A single-institution clinical study has identified the concentration of ethanol in 68Ga-labeled PET imaging agents as an independent predictor of moderate-to-severe injection pain, reporting that keeping the stabilizer below 7.85% substantially reduces discomfort for patients undergoing nuclear medicine examinations. The findings, published in EJNMMI Radiopharmacy and Chemistry, offer a quantitative benchmark that radiopharmacies can apply directly when preparing and injecting these short-lived radiotracers.
Intravenous injection of 68Ga-labeled PET radiopharmaceuticals frequently causes pain at the injection site, a problem that goes beyond simple patient comfort because it may also induce vascular spasm and complicate the delivery of the imaging agent. Ethanol is widely used as a stabilizer in 68Ga tracers, helping to preserve the chemical integrity of these compounds, which are produced on-site shortly before use because of the short half-life of gallium-68. However, quantitative evidence linking ethanol concentration specifically to injection pain, and establishing whether that concentration could serve as a predictive marker, had remained insufficient.
The research team enrolled a total of 181 patients for the investigation. The study had two stated aims: to explore the independent factors that influence injection pain and to verify whether ethanol concentration can predict moderate-severe injection pain, with the goal of providing evidence for optimizing clinical radiopharmaceutical preparation and injection workflow.
The initial analysis of pain scores revealed several correlations. Pain scores were positively correlated with female gender, injection volume and ethanol concentration, meaning that higher values in each of these variables were associated with higher reported pain. Conversely, pain scores were negatively correlated with age, so older patients tended to report lower pain scores in this cohort. These correlations pointed toward ethanol concentration as a candidate factor deserving more rigorous statistical testing.
That testing came through multivariate logistic regression, a statistical method that evaluates each potential factor while accounting for the influence of the others. This analysis confirmed ethanol concentration as an independent risk factor for moderate/severe injection pain, with an odds ratio of 6.63 and a 95% confidence interval of 3.80 to 11.56, at a P value below 0.001. In practical terms, patients exposed to higher ethanol concentrations had markedly greater odds of experiencing moderate or severe pain at the injection site, and this association held even after other measured variables were taken into account.
The team then examined how well ethanol concentration performed as a predictor of moderate-severe pain using receiver operating characteristic analysis, a standard approach for evaluating diagnostic or predictive thresholds. The analysis yielded an area under the curve of 0.892, a value indicating strong discriminatory ability. The optimal cutoff value was calculated at 7.85% ethanol concentration, at which point the measure achieved a sensitivity of 82.8% and a specificity of 85.4%. In other words, at this threshold, the ethanol concentration correctly identified the large majority of patients who would go on to experience moderate-severe pain while also correctly classifying most of those who would not.
Stratified analysis provided further support for the clinical relevance of this threshold. When patients were separated according to whether their imaging agent contained ethanol at or below 7.85% or above it, the results showed that controlling ethanol concentration below 7.85% significantly lowered both pain severity and the incidence of moderate-severe pain. This stratified comparison suggests that the threshold is not merely a statistical artifact but corresponds to a meaningful difference in patient experience.
Based on these results, the authors concluded that ethanol concentration in 68Ga-labeled PET imaging agents is an independent predictive factor for moderate-to-severe injection pain, and that limiting ethanol concentration under 7.85% can effectively relieve injection pain and improve patient experience during nuclear medicine examinations. They noted that this quantitative threshold can be directly adopted in routine radiopharmaceutical preparation to reduce injection-related vascular irritation and discomfort for patients.
The study addresses a practical challenge in the growing clinical use of 68Ga-labeled radiopharmaceuticals, which are increasingly employed in PET imaging workflows. Because these agents are compounded shortly before administration, formulation parameters such as stabilizer content are set during preparation, making the reported threshold a directly actionable variable for radiopharmacy teams. The published work appears in EJNMMI Radiopharmacy and Chemistry and was released as an open access research article on 30 October 2026.
Subject of Research: Ethanol concentration as a predictive factor for injection pain in 68Ga-labeled PET radiopharmaceutical administration
Article Title: Investigation on pain factors and ethanol concentration predictive value in 68Ga-labeled PET imaging agent injection
Article References: Yu, M., Zhang, X., Xia, Z., Yi, Y., Shen, X., & Jiang, Y. (2026). Investigation on pain factors and ethanol concentration predictive value in 68Ga-labeled PET imaging agent injection. EJNMMI Radiopharmacy and Chemistry. https://doi.org/10.1186/s41181-026-00483-7
Image Credits: AI Generated
DOI: 10.1186/s41181-026-00483-7
Keywords: 68Ga radiopharmaceuticals, PET imaging, injection pain, ethanol concentration, nuclear medicine, radiopharmacy, logistic regression, ROC analysis, vascular irritation, patient comfort, predictive threshold, Investigation
News Source: Bethany Barker. (November 6, 2026). Ethanol Level in 68Ga PET Tracers Predicts Injection Pain, Study Finds. Scienmag.
