Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The ⁶⁸Ga/¹⁷⁷Lu-PSMA-1 combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Specifically, ¹⁷⁷Lu-PSMA-1 is used in the treatment of castration-resistant prostate cancer that is ineffective or intolerant to the latest generation of chemotherapy and/or hormone therapy. This radiopharmaceutical is manufactured in a radiopharmaceutical synthesizing unit and must pass a quality control where the radiochemical purity (RCP) is assessed prior to release of the batch. RCP evaluation is performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Since there is no monograph for ¹⁷⁷Lu-PSMA-1 in the European Pharmacopoeia, we validate the analytical methods according to the EANM recommendations adapted from ICH Q2. Specificity, linearity, accuracy, precision, intermediate precision, limit of quantification (LOQ) and robustness were described for HPLC and TLC in this study. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of ¹⁷⁷Lu-PSMA-1.

The increasing use of [⁶⁸Ga]Ga-based radiopharmaceuticals in PET imaging, requires efficient quality control procedures. The standard r-TLC method for verifying [⁶⁸Ga]Ga-EDOTREOTIDE (Somakit-TOC®) radiochemical purity (RCP) is time-consuming, creating workflow challenges in radiopharmacies. This study evaluates an optimized r-TLC method with a reduced migration distance (4 cm vs. 9 cm) to improve efficiency while maintaining analytical reliability. Tests for specificity, accuracy and robustness were performed using ITLC-SG – Acetate and ITLC-SG – Citrate systems. Additionally, migration time was analyzed to evaluate whether the alternative method could offer added benefits. The mean Rs for ITLC-SG – Acetate at 4 cm was 2.43 ± 0.28, while for ITLC-SG – Citrate with added [⁶⁸Ga]GaCl₃ was 5.58 ± 0.23, both exceeding the threshold of 1.5. The mean RCP at 4 cm was 98.90% ± 0.25%, and 99.21% ± 0.19% at 9 cm, with [⁶⁸Ga]Ga-uncomplexed remaining within acceptable limits. No [⁶⁸Ga]GaCl₃ was detected. The coefficient of variation (CV) for RCP between methods was < 2% (0.22%). Operator-based analysis yielded a mean Rs of 3.95 ± 0.06 (CV = 1.52%) and a mean [⁶⁸Ga]Ga-EDOTREOTIDE percentage of 99.60% ± 0.03% (CV = 0.03%). Migration times were significantly reduced with the alternative method (85% reduction). Shortening the migration distance in r-TLC did not compromise specificity, accuracy or robustness while significantly reducing analysis time. The proposed method enhances PET radiopharmaceutical workflows, allowing faster patient dose preparation without quality loss. This approach could be investigated to other [68Ga]Ga-labeled compounds, supporting improved clinical and research applications in nuclear medicine.

For hepatobiliary scintigraphy, the radiopharmaceutical drug, ETIFENIN (TECHIDA®), labelled with technetium-99m, is used as a substitute for MEBROFENIN (CHOLEDIAM®). It is generally accepted that radiopharmaceuticals should be checked prior to injection, in particular by determining radiochemical purity, to ensure high-quality images. Radiochromatographic techniques or methods described in the Summary of Product Characteristics (SmPC) and the European Pharmacopeia (Ph. Eur.) for quality control of [^99mTc]Tc-ETIFENIN were considered impractical in routine nuclear medicine services (e.g. time-consuming and difficult to use). Following a literature review and screening phase, a quality control method was selected using a two-strip method. For detection and quantification of [^99mTc]TcO₄^-, a glass microfiber paper impregnated with silica acid (ITLC-SA®) was used with a NaCl 20% mobile phase (w/v). For [^99mTc]TcO₂, glass microfiber paper impregnated with silica gel (ITLC-SG®) was used together with an absolute methanol mobile phase. The aim of this work was to validate this alternative analytical method. To do so, the recommendations of the European Association of Nuclear Medicine (EANM), adapted from the International Council of Harmonization Q2 (ICH Q2), were followed. Seven parameters were analyzed: specificity, linearity, precision, accuracy, robustness, limit of quantification and range. Additionally, migration time was also evaluated. This two-strip method appears to be specific (Rs_mean > 2.0), linear (slope close to 1, R² ≥ 0.99), precise (CV < 2.0%), accurate (%impurities_{two-strip method} > %impurities_reference), robust (CV < 2.0%), with an acceptable LoQ (S/N > 10:1) and a wide range (1.6-540 MBq/mL). Time of analysis appears to be clearly integrable into routine clinical practices (< 20 min). The alternative two-strip method NaCl 20% - ITLC-SA® and Methanol - ITLC-SG® represents an efficient quality control procedure. It allows the identification and quantification of the ratios of labelled [^99mTc]Tc-ETIFENIN together with two potential impurities consisting of [^99mTc]TcO₄^- and [^99mTc]TcO₂.