¹³⁵La as an Auger-electron emitter for targeted internal radiotherapy

Abstract

<b>Introduction:</b> <sup>135</sup>La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, imaging characteristics, and dosimetry related to <sup>135</sup>La therapy.
 <b>Methods and Results:</b> <sup>135</sup>La was produced by 16.5 MeV proton irradiation of metallic <sup>nat</sup>Ba on a medical cyclotron, and was isolated and purified by trap-and-release on weak cation-exchange resin. The average production rate was 407 ± 19 MBq/µA (saturation activity, n = 3), and the radionuclidic purity was 98% at 20 h post irradiation. Chemical separation recovered > 98 % of the <sup>135</sup>La with an effective molar activity of 70 ±20 GBq/µmol. To better assess cellular and organ dosimetry of this nuclide, we have recalculated the X-ray and Auger emission spectra using a Monte Carlo model accounting for effects of multiple vacancies during the Auger cascade. The generated Auger spectrum was used to recalculate cellular S-factors. 
 <b>Conclusion:</b> <sup>135</sup>La was produced with high specific activity, reactivity, radionuclidic purity, and yield. The emission spectrum and the dosimetry are favorable for internal radionuclide therapy.&#13.

Production and in vivo PET/CT imaging of the theranostic pair 132/135La

“…Due to the low affinity of the DGA resin for La 3+ in 0.1 M HCl, 132/135 La 3+ was eluted in a small volume (<600 µL), with a final recovery efficiency of 92 ± 2% (n = 6) and a Ba/La separation factor of 10 6 . This separation factor is four orders of magnitude higher than those reported in previous separation strategies 3 . Figure 2 summarizes the separation strategy and the elution profile from the branched DGA column.

Figure 2( A ) Simplified separation strategy, ( B ) Elution profile from the branched - DGA resin as measured by MP-AES (Ba, Zn, Fe, and Cu) and HPGe ( 132/135 La).

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“…Due to the natural isotopic composition of the target, short-lived 134 La and 136 La were co-produced but at the end of chemistry (EOC) (ca. 5 h post-EOB), had decayed below the detection limit 3 . Relatively longer-lived 132 La was also co-produced with a yield of 0.26 ± 0.05 MBq μAh −1 (~5% relative to 135 La activity at EOB).…”

“…Furthermore, small quantities of co-produced, positron-emitting 132 La enable seamless implementation of a theranostic approach and the noninvasive interrogation of pharmacokinetic profiles by in vivo positron emission tomography imaging and ex vivo biodistribution. To date, relatively few separation strategies have been reported for the radiochemical isolation of no-carrier-added lanthanum from barium, and they have achieved only moderate separation factors and chemical purity 3–5 . Our goal was to develop an optimized production method for 132/135 La with a chemical purity suitable for chelation and in vivo PET imaging of radiolabeled, targeted theranostic pharmaceuticals.

Figure 1Simplified decay schemes of 132 La ( A ) and 135 La ( B ) 4,15,16 .

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Half-lives of La132 and La135

“…In the process of investigating this radionuclide pair [4], we discovered that not only are the evaluated half-lives relatively imprecise compared with other nuclear data, but they are also inaccurate. Previously measured half-lives for 135 La are shown in Table I where the Nuclear Data Sheets (NDS) value is a weighted average of the first and second half-lives listed.…”

High yield cyclotron production of a novel 133/135La theranostic pair for nuclear medicine

“…High LET Auger electron emissions have achieved encouraging clinical results, with 111 In-DTPA-octreotide and 125 I-IUdR causing tumor remissions in patients with lower normal tissue toxicity, and improvements in the survival of glioblastoma patients using 125 I-mAb 425 with minimal normal tissue toxicity 4 . A recently developed theranostic pair is 132/135 La, where positron emissions from 132 La are used for PET imaging while the Auger electrons from 135 La have the potential for use in Auger electron therapy (AET) [5][6][7] . Theranostic La pairs are not only inherently useful but also can serve as surrogates for potential future study relating to 225 Ac alpha-particle therapy.…”