The endocannabinoid system modulates neuronal excitability, protects neurons against hyperexcitability and is involved in epileptogenesis in animal models of mesial temporal lobe epilepsy with hippocampal sclerosis. We performed in vivo positron emission tomography imaging of the type 1 cannabinoid receptor in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Twelve patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis received a [¹⁸F]MK-9470 scan to assess type 1 cannabinoid receptor availability in vivo. Parametric modified standard uptake values were used as quantitative measure of type 1 cannabinoid receptor availability and images were spatially normalized to standard space. Voxel-based analysis was performed comparing patients with hippocampal sclerosis to controls and correlations between type 1 cannabinoid receptor status and seizure characteristics were done using volumes of interest. Type 1 cannabinoid receptor positron emission tomography was co-registered with subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging of a complex partial seizure (n = 9). An increased type 1 cannabinoid receptor availability in the ipsilateral temporal lobe was observed, which correlated negatively with the latency since last seizure before scanning and positively to the number of seizures in the month before scanning. A decreased type 1 cannabinoid receptor availability was present in the superior insular cortex, ipsilateral more than contralateral. The ipsilateral insular region displayed a mild ictal hyperperfusion in the transition zone of subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging temporal lobe hyperperfusion-frontal lobe hypoperfusion during complex partial seizures. Type 1 cannabinoid receptor availability showed opposite changes in different brain regions that are involved during complex partial seizures in refractory mesial temporal lobe epilepsy with hippocampal sclerosis. The increase in type 1 cannabinoid receptor availability at the seizure onset zone might be a protective mechanism of neurons against hyperexcitability and seizure activity, or contribute to the process of epileptogenesis, or both. The decreased type 1 cannabinoid receptor availability in the insula may play a role in surround inhibition and prevention of seizure propagation.

Rationale: ^99mTc-trofolastat (^99mTc-MIP-1404), a small-molecule inhibitor of prostate-specific membrane antigen (PSMA), shows high potential to detect prostate cancer (PCa) non-invasively using single-photon-emission-computed-tomography (SPECT). We therefore wanted to assess the performance of ^99mTc-trofolastat SPECT/CT in a phase 2 multi-center, multi-reader prospective study in patients with intermediate- and high-grade PCa, prior to radical prostatectomy and extended pelvic lymph node dissection, with histopathology as gold standard. Methods: 105 PCa patients with an increased risk of lymph node involvement (LNI) received a pelvic ^99mTc-trofolastat SPECT/CT prior to radical prostatectomy with extended pelvic lymph node dissection. Sensitivity of ^99mTc-trofolastat for detection of PCa on a patient- and lobe-basis, using visual and semi-quantitative (tumor-to-background ratio, TBR) scores and of LNI was evaluated as well as correlation of uptake within the gland to Gleason scores (GS) and assessment of the predictive potential of ^99mTc-trofolastat-uptake for LNI. Results: PCa was detected in 98 patients (94%) with acceptable variability between readers. There was a significantly higher visual score and TBR in positive lobes compared to tumor-negative lobes. ROC analysis showed that visual scores more accurately discriminated lobes with GS ≤3+3 from ≥3+4, while TBRs discriminated high-grade disease from normal lobes better. Visual scores and TBRs correlated significantly with GS. ^99mTc-trofolastat SPECT/CT detected LNI with sensitivity of 50%, and specificity of 87% and TBR values significantly predicted LNI with a sensitivity of 90%. Conclusion: ^99mTc-trofolastat SPECT/CT detects PCa with high sensitivity in patients with intermediate- and high-risk PCa compared to histology. It has potential to be used as surrogate marker for Gleason scores and predict LNI.

Convolutional neural networks (CNNs) for brain tumor segmentation are generally developed using complete sets of magnetic resonance imaging (MRI) sequences for both training and inference. As such, these algorithms are not trained for realistic, clinical scenarios where parts of the MRI sequences which were used for training, are missing during inference. To increase clinical applicability, we proposed a cross-modal distillation approach to leverage the availability of multi-sequence MRI data for training and generate an enriched CNN model which uses only single-sequence MRI data for inference but outperforms a single-sequence CNN model. We assessed the performance of the proposed method for whole tumor and tumor core segmentation with multi-sequence MRI data available for training but only $T_{1}$ -weighted ( $T_{\text{1}w}$ ) sequence data available for inference, using BraTS 2018, and in-house datasets. Results showed that cross-modal distillation significantly improved the Dice score for both whole tumor and tumor core segmentation when only $T_{\text{1}w}$ sequence data were available for inference. For the evaluation using the in-house dataset, cross-modal distillation achieved an average Dice score of 79.04% and 69.39% for whole tumor and tumor core segmentation, respectively, while a single-sequence U-Net model using $T_{\text{1}w}$ sequence data for both training and inference achieved an average Dice score of 73.60% and 62.62%, respectively. These findings confirmed cross-modal distillation as an effective method to increase the potential of single-sequence CNN models such that segmentation performance is less compromised by missing MRI sequences or having only one MRI sequence available for segmentation.

The bedside Schwartz equation has long been and still is the recommended equation to estimate glomerular filtration rate (GFR) in children. However, this equation is probably best suited to estimate GFR in children with chronic kidney disease (reduced GFR) but is not optimal for children with GFR >75 mL/min/1.73 m². Moreover, the Schwartz equation requires the height of the child, information that is usually not available in the clinical laboratory. This makes automatic reporting of estimated glomerular filtration rate (eGFR) along with serum creatinine impossible. As the majority of children (even children referred to nephrology clinics) have GFR >75 mL/min/1.73 m², it might be interesting to evaluate possible alternatives to the bedside Schwartz equation. The pediatric form of the Full Age Spectrum (FAS) equation offers an alternative to Schwartz, allowing automatic reporting of eGFR since height is not necessary. However, when height is involved in the FAS equation, the equation is essentially equal to the Schwartz equation for children, but there are large differences for adolescents. Combining standardized biomarkers increases the prediction performance of eGFR equations for children, reaching P10 ≈ 45% and P30 ≈ 90%. There are currently good and simple alternatives to the bedside Schwartz equation, but the more complex equations combining serum creatinine, serum cystatin C, and height show the highest accuracy and precision.

Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting radiopharmaceutical into the circulation of a patient. The radiopharmaceutical will bind to a specific peptide receptor leading to tumor-specific binding and retention. The only target that is currently used in clinical practice is the somatostatin receptor (SSTR), which is overexpressed on a range of tumor cells, including neuroendocrine tumors and neural-crest derived tumors. Academia played an important role in the development of PRRT, which has led to heterogeneous literature over the last two decades, as no standard radiopharmaceutical or regimen has been available for a long time. This review provides a summary of the treatment efficacy (e.g., response rates and symptom-relief), impact on patient outcome and toxicity profile of PRRT performed with different generations of SSTR-targeting radiopharmaceuticals, including the landmark randomized-controlled trial NETTER-1. In addition, multiple optimization strategies for PRRT are discussed, i.e., the dose–effect concept, dosimetry, combination therapies (i.e., tandem/duo PRRT, chemoPRRT, targeted molecular therapy, somatostatin analogues and radiosensitizers), new radiopharmaceuticals (i.e., SSTR-antagonists, Evans-blue containing vector molecules and alpha-emitters), administration route (intra-arterial versus intravenous) and response prediction via molecular testing or imaging. The evolution and continuous refinement of PRRT resulted in many lessons for the future development of radionuclide therapy aimed at other targets and tumor types.