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Saeedi Saghez, Behrad

University of British Columbia

Auger electron-emitting (AEE) 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 (t₁/₂=10.36 h) decays 100% via electron capture and is one of a few pure AEE radionuclides, making it a useful tool for understanding the therapeutic potential of Auger electrons (AE). In addition, ¹⁶⁵Er emits high-intensity, low-energy X-rays with high-intensity that can be used for targeted radionuclide imaging (TRI) of cancer. This work develops a high separation factor radiochemical isolation process for producing ¹⁶⁵Er and establishes ¹⁶⁵Er as a promising single photon emission computed tomography (SPECT) imaging radionuclide. Small medical cyclotron proton-irradiation of ¹⁶⁵Ho targets produced ¹⁶⁵Er in GBq scale quantities. ¹⁶⁵Er was isolated using a sequential combination of cation exchange chromatography (AG 50W-X8) and extraction chromatography (TK212, TK211, and TK221). The purified ¹⁶⁵Er was radiolabeled with two radiometal chelators (DOTA and crown), and the labeling radiochemical yield (RCY) was determined using radio-thin layer chromatography (radio-TLC). The purified ¹⁶⁵Er was used to produce two new AEE radiopharmaceuticals, [¹⁶⁵Er]Er-crown-TATE and [¹⁶⁵Er]Er-PSMA-617, and radio high-Performance liquid chromatography (radio-HPLC) was used to confirm the RCY. The cellular uptake and internalization of [¹⁶⁵Er]Er-crown-TATE in AR42J and [¹⁶⁵Er]Er-PSMA-617 in 22Rv1 cells were studied. The produced ¹⁶⁵Er was used to evaluate the performance of this radionuclide for SPECT imaging using phantoms and in vivo imaging of LNCaP tumor-bearing mice. A 4 h irradiation (13 MeV and 30 μA) and 4.5 h radiochemical separation produced GBq-scale ¹⁶⁵Er at the end of synthesis (EoS). Concentration-dependent radiolabeling with crown and DOTA showed successful labeling of ¹⁶⁵Er with high (>90%) RCY at chelator concentrations as low as 10⁻⁶ M. Dose escalation with crown-TATE and PSMA-617 synthesized [¹⁶⁵Er]Er-crown-TATE and [¹⁶⁵Er]Er-PSMA-617 at high molar activities (>200 MBq/nmol). The cellular uptake and internalization assays of [¹⁶⁵Er]Er-crown-TATE in AR42J and [¹⁶⁵Er]Er-PSMA-617 in 22Rv1 cells showed satisfactory uptake of pharmaceuticals after 2-4 hours of incubation (30-50%). ¹⁶⁵Er was established as a SPECT radionuclide with high resolution and great contrast recovery suitable for cancer TRI.

Text

2024-08-15

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/88946

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/