Palladium-103 for Targeted Auger Electron Therapy: From Cyclotron Production and Innovative Separation to In Vivo Generator Evaluation and Preclinical Imaging

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dc.contributor.advisorSzűcs, Zoltán
dc.contributor.authorLaouameria, Aicha Nour
dc.contributor.authorvariantLaouameria, Aicha Nour
dc.contributor.departmentKémiai tudományok doktori iskolahu
dc.contributor.submitterdepTermészettudományi és Technológiai Kar::Kémiai Intézet::Alkalmazott Kémiai Tanszék
dc.date.accessioned2026-03-02T13:39:53Z
dc.date.available2026-03-02T13:39:53Z
dc.date.defended2026-04-30
dc.date.issued19-01-2026
dc.description.abstractPalladium-103 (¹⁰³Pd) is an Auger electron–emitting radionuclide with favorable radiophysical properties for highly localized energy deposition, making it a promising candidate for targeted radionuclide therapy. However, its broader application has been limited by challenges related to production, radiochemical separation, and in vivo validation. This study aimed to develop a complete and integrated workflow for the cyclotron production, separation, recovery, purification, radiolabeling, and preclinical evaluation of ¹⁰³Pd as a theranostic radionuclide. ¹⁰³Pd was produced via the ¹⁰³Rh(p,n)¹⁰³Pd nuclear reaction using optimized irradiation conditions. A diffusion-driven dry-distillation approach was developed for radionuclide separation, exploiting the differences in vapor pressure and diffusion behavior between palladium and rhodium at elevated temperatures. A dedicated radionuclide separation equipment (RSE) enabled selective volatilization and recovery of ¹⁰³Pd under high-vacuum conditions, providing an efficient alternative to conventional wet-chemical methods. Recovery and purification were achieved using an optimized acid-based extraction and anion-exchange chromatography. Experimental studies on palladium diffusion in rhodium supported the separation mechanism, while ICP-MS measurements demonstrated that thermal pre-treatment of rhodium foils significantly reduced residual palladium content, leading to improved specific activity of the produced radionuclide. The optimized RSE achieved separation efficiencies of 64–86% and recovery yields of 81–94%, with high chemical purity confirmed by surface analysis. Radiolabeling of ¹⁰³Pd with clinically relevant chelators (NOTA and DOTA-TATE) resulted in radiochemical purity exceeding 95%. The release of the daughter radionuclide ¹⁰³ᵐRh from [¹⁰³Pd]Pd–DOTA-TOC complexes was experimentally evaluated, with measured release fractions of 10.5 ± 2.7% and 12.0 ± 0.5%, indicating limited daughter release and favorable retention within the complex. Preclinical evaluation using SPECT/CT imaging in murine models demonstrated stable biodistribution and in vivo stability of [¹⁰³Pd]Pd-labeled constructs. Furthermore, a preliminary translational study in a spontaneous canine tumor model showed tumor localization and early indications of therapeutic response. Overall, this work establishes an integrated production-to-preclinical evaluation pipeline for ¹⁰³Pd and demonstrates its feasibility as a theranostic Auger electron–emitting radionuclide, highlighting its potential for highly localized targeted radionuclide therapy.
dc.format.extent116
dc.identifier.urihttps://hdl.handle.net/2437/405240
dc.language.isoen
dc.subjectPalladium-103; Auger electron emitter; Rhodium-103m; Targeted radionuclide therapy; Dry distillation; Radionuclide separation; NOTA; DOTA-TATE; SPECT/CT imaging; In vivo evaluation; Theranostics
dc.subject.disciplineKémiai tudományokhu
dc.subject.sciencefieldTermészettudományokhu
dc.titlePalladium-103 for Targeted Auger Electron Therapy: From Cyclotron Production and Innovative Separation to In Vivo Generator Evaluation and Preclinical Imaging
dc.title.translatedPalladium-103 for Targeted Auger Electron Therapy: From Cyclotron Production and Innovative Separation to In Vivo Generator Evaluation and Preclinical Imaging
dc.typePhD, doktori értekezéshu
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