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Introduction The human epidermal growth factor receptor 2 (HER2) status is important for HER2 targeting therapies. T his information is obtained through immunohistochemistry (IHC) or in situ hybridisation (ISH), which necessitates tissue sampling, and may miss tumor heterogeneity as not every lesion consists of the same cells, nor expresses the same levels of HER2. To assess multiple lesions, whole-body imaging using PET/CT imaging might be a solution. A 68Ga-labeled, NOTA-coupled, single-domain antibody (sdAb) targeting the HER2 receptor has been developed (1). Methods In this phase II trial, 20 patients (pts) with locally advanced or metastatic breast carcinoma (BC) were included. Pts were injected intravenously with a typical dose of 100 ug and an activity range of 98-168 MBq 68GaNOTA-anti-HER2 sdAb, followed by PET/CT (Siemens Biograph Vision, 120 s per bed position and 40 s for the legs) at 90 min post injection (pi). A 2nd tracer injection, followed by PET/CT with identical parameters, was done within 8 days. In both image data sets, up to 5 lesions (minimal diameter 12mm, for lymph nodes in the short axis) per pt were selected with no more than 2 per organ system. Peak Standard Uptake Values (SUVpeak) of selected lesions were measured on both scans with Siemens' Syngo.via VB40 and compared with student t-test and Bland-Altman Plots for differences. Results/Discussion Out of 20 pts included with BC (6 HER2+, 14 HER2-) with a mean age of 58.6 y (37-81), three were scanned only once: one owing to the COVID-19 pandemic and two due to withdrawal of consent. An example of repeated tracer injection and subsequent imaging is shown in fig. 1. No safety concerns were identified in these 20 patients, confirming the excellent safety of this imaging tracer. For repeatability analysis, 50 lesions were delineated by a study team member on both scans in 17 pts. No significant differences between the two measurements were found (p:0.40). The repeatability coefficient (RC) was 38.2%. The mean absolute percentagedifference (MAPD), which is the mean of 1100x(SUV2- all subjects, was 13.6%, comparable to repeated values reported for 18F-FDG (2). Bland-Altman plot with the relative difference is shown in Fig. 2. Independent uptake analysis of all lesions by a central image reviewer, blinded to the HER2 status of the patient is ongoing. Conclusions This study confirms that on PET/CT imaging in patients with breast carcinoma, SUVpeak is a highly repeatable metric for quantifying 68GaNOTA-anti-HER2 sdAb uptake in subsequent scans. lts repeatability is similar to that reported for other routinely used tracers, such as FDG. Additional studies to define the potential clinical benefit of this technique are currently ongoing.

