Multimodality PET/MRI agents targeted to activated macrophages

The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles have become a popular platform for the fabrication of PET/MRI probes owing to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this article, we report the synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with the positron emitter ⁶⁴Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-⁶⁴Cu-DOTA) bears repetitive anionic charges on the surface that facilitate recognition by scavenger receptor type A (SR-A), a ligand receptor found on activated macrophages but not on normal vessel walls. MDIO-⁶⁴Cu-DOTA has an average iron oxide core size of 7–8 nm, an average hydrodynamic diameter of 62.7 nm, an r ₁ relaxivity of 16.8 mM^?1 s^?1, and an r ₂ relaxivity of 83.9 mM^?1 s^?1 (37 °C, 1.4 T). Cell studies confirmed that the probe was nontoxic and was specifically taken up by macrophages via SR-A. In comparison with the nonmodified analog, the accumulation of MDIO in macrophages was substantially improved. These characteristics demonstrate the promise of MDIO-⁶⁴Cu-DOTA for identification of vulnerable atherosclerotic plaques via the targeting of macrophages.     

Microtubule polymerization: one step at a time

The dynamic assembly of microtubules is a key factor in many of their functions in the cell and recent experiments give new insight into this process at the molecular level.     

Developmental biology: cell intercalation one step beyond

Formation of the primitive streak, the equivalent of the blastopore, is a critical step during the early development of amniote embryos. Medio-lateral cell intercalation and the planar cell polarity pathway play a role during this earliest step of gastrulation in the chick embryo.     

PET: A biological imaging technique

Like in vivo autoradiography, PET provides a means to image and measure rates of biological processes throughout the distributed and interrelated systems of the entire living brain. In addition, both techniques can track and image the functional interactions of the brain with other systems throughout the entire body. Technological advances are yielding higher image spatial resolution and Electronic generators for automated synthesis of positron labeled compounds. The expanding number of labeled compounds (>500) is providing a growing number of biological assays (i.e., substrate metabolism, pre and post synaptic processes, enzyme activity, interaction of medical and illicit drugs with biological systems of the brain, immune system, membrane processes). Studies of normal cerebral function focus on mapping evoked responses of various components of motor, visual, somatosensory, memory and cognitive functions. Cerebral development, neuronal plasticity, and compensatory reorganization to lesions or surgery are active areas of investigation. Various types of assays have been used to identify specific biological alterations, map progression and determine therapeutic responses in a wide variety of neuropsychiatric disorders and drug abuse.Special issue dedicated to Dr. Louis Sokoloff.     

68Ga-PSMA-HBED-CC PET/MRI is superior to multiparametric magnetic resonance imaging in men with biochemical recurrent prostate cancer: A prospective single-institutional study

BackgroundThe primary objective was to compare the overall diagnostic performance, presented as detection rate of ⁶⁸Ga-PSMA-HBED-CC positron emission tomography/magnetic resonance imaging (PSMA PET/MRI) versus conventional, multiparametric MRI (mpMRI) in a population of patients with biochemically recurrent prostate cancer. In conjunction with this analysis, secondary objectives included the evaluation of the detection rate stratified by PSA levels and primary treatment modality.MethodsA total of 165 PSMA PET MRI were performed from April 2018 to May 2021, of whom 108 were presenting for biochemical recurrent disease. The PSMA PET vertex to thigh were read by two different board-certified nuclear medicine physicians while the MRI head and neck, chest, abdomen, and pelvis (with dedicated, PI-RADS compliant multiparametric prostate MRI) were read by two board certified diagnostic radiologists.AnalysisPSMA PET/MRI had a higher detection rate than mpMRI when evaluating patients with biochemical recurrence (BCR) with similar results demonstrated when sub-analysis was performed using PSA levels, primary treatment modality, and time since androgen deprivation therapy. Our study also showed PSMA PET/MRI had a higher sensitivity than mpMRI.DiscussionOur findings demonstrate that PSMA PET/MRI is a better imaging modality in the detection of disease in the setting of BCR when compared to MRI alone. Combined utility with PSMA PET/MRI is a powerful tool which can aid in not only the detection of disease, but also guide in treatment planning for prostate cancer patients.     

Lateral root initiation: one step at a time

Plant growth relies heavily on a root system that is hidden belowground, which develops post-embryonically through the formation of lateral roots. The de novo formation of lateral root organs requires tightly coordinated asymmetric cell division of a limited number of pericycle cells located at the xylem pole. This typically involves the formation of founder cells, followed by a number of cellular changes until the cells divide and give rise to two unequally sized daughter cells. Over the past few years, our knowledge of the regulatory mechanisms behind lateral root initiation has increased dramatically. Here, I will summarize these recent advances, focusing on the prominent role of auxin and cell cycle activity, and elaborating on the three key steps of pericycle cell priming, founder cell establishment and asymmetric cell division. Taken together, recent findings suggest a tentative model in which successive auxin response modules are crucial for lateral root initiation, and additional factors provide more layers of control.     

MRI/PET nonrigid breast-image registration using skin fiducial markers

We propose a finite-element method (FEM) deformable breast model that does not require elastic breast data for nonrigid PET/MRI breast image registration. The model is applicable only if the stress conditions in the imaged breast are virtually the same in PET and MRI. Under these conditions, the observed intermodality displacements are solely due the imaging/reconstruction process. Similar stress conditions are assured by use of an MRI breast-antenna replica for breast support during PET, and use of the same positioning. The tetrahedral volume and triangular surface elements are used to construct the FEM mesh from the MRI image. Our model requires a number of fiducial skin markers (FSM) visible in PET and MRI. The displacement vectors of FSMs are measured followed by the dense displacement field estimation by first distributing the displacement, vectors linearly over the breast surface and then distributing them throughout the volume. Finally, the floating MRI image is warped to a fixed PET image, by using an appropriate shape function in the interpolation from mesh nodes to voxels. We tested our model on an elastic breast phantom with simulated internal lesions and on a small number of patients imaged, with FMS using PET and MRI. Using simulated lesions (in phantom) and real lesions (in patients) visible in both PET and MRI, we established that the target registration error (TRE) is below two pet voxels.     

