The adhesion molecule P-selectin is present on the cell surface of both activated endothelium and activated platelets. The present study describes the pharmaceutical development, safety evaluation, and preclinical efficacy of a micro-dosed radiotracer. The macromolecular nanoscale assembly consisted of a natural compound made of a sulfated fucose-rich polysaccharides (fucoidan) and a radionuclide (technetium-99m) for the detection of P-selectin expression in cardiovascular diseases. After extraction and fractionation from brown seaweeds, the good manufacturing practice (GMP) production of a low molecular weight (LMW) fucoidan of 7 kDa was achieved and full physicochemical characterization was performed. The regulatory toxicology study in rats of the GMP batch of LMW fucoidan revealed no adverse effects up to 400 μg/kg (×500 higher than the expected human dose) and pseudoallergy was not seen as well. In a myocardial ischemia-reperfusion model in rats, the GMP-grade LMW fucoidan labeled with technetium-99m detected P-selectin upregulation in vivo. The present study supports the potential of using ^99mTc-fucoidan as an imaging agent to detect activated endothelium in humans.

Purpose: In routine practice, dopamine transporter (DAT) imaging is frequently used as a diagnostic tool to support the diagnosis of Parkinson’s disease or dementia with Lewy bodies. In 2008, we published a review on which medications and drugs of abuse may influence striatal [¹²³I]I-FP-CIT binding and consequently may influence the visual read of an [¹²³I]I-FP-CIT SPECT scan. We made recommendations on which drugs should be withdrawn before performing DAT imaging in routine practice. Here, we provide an update of the original work based on published research since 2008. Methods: We performed a systematic review of literature without language restriction from January 2008 until November 2022 to evaluate the possible effects of medications and drugs of abuse, including the use of tobacco and alcohol, on striatal DAT binding in humans. Results: The systematic literature search identified 838 unique publications, of which 44 clinical studies were selected. Using this approach, we found additional evidence to support our original recommendations as well as some new findings on potential effect of other medications on striatal DAT binding. Consequently, we updated the list of medications and drugs of abuse that may influence the visual read of [¹²³I]I-FP-CIT SPECT scans in routine clinical practice. Conclusion: We expect that a timely withdrawal of these medications and drugs of abuse before DAT imaging may reduce the incidence of false-positive reporting. Nevertheless, the decision to withdraw any medication must be made by the specialist in charge of the patient’s care and considering the pros and cons of doing so.

Background: Accurate sentinel lymph node (SLN) staging is essential for both prognosis and treatment in patients with breast cancer. However, the preoperative lymphoscintigraphy may fail to visualize the SLN in some patients. The purpose of this retrospective study was to identify risk factors associated with SLN nonvisualization on lymphoscintigraphy. For this single-center retrospective study, all data of lymphoscintigraphy of SLN procedures from March 2011 to April 2021 were collected and reviewed from the Amsterdam UMC database. Results: A total of 1886 SLN procedures were included in this study. The SLN nonvisualization rate was 25.1% on lymphoscintigraphy at 4 h post-injection. The SLN nonvisualization rate decreased to 9.4% after reinjection. Multivariable analysis showed that age ≥ 70 years (P < 0.001; OR: 2.27; 95% CI: 1.46–3.53), BMI ≥ 30 kg/m² (P = 0.031; OR: 1.48; 95% CI: 1.04–2.12) and nonpalpable tumors (P = 0.004; OR: 1.54; 95% CI: 1.15–2.07) were independent predictors of SLN nonvisualization. Tumor location, brand of radiopharmaceutical, injected dose and volume, experience of preparer and administrator were not associated with SLN nonvisualization. None of the patient, tumor or tracer characteristics were associated with SLN nonvisualization after radiotracer reinjection. Conclusions: This study shows that risk factors for SLN nonvisualization in breast cancer patients during preoperative lymphoscintigraphy are age ≥ 70 years, BMI ≥ 30 kg/m² and nonpalpable tumors. Our results support the notion that SLN lymphoscintigraphy is a very robust technique that does not depend on the experience of the preparer or administrator of the radiotracer.

