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Intrinsically germanium‐69‐labeled super‐paramagnetic iron oxide nanoparticles are synthesized via a newly developed, fast and highly specific chelator‐free approach. The biodistribution pattern and the feasibility of 69Ge‐SPION@PEG for in vivo dual‐modality positron emission tomography/magnetic resonance (PET/MR) imaging and lymph‐node mapping are investigated, which represents the first example of the successful utilization of a 69Ge‐based agent for PET/MR imaging.

This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory.

There is a growing demand for long-term in vivo stem cell imaging for assessing cell therapy techniques and guiding therapeutic decisions. This work develops the production of 52Mn and establishes proof of concept for the use of divalent metal transporter 1 (DMT1) as a positron emission tomography (PET) and magnetic resonance imaging (MRI) reporter gene for stem cell tracking in the rat brain. 52Mn was produced via proton irradiation of a natural chromium target. In a comparison of two 52Mn separation methods, solvent-solvent extraction was preferred over ion exchange chromatography because of reduced chromium impurities and higher 52Mn recovery. In vitro uptake of Mn-based PET and MRI contrast agents (52Mn2+ and Mn2+, respectively) was enhanced in DMT1 over-expressing human neural progenitor cells (hNPC-DMT1) compared to wild-type control cells (hNPC-WT). After cell transplantation in the rat striatum, increased uptake of Mn-based contrast agents in grafted hNPC-DMT1 was detected in in vivo manganese-enhanced MRI (MEMRI) and ex vivo PET and autoradiography. These initial studies indicate that this approach holds promise for dual-modality PET/MR tracking of transplanted stem cells in the central nervous system and prompt further investigation into the clinical applicability of this technique.

Robot-assisted minimally invasive surgery has gained widespread use over the past decade, but the technique is currently operated in the absence of haptic feedback during tissue manipulation. We have developed a complete tactile feedback system, consisting of a piezoresistive force sensor, control system, and pneumatic balloon tactile display, and mounted directly onto a da Vinci surgical robotic system. To evaluate the effect of tactile feedback on robotic manipulation, a group of novices (n = 16) and experts ( n = 4) were asked to perform three blocks of peg transfer tasks with the tactile feedback system in place. Force generated at the end-effectors was measured in all three blocks, but tactile feedback was active only during the middle block. All subjects used higher force when the feedback system was inactive. When active, subjects immediately used substantially less force and still maintained appropriate grip during the task. After the system was again turned off, grip force increased significantly to prefeedback levels. These results demonstrate that robotic manipulations without tactile feedback are done with more force than needed to grasp objects. Therefore, the addition of tactile feedback allows the surgeon to grasp with less force, and may improve control of the robotic system and handling of tissues and other objects.

Old technique, new application: A simple and efficient chelator‐free strategy for the synthesis of a novel dual‐modality PET/MRI agent has been developed. Labeling of radioarsenic (*AsIII and *AsV, *=71, 72, 74, 76) at the surface of superparamagnetic iron oxide nanoparticles (SPIONs) resulted in *As‐SPIONs that can be used for simultaneous PET/MRI in cancer diagnosis, lymph‐node mapping, and potentially for internal radiotherapy.

Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positron-emission tomography (PET) imaging of orthotopic GBM models. 64Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high-contrast PET images of small tumor nodules (∼2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (χ2 = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. We have recently shown that human mesenchymal stem cells (hMSCs) modified to release glial cell line-derived neurotrophic factor (GDNF) decrease disease progression in a rat model of ALS when delivered to skeletal muscle. In the current study, we determined whether or not this effect could be enhanced by delivering GDNF in concert with other trophic factors. hMSC engineered to secrete GDNF (hMSC-GDNF), vascular endothelial growth factor (hMSC-VEGF), insulin-like growth factor-I (hMSC-IGF-I), or brain-derived neurotrophic factor (hMSC-BDNF), were prepared and transplanted bilaterally into three muscle groups. hMSC-GDNF and hMSC-VEGF prolonged survival and slowed the loss of motor function, but hMSC-IGF-I and hMSC-BDNF did not have any effect. We then tested the efficacy of a combined ex vivo delivery of GDNF and VEGF in extending survival and protecting neuromuscular junctions (NMJs) and motor neurons. Interestingly, the combined delivery of these neurotrophic factors showed a strong synergistic effect. These studies further support ex vivo gene therapy approaches for ALS that target skeletal muscle.