Validation of HPLC and TLC analytical methods to determine radiochemical purity of 99mTc-cAbVCAM1-5, a new experimental radiotracer.

Cardiovascular diseases, including fatal myocardial infarctions from atheromatous plaques, are the primary global mortality cause. Detecting stenotic atheromatous plaques is possible through coronary angiography, but vulnerable plaques with eccentric remodeling are undetectable with current diagnostic methods. Addressing this challenge, our group developed a radiopharmaceutical drug targeting vascular cell adhesion molecule 1 (VCAM-1), radiolabeled with technetium-99m. Given the absence of a monograph in the European Pharmacopoeia, and in order to draft the investigational medicinal product documentation, analytical methods had to be validated by high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) to determine the radiochemical purity (RCP) of 99mTc-cAbVCAM1-5. This study therefore presents the results of the validation of analytical methods obtained in this context. The method validation followed the European Association of Nuclear Medicine (EANM) recommendations adapted from ICH Q2(R1), ensuring conformity with specificity, accuracy, repeatability and intermediate precision, linearity, robustness, quantification limit (LoQ), and range criteria. Regarding the results of specificity, both HPLC and TLC methods demonstrated excellent separation of 99mTc-cAbVCAM1-5 from impurities 99mTcO4-. Accuracy results indicated recovery percentages within the range of 99.52-101.40% for the HPLC and 99.51-101.97% for TLC, ensuring reliable measurements for each concentration of 99mTcO4-. Precision of the methods was validated by assessing repeatability and intermediate precision. Linearity was determined over the usual concentrations range and the correlation coefficient was greater than 0.99 for both methods. The limit of quantification was measured by diluting the 99mTcO4- to obtain a signal-to-noise ratio of around 10:1. Under these conditions, we obtained an LOQ of 2.10 MBq/mL for HPLC and 2Mbq/mL for TLC. In conclusion, the analytical methods developed in this study comply with EANM recommendations. This therefore allows us to correctly assess the radiochemical purity of 99mTc-cAbVCAM1-5, a new radiotracer targeting inflammation in vulnerable plaques.

Investigating the link between drug consumption and adverse events reporting in France.

The objective of this study is to examine the potential association between drug use and adverse event reporting in France. A number of drug users and cases reported were extracted from the French Health Care Insurance database (Open Medic) and the French pharmacovigilance database. We performed two separate mixed-effect models (with a drug used or reporting rate as dependent variables) with a random intercept for drug classes. We selected 62 drugs from 10 drug classes, for which 177 364 cases were reported in the French pharmacovigilance database in 2020. The results showed a strong association between drug users and the number of reported cases in France among each drug class (P < 0.01). Within a drug class, the number of reported cases is, therefore, a proxy for the exposure to a given drug in the population. This finding could be useful to approximate and compare drug exposure from pharmacovigilance databases.

Sotorasib associated with tacrolimus and everolimus: A significant drug interaction in lung transplant patients.

The management of immunosuppressors in solid organ transplantation requires pharmacological therapeutic monitoring with regular adaptation of the dosage to the residual level. An obvious cause of these fluctuations is drug interactions, particularly for mTOR inhibitors and anti-calcineurin drugs, which are highly metabolized by cytochromes P450. A 72-year-old lung transplanted man, treated by tacrolimus and everolimus in the long term, had his residual immunosuppressor levels unbalanced by the introduction of sotorasib, which is used for metastatic pulmonary adenocarcinoma. This imbalance is explained by the fact that sotorasib is an inducer of CYP3A4 and an inhibitor of PGP, but the strength of the interaction has never been studied. This will have required a threefold increase in dosages and weekly monitoring before satisfactory residual levels were achieved.

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1.

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.