Ageing changes the impact of nutrition, whereby inflammation has been suggested to play a role in age-related disabilities such as diabetes and cardiovascular disease. The aim of this study was to investigate differences in postprandial bile-acid response and its effect on energy metabolism between young and elderly people. Nine young, healthy men and nine elderly, healthy men underwent a liquid mixed-meal test. Postprandial bile-acid levels, insulin, glucose, GLP-1, C4, FGF19 and lipids were measured. Appetite, body composition, energy expenditure and gut microbiome were also measured. The elderly population showed lower glycine conjugated CDCA and UDCA levels and higher abundances of Ruminiclostridium, Marvinbryantia and Catenibacterium, but lower food intake, decreased fat free mass and increased cholesterol levels. Aging is associated with changes in postprandial bile-acid composition and microbiome, diminished hunger and changes in body composition and lipid levels. Further studies are needed to determine if these changes may contribute to malnutrition and sarcopenia in elderly.

Purpose: A high SUV_max tumor-to-liver ratio (TLR) of ⁶⁸Ga-DOTATATE can be used to select patients with neuroendocrine tumors (NETs) for peptide receptor radionuclide therapy (PRRT). In addition, an SUV_max TLR ≥ 8.1 is associated with increased progression-free survival in NET patients treated with somatostatin analogs (SSAs). To avoid a theoretical interaction, several guidelines recommend performing PET/CT just before the monthly administration of long-acting SSAs. We aimed to investigate the effect of SSA on the SUV_max of ⁶⁸Ga-DOTATATE in patients with NET and to identify independent predictors for high SUV_max TLR. Patients and Methods: For this retrospective study, 192 ⁶⁸Ga-DOTATATE PET/CT scans of 165 patients without (n = 115) and with (n = 77) SSA (octreotide or lanreotide) in the 3 months before PET/CT were collected and reviewed. The effect of SSA on SUV_max values was analyzed by a maximum likelihood mixed model. Results: Patients with SSA had a significantly higher median SUV_max TLR than patients without SSA (4.7 [IQR], 3.1–7.7) versus 3.2 [IQR, 2.0–5.4]; P < 0.001). Multivariable logistic regression analysis showed that SSA use was an independent predictor for SUV_max TLR ≥ 8.1 (odds ratio, 2.91; 95% confidence interval, 1.26–6.72; P = 0.012). Conclusions: Our data suggest that higher SSA concentrations do not have a negative effect on ⁶⁸Ga-DOTATATE uptake in tumor lesions. In addition, we found that only SSA use was associated with SUV_max TLR ≥ 8.1. Our results are consistent with previously conducted studies and in line with the recently published guideline that suggests that the relatively recent use of SSA does not necessitate any delay in ⁶⁸Ga-DOTATATE PET/CT imaging.

Background: Increased vascular permeability is an early sign of vascular damage and can be measured with the transcapillary escape rate of albumin (TER_alb). Although TER_albhas a multi-exponential kinetic model, most published TER_albdata are based on mono-exponential kinetic models with variation in blood sampling schemes. Aim of this posthoc study was to evaluate the influence of variation in blood sampling schemes and the impact of mono- or bi-exponential analyses on the calculation of TER_alb. Study participants were part of a cross-over intervention study protocol, investigating effects of sodium loading on blood pressure, endothelial surface layer and microcirculation. Multiple blood samples were drawn between 3 and 60 min after injection of radioactive iodide labeled human serum albumin (rHSA).Results: In total 27 male participants with 54 measurements were included. For all participants the maximum serum radioactivity was reached within 20 min, while 85% of the participants had their maximum serum activity within 10 min. The TER_albcalculated with the subsequently chosen T_{20–60 min}reference scheme (6.19 ± 0.49%/h) was significantly lower compared to the TER_albof the T_{3–60 min}, T_{5–60 min}, and T_{max – 60 min}schemes. There was no significant difference between the T_{20–60 min}reference scheme and the T_{10–60 min}and T_{15–60 min}schemes. Bi-exponential kinetic modeling did not result in significant different observations compared to the mono-exponential kinetic analysis.Conclusions: As there is variation in the timing of the maximum serum radioactivity of rHSA, blood sampling schemes starting before 10 min after administration of rHSA will result in a significant overestimation of TER_alb. In addition, variation in kinetic modeling did not result in significant changes in TER_alb. Therefore, we emphasize the need to standardize TER_alband for practical and logistical reasons advocate the use of a mono-exponential model with blood sampling starting 20 min after rHSA administration.