Background: Human epidermal growth factor receptor 2 (HER2) status is an important predictive biomarker in breast cancer (BC). Tumor heterogeneity has been described, with changes in HER2 expression levels between lesions and over the disease course. HER2 expression is assessed on tissue biopsies, at primary diagnosis and in metastatic lesions. A whole-body imaging technique such as PET/CT could help understand expression levels in different lesions. A 68Ga-labeled single domain antibody (sdAb) targeting the HER2 receptor has been developed and proven safe (Keyaerts et al., 2016). Imaging is performed at 90 min post-injection (pi). We report results of a phase II trial to assess the repeatability of the technique in 20 patients and the correlation of tracer uptake with HER2 tissue expression of the lesions present at the time of imaging. Methods: Twenty patients (pts) with a locally advanced or metastatic BC with at least one lesion of minimum 12 mm were included. Pts were injected intravenously with a typical protein mass of 100 µg and a radioactive dose ranging from 98-168 MBq 68GaNOTA-anti-HER2 sdAb. PET/CT images were obtained at 90 min pi. A second tracer injection followed by PET/CT was done with a maximal interval of 8 days. To assess repeatability, up to 5 lesions per pt were selected, with no more than 2 in a single organ. Peak Standard Uptake Values (SUVpeak) of the lesions were measured on both scans and compared with a t-test and Bland-Altman Plots. Images were compared to other available medical or imaging data and interpreted considering the subject’s disease course. Serum and plasma samples were collected before injection and between 60 and 365 days pi and stored for future detection of anti-drug antibodies (ADA) and liquid biopsies analysis for the presence of HER2 amplification. Tissue samples were assessed by central labs using mass spectrometry, immunohistochemistry and in fluorescence situ hybridization. Results: Twenty women with BC (6 HER2+, 14 HER2-) with a mean age of 58.6 y (37-81) were included. Three pts were scanned only once (2 due to withdrawal of consent, 1 due to covid pandemic). Repeatability of the technique was visually scored as excellent. For quantification, 50 lesions were compared on both scans in 17 pts without significant differences between the two measurements (p=0.40). The repeatability coefficient (RC) was 38.2%. The mean absolute percentage difference (MAPD) was 13.6%, comparable to repeat values reported for 18F-FDG. In 3 out of 6 HER2-positive (HER2+) patients, lesions showed high uptake, even better visible than using 18F-FDG in 2 of them. In 2 HER2+ subjects with a negative scan, lesions were confirmed to be true negatives: one patient did not relapse from BC but had tuberculosis; the other was confirmed to have a radiopneumonitis after radiotherapy and no relapse. In 1 HER2+ patient, the uptake was unexpectedly low. However, the HER2 status was also not reconfirmed in the metastatic setting for this subject. In 1 HER2-negative patient, the tumor HER2 status was changed from negative to positive based on a subsequent image-guided biopsy performed in this study. High tracer uptake was also seen in many of the patients presenting with HER2-low BC (IHC 1+ or 2+), indicating the potential of the tracer to detect low-level HER2 expression. Additional correlation to centrally performed tissue and blood analysis is ongoing. Conclusion: 68GaNOTA-Anti-HER2 PET/CT shows high uptake in HER2-expressing BC lesions but also in HER2-low lesions. The technique shows good repeatability and, in some cases, even better sensitivity than 18F-FDG PET/CT. Specificity was confirmed in relapse-free lesions such as tuberculosis and radiopneumonitis. Its sensitivity makes it a promising technique to assess HER2+ and HER2-low lesions in BC patients.

Background and Goal of Study: The influence of gender on anaesthesia remains poorly understood, nevertheless there is growing evidence suggesting that gender may be an independent factor influencing the PKs. The purpose of this study was to investigate the influence of gender on real blood propofol concentrations during TCI. Materials and Methods: 20 euthyroid patients, aged 18-70 year, ASA I to II, scheduled for elective thyroid surgery were included. Level of hypnosis was monitored with Neurosense monitor and analgesic level was monitored with an ANI index . A radial arterial catheter was inserted in the contralateral arm of infusion, for blood sampling and for continuous monitoring of BP and CO. A TCI of sufentanil was started with a target ef fect (Ce )of 0.3 ng/ml (PK Gepts) followed by the TCI of propofol, targeting a predicted blood concentration (Cp) of 4 μg/ml ( PK- Schnider). The Cp of propofol was increased or decreased if the neurowave index was >60 or 70. Arterial blood samples were collected at at well defined timepoints. At each time point, the PE was calculated as PE(%) = (Cm-Cp)/Cpx100 where Cm and Cp are the measured and predicted blood concentrations. Results and Discussion: 7 men and 13 women were included in this study. No dif ference in age was found between men and women, 56.71 (st.dev. 11.07) and 55.38 (7.59) years respectively (P=0.754). Repeated measures ANOVA showed a significant drop in CO at 15 and 30 min af ter start TCI compared to baseline in women (p = 0.00004 and p =0.004) . On average women showed a significant higher PE (M= 58.93, SE 2.95) than men (M= 28.18, SE 3.88). PE increases slightly with increased sufentanil Ce and these increase was higher in women ( 14.16% vs 3.61% respectively). Light hypothermy had higher influence on PE in man compared to women (increase 11.12% vs 3.42%). An inverse relation between CO and propofol Cp may explain the higher bias observed in women. Conclusion(s): Gender seems to have an impact on propofol PKs in our thyroid population.

