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PD-L1 immunohistochemistry correlates only moderately with patient survival and response to PD-(L)1 treatment. Heterogeneity of tumor PD-L1 expression might limit the predictive value of small biopsies. Here we show that tumor PD-L1 and PD-1 expression can be quantified non-invasively using PET-CT in patients with non-small-cell lung cancer. Whole body PD-(L)1 PET-CT reveals significant tumor tracer uptake heterogeneity both between patients, as well as within patients between different tumor lesions.

A major pathological hallmark of Alzheimer's disease is accumulation of amyloid-β in senile plaques in the brain. Evidence is accumulating that decreased clearance of amyloid-β from the brain may lead to these elevated amyloid-β levels. One of the clearance pathways of amyloid-β is transport across the blood-brain barrier via efflux transporters. P-glycoprotein, an efflux pump highly expressed at the endothelial cells of the blood-brain barrier, has been shown to transport amyloid-β. P-glycoprotein function can be assessed in vivo using (R)-[(11)C]verapamil and positron emission tomography. The aim of this study was to assess blood-brain barrier P-glycoprotein function in patients with Alzheimer's disease compared with age-matched healthy controls using (R)-[(11)C]verapamil and positron emission tomography. In 13 patients with Alzheimer's disease (age 65 ± 7 years, Mini-Mental State Examination 23 ± 3), global (R)-[(11)C]verapamil binding potential values were increased significantly (P = 0.001) compared with 14 healthy controls (aged 62 ± 4 years, Mini-Mental State Examination 30 ± 1). Global (R)-[(11)C]verapamil binding potential values were 2.18 ± 0.25 for patients with Alzheimer's disease and 1.77 ± 0.41 for healthy controls. In patients with Alzheimer's disease, higher (R)-[(11)C]verapamil binding potential values were found for frontal, parietal, temporal and occipital cortices, and posterior and anterior cingulate. No significant differences between groups were found for medial temporal lobe and cerebellum. These data show altered kinetics of (R)-[(11)C]verapamil in Alzheimer's disease, similar to alterations seen in studies where P-glycoprotein is blocked by a pharmacological agent. As such, these data indicate that P-glycoprotein function is decreased in patients with Alzheimer's disease. This is the first direct evidence that the P-glycoprotein transporter at the blood-brain barrier is compromised in sporadic Alzheimer's disease and suggests that decreased P-glycoprotein function may be involved in the pathogenesis of Alzheimer's disease.

Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in cancer patients. It is assumed that anti-angiogenic drugs, such as bevacizumab, transiently normalize abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy. To investigate this concept, a study was performed in non-small cell lung cancer (NSCLC) patients using positron emission tomography (PET) and radiolabeled docetaxel ([(11)C]docetaxel). In NSCLC, bevacizumab reduced both perfusion and net influx rate of [(11)C]docetaxel within 5 hr. These effects persisted after 4 days. The clinical relevance of these findings is notable, as there was no evidence for a substantial improvement in drug delivery to tumors. These findings highlight the importance of drug scheduling and advocate further studies to optimize scheduling of anti-angiogenic drugs.

The influence of cannabis on mental health receives growing scientific and political attention. An increasing demand for treatment of cannabis dependence has refueled the discussion about the addictive potential of cannabis. A key feature of all addictive drugs is the ability to increase synaptic dopamine levels in the striatum, a mechanism involved in their rewarding and motivating effects. However, it is currently unknown if cannabis can stimulate striatal dopamine neurotransmission in humans. Here we show that D9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, induces dopamine release in the human striatum. Using the dopamine D 2 /D 3 receptor tracer [ 11 C]raclopride and positron emission tomography in seven healthy subjects, we demonstrate that THC inhalation reduces [11 C]raclopride binding in the ventral striatum and the precommissural dorsal putamen but not in other striatal subregions. This is consistent with an increase in dopamine levels in these regions. These results suggest that THC shares a potentially addictive property with other drugs of abuse. Further, it implies that the endogenous cannabinoid system is involved in regulating striatal dopamine release. This allows new directions in research on the effects of THC in neuropsychiatric disorders, such as schizophrenia.

In a memory clinic setting, combined [(11)C]PIB and [(18)F]FDG PET are of additional value on top of the standard diagnostic work-up, especially when prior diagnostic confidence is low.

Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the emergence of 'self-invented' terms. In order to address these concerns, an international Working Group on 'Nomenclature in Radiopharmaceutical Chemistry and related areas' was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field. Upon open consultation, the following consensus guidelines were agreed, which aim to.

Several methods are in use for analyzing 11 C-Pittsburgh compound-B ( 11 C-PiB) data. The objective of this study was to identify the method of choice for measuring longitudinal changes in specific 11 C-PiB binding. Methods: Dynamic 90-min 11 C-PiB baseline and follow-up scans (interval, 30 6 5 mo) were obtained for 7 Alzheimer disease (AD) patients, 11 patients with mild cognitive impairment (MCI), and 11 healthy controls. Parametric images were generated using reference parametric mapping (RPM2), reference Logan values, and standardized uptake value volume ratios (SUVr), the latter for intervals between 60 and 90 (SUVr 60-90 ) and 40 and 60 (SUVr 40-60 ) minutes after injection. In all analyses, cerebellar gray matter was used as a reference region. A global cortical volume of interest was defined using a probability map-based template. Percentage change between baseline and follow-up was derived for all analytic methods. Results: SUVr 60-90 and SUVr 40-60 overestimated binding with 13% and 10%, respectively, compared with RPM2. Reference Logan values were on average 6% lower than RPM2. Both SUVr measures showed high intersubject variability. Over time, R 1 , the delivery of tracer to the cortex relative to that to the cerebellum, decreased in AD patients (P , 0.05) but not in MCI patients and controls. Simulations showed that SUVr, but not RPM2 and reference Logan values, was highly dependent on uptake period and that changes in SUVr over time were sensitive to changes in flow. Conclusion: To reliably assess amyloid binding over time-for example, in drug intervention studies-it is essential to use fully quantitative methods for data acquisition and analysis.