First Steps at the Cyclotron of Orléans in the Radiochemistry of Radiometals: 52Mn and 165Er

Abstract

This work describes the first real developments in radiochemistry around exotic radionuclides at the cyclotron of Orléans focusing on the radiochemistry of two radiometals 165 Er and 52 Mn. For these developments, targets were irradiated during 0.5-2 h at a maximum current of 2 µA. All activities have been determined by radiotracer method. The production of 165 Er from a natural Ho target that was irradiated is described. Higher activities of 165 Er were obtained via deuteron irradiation then proton with lower ratio 165 Er/ 166 Ho (400/1 to 8/1). By using LN2 resin, the separation of adjacent lanthanides was made on various concentrations of HNO 3 (0.3 to 5 M). Weight coefficients (Dw) were defined in a batch test. Then, the first tests of separation on a semi-automated system were made: the ratio 166+nat Ho/ 165 Er in an isolated fraction was significantly reduced (1294 ± 1183 (n = 3)) but the reliability and reproducibility of the system must be improved. Then, a new Cr powder-based target for 52 Mn production was designed. Its physical aspects such as mechanics, thermal resistance and porosity have been studied. Dw for various compositions of eluent Ethanol/HCl were evaluated by reducing contact time (1 h) comparative to the literature. A first evaluation of semi-automated separation Cr/Mn has been made.Instruments 2018, 2, 15 2 of 23 cyclotron of Orléans is of interest in producing radionuclides for analytical applications allowing for the validation of the separation by the radiotracer method [9] and a method as sensitive as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In this context, it was necessary to initiate tools and methodology in radiochemistry to develop further the accelerator in the area of medical radionuclides. However, two constraints relative to the choice of radionuclides were met at the cyclotron of Orléans. The first constraint was to produce gamma emission and the second was that the half-life of the radionuclide produced must be below 100 days (due to nuclear waste management considerations). Hence for the following work, we used 165 Er/Er, 166 Ho/Ho, 51 Cr/Cr and 52 Mn/Mn. Other tools to improve radiochemical separation based on resins, methodology, and target design must be developed. Two cases hereafter illustrate the method's development for the production and subsequent separation of 165 Er and 52 Mn.Instruments 2018, 3, 15 2 of 22 radionuclides for analytical applications allowing for the validation of the separation by the radiotracer method [9] and a method as sensitive as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In this context, it was necessary to initiate tools and methodology in radiochemistry to develop further the accelerator in the area of medical radionuclides. However, two constraints relative to the choice of radionuclides were met at the cyclotron of Orléans. The first constraint was to produce gamma emission and the second was that the half-life of the radionuclide produced must be below 100 days (due to nuclear waste management considerations)...

Cutting edge rare earth radiometals: prospects for cancer theranostics

“…There have been a number of nuclear reaction routes reported for the production of 165 Er, typically using protons, deuterons or neutrons as the bombardment particles with either natural or enriched Er targets, or natural Ho targets (100% natural abundance of 165 Ho) (Sadeghi et al 2010 ; Zandi et al 2013 ; Beyer et al 2004b ; Tárkányi et al 2007 , 2008a , b , c , 2009 ; Hermanne et al 2013 ). The use of natural Er targets utilises the generator approach to produce ingrown 165 Er after the β − -decay of 165 Tm produced via either the nat Er(p,xn) 165 Tm → 165 Er or the nat Er(d,xn) 165 Tm → 165 Er nuclear reactions, giving the resultant 165 Er in no-carrier-added form after separation from the target material (Tárkányi et al 2007 ; Vaudon et al 2018 ). These charged particle bombardment approaches on natural Er have resulted in the production of reasonably long-lived 167 Tm (t 1/2 = 9.25 d) and 168 Tm (t 1/2 = 93.1 d) impurities, and the natural abundance of the main contributing 166 Er isotope being only ~ 33.5% has led to enriched 166 Er targets being preferred (Vaudon et al 2018 ).…”

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

“…The second step utilized EXC with a commercially available HEHEHP-impregnated resin (LN2, 20-50 µm, Triskem Int., Bruz, France) [37], based on previous literature work on its use for Ho/Er separations [41]. Fritted polypropylene columns (5.5 mm diameter, 1 mL, Supelco Inc., Bellefonte, PA, USA) were dry-packed with resin (500 mg) and preconditioned with 1 M HNO 3 (5 mL) followed by 0.1 M HNO 3 (25 mL).…”

“…Following the CX/αHIB column, the acidified Ho/ 165 Er solution was loaded onto the LN2 column, trapping both 165 Er and Ho. Based on previously published studies [41], the column was rinsed with 0.4 M HNO 3 to affect the differential elution of holmium before erbium. As shown in Figure 3, elution with 0.4 M HNO 3 (50 mL) removed >99% of the holmium, along with a cumulated ~20% of the 165 Er.…”

“…Radiochemical separations of adjacent lanthanides have traditionally been performed using cation exchange (CX) chromatography with the complexing agent α-hydroxy isobutyrate (αHIB) [29,30], with recent reports effectively separating Gd/Tb [31,32], Dy/Ho [33], Ho/Er [22,24], and Er/Tm [34,35]. Additionally, extraction chromatography (EXC) resins [36,37] impregnated with acidic organophosphorous extractants including bis(2-ethylhexyl) phosphoric acid (HDEHP, LN resin) [38,39], 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (HEHEHP, LN2 resin) [40][41][42][43], and bis(2,4,4-trimethyl-1-pentyl)phosphinic acid (H[TMPeP], LN3 resin) [24,43] have been used to separate adjacent heavy lanthanides.…”

Special Issue ”Instruments and Methods for Cyclotron Produced Radioisotopes”

“…The measurement of the cross-sections is a complex process and the possibility to derive them from Thick Target Yield (TTY) measurements in the case of scandium was studied by M. Sitarz et al [19]. Other radio-metals of interest are 52 Mn and 165 Er studied in Orleans [20] and 45 Ti, which was proposed for PET, as reported in the review by P. Costa et al [21].…”