Background and Goal of Study: TCI is a widely used technique. However weneed to bear in mind that the PK-models used never or just by chance matchthe PK characteristics of our patient. A Pelorus 1500 propofol measurementsystem has been developed (Sphere Medical, Cambridge, UK), which is designedfor rapid analysis of propofol concentration in whole blood samples.The purpose of this study was to test the usefulness of the Pelorus during TCIof propofol.Materials and Methods: 20 patients, ASA I to II, scheduled for thyroid surgerywere included. Standard monitoring included ECG, pulse oxymetry, NIBP. Thelevel of hypnosis was monitored with a Neurosense monitor and the analgesiclevel with a ANI monitor (Metrodoloris, Lille, France). A radial arterial catheterwas inserted in the contralateral arm of the infusion for blood sampling andwas connected to a FloTrack for continuous monitoring of BP and CO. A TCIof sufentanil was started with a target ef fect (Ce) of 0.3 ng/ml (PK-Gepts) followedby the TCI of propofol , targeting a predicted blood concentration (Cp)of 4 μg/ml ( PK- Schnider). The Cp of propofol was increased or decreased ifthe neurowave index was >60 or 70. Arterial blood samples formeasurements of propofol (Cm) were collected at well-defined time-pointsuntil 2 hours af ter the end of infusion.Results and Discussion: A total of 261 samples were analyzed. Cm rangedfrom 0.09 to 12.04 mg/ml. The performance errors (PE) were distributedaround a range of -70% to 201% when plotted against the predicted concentrationswith a median value of 47.33%. The PE increased slightly (2.35%) withhigher sufentanil.Whole blood analysis and simultaneous sufentanil may perhaps explain the high bias.Conclusion(s): Pelorus1500 can be a useful tool to better understand propofolPKs.

Introduction: AI’s are the preferred adjuvant hormonal treatment for postmenopausal(PM) estrogen receptor positive (ER+) disease because of the improved efficacy over tamoxifen in terms of disease free survival and reduction in distant recurrence. AI’s have been associated with increased bone loss by blocking peripheral tissue estrogen synthesis, arthralgia and a negative effect on lipid metabolism. In this prospective study we wanted to assess the amount of bone loss and the changes in lipid levels in early breast cancer(EBC) patients (pts) treated with 3yrs of extended letrozole as part of the SOLE study after 5 yrs of adjuvant AI. Objectives: the primary objective of the study is to calculate the mean percentage change in bone mineral density(BMD)(g/cm2) after 8 yrs of letrozole and to compare between the continuous(C) and intermittent(I) intake of letrozole. The secondary objectives are to correlate the mean change in BMD with the initial value, BMI and to describe the evolution of the lipid levels in both groups. Patients and methods: BMD was measured at the lumbar spine (L2-4) and hip by dual energy X-ray absorptiometry (DEXA) in PM pts. with ER+ EBC. We also measured the fasting lipid levels baseline and after 8 yrs of an AI. Differences between the two groups were assessed by the independent samples T-test and the correlation by the linear regression analysis. Results: Fifty four pts were included in the study with a mean age of 62.5 yrs(+/-8.6 yrs). Seventeen pts are too early to be evaluable, 8 pts stopped letrozole due to adverse events and 2 pts had no baseline DEXA values. Two pts received tamoxifen 2 to 5 yrs before inclusion in the SOLE study. The remaining 25 pts showed a mean change in BMD for the lumbar spine of -1.1 (10.6SD) and for the hip -4.4 (7.04SD). Currently 13 pts in the C arm demonstrated a mean decrease in BMD for the (LS) of -2.7(10.2SD), and for the hip of -2.7(5.5SD). Twelve pts included in the I arm experienced a mean increase in BMD for the LS of 0.65(SD11.2) and a mean decrease in BMD for the hip of -4.9(9.1SD). The difference between the two treatment groups was not significant for the LS measurements after 8yrs (p=0.4) nor for the hip (p=0.23) neither was it at baseline (p=0.9; 0.1). Only three pts had fractures due to trauma. The overall fracture rate was only 0.05%.There was no correlation with the BMI, but there was a significant correlation with baseline BMD.(p=0.002)The mean fasting cholesterol levels at 8yrs in the C arm was 214mg/dl(41.3SD) and in the I arm was 218mg/dl(35.6SD)and was not significantly different(p=0.8), nor was it at baseline(p=0.5). Conclusion: This first prospective long term BMD and lipid follow-up study in PM EBC pts taking adjuvant letrozole beyond 5 yrs shows a decline in BMD. Until now no significant differences were observed between continuous and intermittent letrozole. An updated and detailed follow-up on more patients will be presented.

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