Abstract-Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT

Background: In recent years, molecular imaging adressing the C-X-C motif chemokine receptor 4 (CXCR4) has increasingly been utilized in various clinical settings. Here, we aimed to assess radiopharmaceutical uptake and image contrast to determine the most relevant clinical applications for CXCR4-directed imaging. We also investigated the impact of specific activity on scan contrast. Methods: 690 patients with a variety of neoplasms underwent a total of 777 PET/CT scans with 68 Ga-PentixaFor, serving as CXCR4-specific radioligand. A semiquantitative target lesion (TL) analysis was conducted [providing maximum standardized uptake values (SUVmax) and target-to-blood pool ratio (TBR), defined as SUVmax (from TL) divided by mean SUV (from blood pool)]. The applied specific activity (in MBq/µg) was compared to semi-quantitative assessments.Results: Of the 777 scans, 242 did not show discernible uptake in disease sites, leaving 535 PET scans (68.9%) for further analysis. Very high tracer uptake (SUVmax > 12) was found in multiple myeloma (MM; n=113), followed by adrenocortical carcinoma (n=30), mantle cell lymphoma (MCL; n=20), adrenocortical adenoma (n=6) and small cell lung cancer (SCLC; n=12). Providing information on image contrast, comparable results for TBR were recorded, with TBR (>8) in MM, MCL and acute lymphoblastoid leukemia (n=6). When comparing specific activity with semiquantitative parameters, no significant correlation was found for SUVmax or TBR (P ≥ 0.612).Conclusions: In this large cohort, 68 Ga-PentixaFor demonstrated high image contrast in a variety of neoplasms, particularly for hematologic malignancies, SCLC and adrenocortical neoplasms.The present analysis may provide a roadmap to detect patients who may benefit from CXCR4targeted therapies.

Objective: Current workup for the pre-operative distinction between frequent adrenocortical adenomas (ACAs) and rare but aggressive adrenocortical carcinomas (ACCs) combines imaging and biochemical testing. We here investigated the potential of plasma steroid hormone profiling by liquid chromatography tandem mass spectrometry (LC-MS/MS) for the diagnosis of malignancy in adrenocortical tumors. Design: Retrospective cohort study of prospectively collected EDTA-plasma samples in a single tertiary reference center. Methods: Steroid hormone profiling by liquid chromatography tandem mass spectrometry (LC-MS/MS) in random plasma samples and logistic regression modeling. Results: Fifteen steroid hormones were quantified in 66 ACAs (29 males; M) and 42 ACC (15 M) plasma samples. Significantly higher abundances in ACC vs ACA were observed for 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, DHEA, DHEAS and estradiol (all P < 0.05). Maximal areas under the curve (AUC) for discrimination between ACA and ACC for single analytes were only 0.76 (estradiol) and 0.77 (progesterone), respectively. Logistic regression modeling enabled the discovery of diagnostic signatures composed of six specific steroids for male and female patients with AUC of 0.95 and 0.94, respectively. Positive predictive values in males and females were 92 and 96%, negative predictive values 90 and 86%, respectively. Conclusion: This study in a large adrenal tumor patient cohort demonstrates the value of plasma steroid hormone profiling for diagnosis of ACC. Application of LC-MS/MS analysis and of our model may facilitate diagnosis of malignancy in non-expert centers. We propose to continuously evaluate and improve diagnostic accuracy of LC-MS/MS profiling by applying machine-learning algorithms to prospectively obtained steroid hormone profiles.