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Abstract Background The utility for liquid biopsy of tumor‐associated circulating single‐nucleotide variants, as opposed to mutations, of the mitochondrial (mt) and nuclear genomes in neuroblastoma (NB) is unknown. Procedure Variants of the mt and nuclear genomes from tumor, blood cells, and consecutive plasma samples of five patients with metastatic NB that relapsed or progressed were analyzed. Targeted parallel sequencing results of the mt genome, and of the coding region of 139 nuclear genes and 22 miRNAs implicated in NB, were correlated with clinical imaging and laboratory data. Results All tumors harbored multiple somatic mt and nuclear single nucleotide variants with low allelic frequency, most of them not detected in the circulation. In one patient a tumor‐associated mt somatic variant was detected in the plasma before and during progressive disease. In a second patient a circulating nuclear tumor‐associated DNA variant heralded clinical relapse. In all patients somatic mt and nuclear variants not evident in the tumor biopsy at time of diagnosis were found circulating at varying timepoints. This suggests either tumor heterogeneity, evolution of tumor variants or a confounding contribution of normal tissues to somatic variants in patient plasma. The number and allelic frequency of the circulating variants did not reflect the clinical course of the tumors. Mutational signatures of mt and nuclear somatic variants differed. They varied between patients and were detected in the circulation without mirroring the patients' course. Conclusions In this limited cohort of NB patients clinically informative tumor‐associated mt and nuclear circulating variants were detected by targeted parallel sequencing in a minority of patients.

Abstract Background Given the increasing clinical use of PET/MRI, potential risks to patients from simultaneous exposure to ionising radiation and (electro)magnetic fields should be thoroughly investigated as a precaution. With this aim, the genotoxic potential of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and a strong static magnetic field (SMF) were evaluated both in isolation and in combination using the γH2AX assay detecting double-strand breaks in lymphocyte DNA. Methods Thirty-two healthy young volunteers allocated to three study arms were exposed to [18F]FDG alone, to a 3-T SMF alone or to both combined over 60 min at a PET/CT or a PET/MRI system. Blood samples taken after in vivo exposure were incubated up to 60 min to extend the irradiation of blood by residual [18F]FDG within the samples and the time to monitor the γH2AX response. Absorbed doses to lymphocytes delivered in vivo and in vitro were estimated individually for each volunteer exposed to [18F]FDG. γH2AX foci were scored automatically by immunofluorescence microscopy. Results Absorbed doses to lymphocytes exposed over 60 to 120 min to [18F]FDG varied between 1.5 and 3.3 mGy. In this time interval, the radiotracer caused a significant median relative increase of 28% in the rate of lymphocytes with at least one γH2AX focus relative to the background rate (p = 0.01), but not the SMF alone (p = 0.47). Simultaneous application of both agents did not result in a significant synergistic or antagonistic outcome (p = 0.91). Conclusion There is no evidence of a synergism between [18F]FDG and the SMF that may be of relevance for risk assessment of PET/MRI.

Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification.We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid β (Aβ) species concentrations.243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of Aβ38, Aβ40 and Aβ42 were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF Aβ concentrations were calculated.Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than Aβ concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. Aβ38 and Aβ40 correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with Aβ42, the Aβ42/Aβ40 or Aβ42/Aβ38 ratios were found compared to normalization based on cerebellar gray matter.

Abstract  The integrin αvβ3 plays an important role in angiogenesis and tumor metastasis. It is expressed on activated endothelial cells as well as some tumor cells. Therefore it is a promising imaging target as a potential surrogate parameter of angiogenic activity. Molecular imaging of αvβ3 expression could potentially facilitate response evaluation of antiangiogenic drugs (e. g. bevacizumab) or aid in selecting and monitoring patients receiving humanized monoclonal antibody therapies directed against αvβ3 (EMD121974). Therefore many different approaches for imaging of αvβ3 expression have been studied in the recent years, including positron emission tomography (PET), single photon emission tomography (SPECT), magnetic resonance imaging (MRI), optical imaging and ultrasound using targeted microbubbles. While optical imaging techniques lend themselves for preclinical studies, PET and SPECT using the αvβ3 specific tracers [18F]galacto-RGD and [99mTc]NC100692 are the only techniques up to now which have been successfully used in patients. The various advantages and disadvantages of several imaging techniques will be discussed in this article. [ABSTRACT FROM AUTHOR]