CYP3A4 inhibitors do not influence [68Ga]Ga-DOTA-TATE uptake in liver tissue

Study population

This retrospective study, conducted at the Amsterdam University Medical Centers, location AMC, in the Netherlands, received approval from the local Medical Ethics Assessment Committee. The study included a total of 70 patients who underwent a [68Ga]Ga-DOTA-TATE PET/CT scan between July 2016 and May 2023. As the administration of SSAs is known to be associated with a decreased [68Ga]Ga-DOTA-TATE hepatic uptake [5], patients using SSAs at the time of PET/CT imaging were excluded from the study. The patients were divided into two groups based on their use of CYP3A4 inhibitors. The first group consisted of patients who were taking medications such as clarithromycin, ketoconazole, amiodarone, and verapamil, known inhibitors of CYP3A4, at the time of [68Ga]Ga-DOTA-TATE PET/CT imaging [12]. The second group consisted of patients who did not use medication that influences CYP3A4.

Clinical characteristics

For the statistical analyses, we collected the following data from the electronic health records: sex, age, body mass index (BMI), primary tumour location, presence of a primary tumour, grade and stage of tumour, ki-67 values, injected activity dose and amount of peptide of [68Ga]Ga-DOTA-TATE, treatment with [177Lu]Lu-DOTA-TATE, and medication use [13].

The procedures for labelling [68Ga]Ga-DOTA-TATE, conducting the PET/CT procedure, and performing image analysis have been extensively described elsewhere [13]. In summary, the maximum standardized uptake value (SUVmax) of [68Ga]Ga-DOTA-TATE was calculated on standard iterative reconstructions with a spherical volume of interest (VOI) tool in the primary tumour, the liver (i.e. physiological uptake) and the left psoas major muscle (i.e. background). The following parameters were determined:

SUVmax tumour-to-background ratio (SUVmax TBR) = SUVmax primary tumour/SUVmax psoas major muscle

SUVmax liver-to-background ratio (SUVmax LBR) = SUVmax liver/SUVmax psoas major muscle

SUVmax tumour-to-liver ratio (SUVmax TLR) = (SUVmax primary tumour)/(SUVmax liver)

Statistical analysis

Patient, tumour, and medication characteristics were assessed using descriptive statistics. IBM SPSS Statistics (version 28, IBM, USA) was utilized for all statistical analyses. Categorical variables were presented as frequency with percentage, while continuous variables were reported as mean ± standard deviation (SD) or median with interquartile range (IQR). Fisher's exact test was employed for categorical variables, whereas unpaired T-test or Mann–Whitney U test was used for quantitative variables. All statistical tests were two-tailed, and a p value below 5% was considered statistically significant.

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