Skipping Purification Steps May Not Compromise Radiopharmaceutical Quality, Study Finds

Radioligand therapy depends on the reliable production of radioactive drugs, and a new study asks a deceptively simple question about that process: is the purification step actually necessary? Researchers compared two automated production workflows for three radiopharmaceuticals used in nuclear medicine, one prepared with C-18 solid phase extraction (SPE) purification and one without, and found that omitting purification did not significantly change the quality of the final products in their setting.

The work, published in EJNMMI Radiopharmacy and Chemistry as an open access research article, focused on three compounds: [177Lu]Lu-PSMA I&T, [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TOC. All three were produced and formulated using single-use cassette approaches on Eckert & Ziegler’s Modular-Lab PharmTracer synthesis module.

To evaluate the two production methods, the team drew on quality control data from 20 to 30 batches for each radiopharmaceutical. The analytical toolkit included reversed-phase high-performance liquid chromatography (RP-HPLC), instant thin-layer chromatography (iTLC) and gas chromatography (GC) analyses, covering the key parameters that determine whether a batch can be released for use.

The headline result is reassuring for streamlined production. Radiochemical purity measured by RP-HPLC showed no significant variations between the two production procedures. All batches analysed conformed to pharmacopeial and internal specifications for product release, regardless of whether SPE purification had been performed.

That said, the comparison was not without nuance. Significant differences between the product formulations did emerge in two areas: the amounts of unbound radiometal species and the ethanol concentrations. These are formulation-level distinctions rather than failures of specification, but they illustrate that the two workflows do not produce identical products in every respect, even when both meet release criteria.

During solid phase extraction purification of [177Lu]Lu-PSMA I&T, the researchers noticed a slight increase in the formation of a radiolytic side product. This detail matters because radiolytic impurities are a known consideration in the handling of highly radioactive therapeutic formulations, and the finding suggests purification itself can introduce or concentrate such by-products in at least some circumstances.

Taken together, the authors conclude that in their setting, omitting product purification from automated radiopharmaceutical production did not lead to any significant changes in the quality of the final products for all three radiotracers evaluated. On that basis, they argue that their data indicate product purification is not required in all production procedures involving the preparation of radiopharmaceuticals for radioligand therapy.

However, the researchers are careful not to overgeneralise. They emphasise that the decision to skip purification must be based on a case-by-case evaluation for each synthesis module and each radiopharmaceutical in question. The findings apply to the specific equipment, peptides and radionuclides tested, and other laboratories using different modules or formulations would need to generate their own batch data before drawing similar conclusions.

The study arrives amid a growing body of quality control literature on lutetium-177-labelled radiopharmaceuticals, with related open access work on improved quality control of [177Lu]Lu-PSMA I&T, on the effects of radiolysis on the in vivo biodistribution of that compound, and on long-term quality control of manually prepared lutetium-177-labelled radiopharmaceuticals in routine clinical practice. Within that landscape, this comparative analysis offers production laboratories a data-driven starting point for deciding when a purification step can be safely left out of an automated synthesis.

Subject of Research: Automated radiolabelling of PSMA I&T and somatostatin analogues with lutetium-177 and yttrium-90, with and without solid phase extraction purification

Article Title: Comparative radiolabelling of PSMA I&T and somatostatin analogues with ¹⁷⁷Lu and ⁹⁰Y: the impact of SPE purification

Article References: Kraihammer, M., Decristoforo, C., Knoll, A., Zavvar, T. S., von Guggenberg, E., Rangger, C., Haubner, R., & Sporer, E. (2026). Comparative radiolabelling of PSMA I&T and somatostatin analogues with ¹⁷⁷Lu and ⁹⁰Y: the impact of SPE purification. EJNMMI Radiopharmacy and Chemistry. https://doi.org/10.1186/s41181-026-00496-2

Image Credits: AI Generated

DOI: 10.1186/s41181-026-00496-2

Keywords: radiopharmaceuticals, lutetium-177, yttrium-90, PSMA I&T, DOTA-TATE, DOTA-TOC, solid phase extraction, quality control, radioligand therapy, automated synthesis, EJNMMI Radiopharmacy and Chemistry, peptide radiolabelling