Complementary emerging techniques: high-resolution PET and MRI

Noninvasive imaging technologies provide a unique window on the anatomy, physiology and function of living organisms. Imaging systems and methods have been developed for the study of small animal model systems that offer exciting new possibilities in neuroscience. Advances in magnetic resonance microscopy and positron emission tomography, and their applications in brain imaging, have provided many benefits to neurobiology, ranging from detailed in vivo neuroanatomy to the measurement of specific molecular targets.     

A step further in the analysis of human bile proteome

Bile was shown to collect proteins known as potential cancer biomarkers. Thorough proteomic analysis of bile is of particular interest to search for new, more sensitive and more specific, biomarkers of cancers affecting the biliary tract and surrounding organs, such as the pancreas and the liver. Therefore, extending the knowledge of the bile proteome is highly relevant, but this has proved technically difficult. In this study, we describe a strategy that circumvents problems related to the biochemical complexity of this sample and the presence of high concentrations of interfering substances. Bile collected from a patient suffering from a biliary stenosis caused by a pancreatic adenocarcinoma was fractionated by a differential centrifugation scheme, involving a stepwise increase in centrifugation speeds. Pellets and the final supernatant were further fractionated by polyacrylamide gel electrophoresis and proteins were in-gel digested prior to LC-MS/MS analysis. This approach allowed the identification of 445 unique proteins with at least two peptides (812 proteins if single-hit proteins were included), which represents a 3-fold increase in the knowledge of bile proteome. The subsequent literature comparison revealed that numerous biliary proteins identified in this sample were related to pancreas cancer. Immunoblot analysis of some known tumor markers revealed that they were preferentially associated with the soluble fraction rather than with pellets containing cellular components.     

Diagnostic Performance of Whole-Body PET/MRI for Detecting Malignancies in Cancer Patients: A Meta-Analysis

BackgroundAs an evolving imaging modality, PET/MRI is preliminarily applied in clinical practice. The aim of this study was to assess the diagnostic performance of PET/MRI for tumor staging in patients with various types of cancer.MethodsRelevant articles about PET/MRI for cancer staging were systematically searched in PubMed, EMBASE, EBSCO and the Cochrane Library. Two researchers independently selected studies, extracted data and assessed the methodological quality using the QUADAS tool. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated per patient and per lesion. The summary receiver-operating characteristic (SROC) curves were also constructed, and the area under the curve (AUC) and Q* estimates were obtained.ResultsA total of 38 studies that involved 753 patients and 4234 lesions met the inclusion criteria. On a per-patient level, the pooled sensitivity and specificity with 95% confidence intervals (CIs) were 0.93 (0.90–0.95) and 0.92 (0.89–0.95), respectively. On a per-lesion level, the corresponding estimates were 0.90 (0.88–0.92) and 0.95 (0.94–0.96), respectively. The pooled PLR, NLR and DOR estimates were 6.67 (4.83–9.19), 0.12 (0.07–0.21) and 75.08 (42.10–133.91) per patient and 10.91 (6.79–17.54), 0.13 (0.08–0.19) and 102.53 (59.74–175.97) per lesion, respectively.ConclusionAccording to our results, PET/MRI has excellent diagnostic potential for the overall detection of malignancies in cancer patients. Large, multicenter and prospective studies with standard scanning protocols are required to evaluate the diagnostic value of PET/MRI for individual cancer types.     

Raf phosphorylation: one step forward and two steps back

We understand Raf-1 activation relatively well but know less about how it is inactivated. An exciting study in this issue of Molecular Cell now describes the molecular basis underlying the transient nature of Raf-1 signaling.     

Diagnostic Efficacy of 18F-FDG PET/MRI in Peripheral Nerve Injury Models

The aim of this study was to evaluate the diagnostic efficacy of ¹⁸F-FDG PET/MRI in two different peripheral neuropathic pain models using the injured rat sciatic nerves. Twelve rats, with operation on left sciatic nerves, were evenly divided into three groups: sham surgery (control group), crushing injury and chronic constriction injury (CCI) (experimental groups). The nerve damage was assessed at 3 weeks postoperatively using following methods: paw withdrawal threshold values (RevWT), maximum standardized uptake values on PET/MRI images (SUVR), and counting the number of myelinated axons in proximal and distal sites of nerve injury (MAxR). The results were quantified and statistically analyzed. Compared to the control group, the crushing injury demonstrated significant differences in RevWT (p < 0.0001) and SUVR (p = 0.027) and the CCI group demonstrated significant differences in RevWT (p < 0.0001), SUVR (p = 0.001) and MAxR (p = 0.048). There were no significant differences between the two experimental groups for all assessments. Correlation analysis demonstrated that RevWT and SUVR assessments were highly correlated (r = -− 0.710, p = 0.010), and SUVR and MAxR were highly correlated (r = 0.611, p = 0.035). However, there was no significant correlation between RevWT and MAxR. The PET scan may be a valuable imaging modality to enable noninvasive, objective diagnosis of neuropathic pain caused by peripheral nerve injury. Also, MRI fused with PET may help clarify the anatomic location of soft tissue structures, including the peripheral nerves.