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

Abstract

Radionuclides emitting Auger electrons (AEs) with low (0.02–50 keV) energy, short (0.0007–40 µm) range, and high (1–10 keV/µm) linear energy transfer may have an important role in the targeted radionuclide therapy of metastatic and disseminated disease. Erbium-165 is a pure AE-emitting radionuclide that is chemically matched to clinical therapeutic radionuclide ¹⁷⁷Lu, making it a useful tool for fundamental studies on the biological effects of AEs. This work develops new biomedical cyclotron irradiation and radiochemical isolation methods to produce ¹⁶⁵Er suitable for targeted radionuclide therapeutic studies and characterizes a new such agent targeting prostate-specific membrane antigen. Biomedical cyclotrons proton-irradiated spot-welded Ho_(m) targets to produce ¹⁶⁵Er, which was isolated via cation exchange chromatography (AG 50W-X8, 200–400 mesh, 20 mL) using alpha-hydroxyisobutyrate (70 mM, pH 4.7) followed by LN2 (20–50 µm, 1.3 mL) and bDGA (50–100 µm, 0.2 mL) extraction chromatography. The purified ¹⁶⁵Er was radiolabeled with standard radiometal chelators and used to produce and characterize a new AE-emitting radiopharmaceutical, [¹⁶⁵Er]PSMA-617. Irradiation of 80–180 mg ^natHo targets with 40 µA of 11–12.5 MeV protons produced ¹⁶⁵Er at 20–30 MBq·µA^–1·h^–1. The 4.9 ± 0.7 h radiochemical isolation yielded ¹⁶⁵Er in 0.01 M HCl (400 µL) with decay-corrected (DC) yield of 64 ± 2% andmore » a Ho/¹⁶⁵Er separation factor of (2.8 ± 1.1) · 10⁵. Radiolabeling experiments synthesized [¹⁶⁵Er]PSMA-617 at DC molar activities of 37–130 GBq·µmol^–1. A 2 h biomedical cyclotron irradiation and 5 h radiochemical separation produced GBq-scale ¹⁶⁵Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutics. This will enable fundamental radiation biology experiments of pure AE-emitting therapeutic radiopharmaceuticals such as [¹⁶⁵Er]PSMA-617, which will be used to understand the impact of AEs in PSMA-targeted radionuclide therapy of prostate cancer.« less

Authors:

Da Silva, Isidro ;

• Search DOE PAGES for author "Da Silva, Isidro"
• Search DOE PAGES for ORCID "0000-0003-3240-5873"

Johnson, Taylor R.; Mixdorf, Jason C.; Aluicio-Sarduy, Eduardo ;

• Search DOE PAGES for author "Aluicio-Sarduy, Eduardo"
• Search DOE PAGES for ORCID "0000-0002-7889-9162"

Barnhart, Todd E.; Nickles, R. Jerome; Engle, Jonathan W. ;

• Search DOE PAGES for author "Engle, Jonathan W."
• Search DOE PAGES for ORCID "0000-0002-3399-7228"

Ellison, Paul A.

• Search DOE PAGES for author "Ellison, Paul A."
• Search DOE PAGES for ORCID "0000-0002-8379-7419"

Publication Date:

Sat Dec 11 00:00:00 EST 2021

Research Org.:

Univ. of Wisconsin, Madison, WI (United States)

Sponsoring Org.:

USDOE Office of Science (SC)

OSTI Identifier:

1835451

Alternate Identifier(s):

OSTI ID: 1864555

Grant/Contract Number:  

SC0020955

Resource Type:

Published Article

Journal Name:

Molecules

Additional Journal Information:

Journal Name: Molecules Journal Volume: 26 Journal Issue: 24; Journal ID: ISSN 1420-3049

Publisher:

MDPI AG

Country of Publication:

Switzerland

Language:

English

Subject:

62 RADIOLOGY AND NUCLEAR MEDICINE; Targeted radionuclide therapy; Auger emission; radionuclide production; lanthanide separation; erbium-165; 165Er