Separation of 44Sc from 44Ti in the Context of A Generator System for Radiopharmaceutical Purposes with the Example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T Synthesis.

Anton A Larenkov,Vladimir N Iatsenko,Artur G Makichyan

doi:10.3390/molecules26216371

Anton A Larenkov, Vladimir N Iatsenko + Show 1 more

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https://doi.org/10.3390/molecules26216371

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Abstract

Today, 44Sc is an attractive radionuclide for molecular imaging with PET. In this work, we evaluated a 44Ti/44Sc radionuclide generator based on TEVA resin as a source of 44Sc. The generator prototype (5 MBq) exhibits high 44Ti retention and stable yield of 44Sc (91 ± 6 %) in 1 mL of eluate (20 bed volumes, eluent—0.1 M oxalic acid/0.2 M HCl) during one year of monitoring (more than 120 elutions). The breakthrough of 44Ti did not exceed 1.5 × 10−5% (average value was 6.5 × 10−6%). Post-processing of the eluate for further use in radiopharmaceutical synthesis was proposed. The post-processing procedure using a combination of Presep® PolyChelate and TK221 resins made it possible to obtain 44Sc-radioconjugates with high labeling yield (≥95%) while using small precursor amounts (5 nmol). The proposed method takes no more than 15 min and provides ≥90% yield relative to the 44Sc activity eluted from the generator. The labeling efficiency was demonstrated on the example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T synthesis. Some superiority of PSMA-I&T over PSMA-617 in terms of 44Sc labeling efficiency was demonstrated (likely due to presence of DOTAGA chelator in the precursor structure). It was also shown that microwave heating of the reaction mixture considerably shortened the reaction time and improved radiolabeling yield and reproducibility of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T synthesis.

Highlights

The advantages of nuclear medicine methods have led to its sustainable development over the past few decades and its transformation into an integral part of clinical practice in developed countries
Two generator columns (PEEK 100 mm × Ø2.1 mm, 150 mg of TEVA resin) with an initial load of 0.5 and 5.0 MBq 44 Ti were prepared for this study and used throughout the work
This work was started with one tentative experiment as proof-of-concept for Greene’s method [17] with 0.1 M H2 C2 O4 /0.2 M HCl as eluent but with TEVA resin instead of Dowex 1 × 8 as sorbent

Summary

Introduction

The advantages of nuclear medicine methods have led to its sustainable development over the past few decades and its transformation into an integral part of clinical practice in developed countries. The results of clinical applications of [44 Sc]Sc-DOTATOC [3] for the diagnosis of neuroendocrine tumors, as well as [44 Sc]Sc-PSMA-617 [9,10] for the diagnosis of prostate cancer have been published. It is hypothesized, that the clinical application of 44 Sc may be compromised by the high dose exposure caused by the co-emission of 1157 keV γ-rays (99.9%) [11]. These concerns of radiation safety may be addressed by using tungsten-based containers that are employed for other commercial PET nuclides with high energy γ-emission

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