3PC-040 Radiochemical purity determination of 177Lu-PSMA-617: development and validation of a high-performance liquid chromatography analytical method
Bibliographic record
Abstract
Background and Importance 177Lu-PSMA-617 is a treatment of progressive, metastatic, castration-resistant prostate cancers expressing PSMA receptors, previously treated with taxane and at least one second-generation hormone therapy. 177Lu-PSMA-617 is a radiopharmaceutical drug with a marketing authorisation and is manufactured industrially (PLUVICTO®, Novartis). However, it can also be prepared in-house, especially for preclinical applications. Thus, quality control procedures are required to determine radiochemical purity (RCP). Aim and Objectives To develop and validate a radio-high-performance liquid chromatography (HPLC) analysis method to measure RCP of 177Lu-PSMA-617. Material and Methods Radio-HPLC analyses were carried out on an apparatus equipped with a C18 column and a radioactivity detector. Three commercial 177Lu-PSMA-617 batches were used as samples. The parameters considered for method validation were specificity, linearity, accuracy, precision, robustness, limits of detection (LOD) and limits of quantification (LOQ). Means, standard deviations and coefficient of variation (CV) for RCP, retention time (tr) and recovery were calculated. Linear regression coefficient R2 was computed for linearity. Results Radiochemical identification of 177Lu-PSMA-617 consisted in 10 analyses of each three commercial batches and showed a consistent tr of 10.07 min (CV% < 0.1). Recovery was excellent, with 12.87 ± 0.06 MBq recovered at column outlet for a 12.2 MBq injected activity. The addition of radio-impurities in known quantities validated the accuracy of the method (differences between measured RCP and theoretical RCP ranging from 101.57% to 105.52%). CV% of RCP and tr values over 12 measures of a single batch were respectively <0.11% and <0.12%, which confirmed the repeatability of the method. Forced degradation conditions in the presence of acid, base, oxidative stress or heating led to the formation in situ of impurities with a tr largely different from the analyte, confirming the specificity of the method. LOQ and LOD were 0.68 and 0.21 MBq/mL, respectively, and the radiodetector response was linear from 2 to 300 MBq/mL (R2 = 0.9977). Robustness was found to be limited as the mean tr values varied by -4.8% when the column was heated to 50 °C instead of 25 °C. Conclusion and Relevance A radio-HPLC method for the quality control of 177Lu-PSMA-617 was validated and can be used for in-house preparations for preclinical purposes of this radioactive drug. References and/or Acknowledgements Conflict of Interest No conflict of interest.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".