Introduction: Auger electron-emitting radionuclides
with low (0.001–1 keV) energy, short-range (2–500 nm),
and high linear energy transfer (4–26 keV/μm) can play
an important role in the targeted radionuclide therapy (TRT) of cancer. 165Er is a pure Auger electron-emitting radionuclide, making
it a useful tool for the fundamental studies of the biological effects
of Auger electrons. This work develops a simple, inexpensive, high
separation factor, and high molar activity radiochemical isolation
process for the production of 165Er (t1/2 10.36 h) suitable for TRT in vitro and in vivo studies
using irradiated natHo solid targets. Methods: Small medical cyclotron proton-irradiation of natHo
targets produced 165Er in GBq scale quantities. 165Er was isolated using cation exchange chromatographic resin (AG 50W-X8,
200–400 mesh, 20 mL, under atmospheric pressure) using α-hydroxyisobutyric
acid (70 mM, pH 4.75) followed by extraction using TK212, TK211, and
TK221 extraction chromatographic columns. Radio nuclidic and chemical
purity of the final 165Er were confirmed using HPGe Gamma
spectrometry and induction coupled plasma–mass spectrometry
analysis, respectively. The purified 165Er was radiolabeled
with two radiometal chelators (DOTA and Crown) and used to produce
a new Auger electron-emitting radiopharmaceutical, [165Er]Er-Crown-TATE. Results: Irradiation of 200 mg natHo targets with 20–30 μA of 12.8 MeV protons
produced 165Er at 25 ± 5 MBq·μA–1·h–1. The 4.5 ± 0.5 h radiochemical isolation
yielded GBq scale of 165Er in 0.05 M HCl (2 mL) with a
radiochemical yield of 78.0 ± 5.6% decay corrected to the end
of bombardment (EoB) and a Ho/165Er separation factor of
(1.14 ± 0.25) × 106. The product showed high
radio nuclidic purity and chemical purity. Concentration-dependent
radiolabeling experiments with Crown and DOTA were performed resulting
in the successful labeling of 165Er with high (>90%)
radiochemical
yield. Radiolabeling experiments with Crown-TATE were performed 8
h after EoB and synthesized [165Er]Er-Crown-TATE at molar
activities of 202.4 MBq·nmol–1 at the end of
synthesis (EoS). Conclusions: A 3 h cyclotron irradiation
and 4.5 h radiochemical separation produced GBq-scale 165Er suitable for producing radiopharmaceuticals at molar activities
satisfactory for investigations of targeted radionuclide therapeutic
effects of Auger electron emissions. This will enable future fundamental
radiation biology experiments of pure Auger electron-emitting therapeutic
radiopharmaceuticals, such as [165Er]Er-Crown-TATE, which
will be used to understand the impact of Auger electrons in TRT.