolation.
• Synthesis of [Er-165]PSMA-617 at high molar activities (37-130 GBq·µmol−1) suitable for therapeutic studies.

Conclusions:

• GBq-scale Er-165 production is feasible with optimized cyclotron irradiation and radiochemical separation.
• The developed methods yield Er-165 with satisfactory molar activities for radiopharmaceutical production.
• This work facilitates fundamental research into AE dosimetry and the efficacy of AE-emitting agents like [Er-165]PSMA-617 in PSMA-targeted prostate cancer therapy.