Association between Randall's Plaque and Calcifying Nanoparticles

Randall's plaques, first described by Alexander Randall in the 1930s, are small subepithelial calcifications in the renal papillae (RP) that also extend deeply into the renal medulla. Despite the strong correlation between the presence of these plaques and the formation of renal stones, the precise origin and pathogenesis of Randall s plaque formation remain elusive. The discovery of calcifying nanoparticles (CNP) and their detection in many calcifying processes of human tissues has raised hypotheses about their possible involvement in renal stone formation. We collected RP and blood samples from 17 human patients who had undergone laparoscopic nephrectomy due to neoplasia. Homogenized RP tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis were performed on fixed RP samples. Immunohistochemical staining (IHS) was applied on the tissue samples using CNP-specific monoclonal antibody (mAb). Randall s plaques were visible on gross inspection in 11 out of 17 collected samples. Cultures of all serum samples and 13 tissue homogenates had CNP growth within 4 weeks. SEM revealed spherical apatite formations in 14 samples, with calcium and phosphate peaks detected by EDS analysis. IHS was positive in 9 out of 17 samples. A strong link was found between the presence of Randall s plaques and the detection of CNP, also referred to as nanobacteria. These results suggest new insights into the etiology of Randall's plaque formation, and will help us understand the pathogenesis of stone formation. Further studies on this topic may lead us to new approaches on early diagnosis and novel medical therapies of kidney stone formation

Cerebral FDG Metabolic Pattern in Pediatric Patients with Neurofibromatosis Type 1: A Retrospective Study

Aims: Learning disabilities represent the most significant cause of lifetime morbidity in neurofibromatosis type 1 (NF1) patients. The cognitive phenotype of NF1 pediatric patients is not well understood. The purpose of this study was to examine the cerebral glucose metabolic pattern in NF1 pediatric patients. Study Design: Retrospective. Place and Duration of Study: Saint Louis University Hospital, Saint Louis, Missouri, United States, between May 2011 and May 2012. Methodology: Six NF1 pediatric patients underwent FDG PET/CT including the brain, for evaluation of extracranial neoplasm. Their brain PET images were compared with a pediatric comparison set (21 subjects) using Statistical Parametric Mapping. Significant differences between groups were examined at p<0.001, uncorrected for voxel height and p<0.05, corrected for cluster extent. Results: Compared with the comparison set, the 6 NF1 patients showed the largest cluster of reduced FDG uptake (3966 voxels) in the medial dorsal nucleus of bilateral thalami. Additional clusters of metabolism in the range from 415 to 926 voxels were noticed in the right cingulate gyrus (Brodmann area (BA) 8 and 24), left occipital lobe (BA 17 and 18) and right fronto-parietal lobe (BA 43). Conclusion: The FDG reduction of the bilateral thalami is compelling and may be most pathognomonic for NF1. This and other areas of FDG reduction found within the brain may contribute to a better understanding of the NF1 cognitive phenotype

Assessment of an 18F-Labeled Phosphoramidate Peptidomimetic as a New Prostate-Specific Membrane Antigen–Targeted Imaging Agent for Prostate Cancer

Prostate-specific membrane antigen (PSMA) is a transmembrane protein commonly found on the surface of late-stage and metastatic prostate cancer and a well-known imaging biomarker for staging and monitoring therapy. Although 111 In-labeled caprop-mab pendetide is the only approved agent available for PSMA imaging, its clinical use is limited because of its slow distribution and clearance that leads to challenging image interpretation. A small-molecule approach using radiolabeled urea-based PSMA inhibitors as imaging agents has shown promise for prostate cancer imaging. The motivation of this work is to explore phosphoramidates as a new class of potent PSMA inhibitors to develop more effective prostate cancer imaging agents with improved specificity and clearance properties