Next-Generation Cancer Magnetic Resonance Imaging With Tumor-Targeted Alkylphosphocholine Metal Analogs.

OBJECTIVES: In an effort to exploit the elevated need for phospholipids displayed by cancer cells relative to normal cells, we have developed tumor-targeted alkylphosphocholines (APCs) as broad-spectrum cancer imaging and therapy agents. Radioactive APC analogs have exhibited selective uptake and prolonged tumor retention in over 50 cancer types in preclinical models, as well as over 15 cancer types in over a dozen clinical trials. To push the structural limits of this platform, we recently added a chelating moiety capable of binding gadolinium and many other metals for cancer-targeted magnetic resonance imaging (MRI), positron emission tomography imaging, and targeted radionuclide therapy. The aim of this work was to synthesize, characterize, and validate the tumor selectivity of a new broad-spectrum, tumor-targeted, macrocyclic MRI chelate, Gd-NM600, in xenograft and orthotopic tumor models. A secondary aim was to identify and track the in vivo chemical speciation and spatial localization of this new chelate Gd-NM600 in order to assess its Gd deposition properties. MATERIALS AND METHODS: T1 relaxivities of Gd-NM600 were characterized in water and plasma at 1.5 T and 3.0 T. Tumor uptake and subcellular localization studies were performed using transmission electron microscopy. We imaged 8 different preclinical models of human cancer over time and compared the T1-weighted imaging results to that of a commercial macrocyclic Gd chelate, Gd-DOTA. Finally, matrix-assisted laser desorption and ionization-mass spectrometry imaging was used to characterize and map the tissue distribution of the chemical species of Gd-NM600. RESULTS: Gd-NM600 exhibits high T1 relaxivity (approximately 16.4 s-1/mM at 1.5 T), excellent tumor uptake (3.95 %ID/g at 48 hours), prolonged tumor retention (7 days), and MRI conspicuity. Moreover, minimal tumor uptake saturability of Gd-NM600 was observed. Broad-spectrum tumor-specific uptake was demonstrated in 8 different human cancer models. Cancer cell uptake of Gd-NM600 via endosomal internalization and processing was revealed with transmission electron microscopy. Importantly, tissue mass spectrometry imaging successfully interrogated the spatial localization and chemical speciation of Gd compounds and also identified breakdown products of Gd species. CONCLUSIONS: We have introduced a new macrocyclic cancer-targeted Gd chelate that achieves broad-spectrum tumor uptake and prolonged retention. Furthermore, we have demonstrated in vivo stability of Gd-NM600 by ultrahigh resolution MS tissue imaging. A tumor-targeted contrast agent coupled with the enhanced imaging resolution of MRI relative to positron emission tomography may transform oncologic imaging.

Development and pilot evaluation of a mobile app on parent-child exercises to improve physical activity and psychosocial outcomes of Hong Kong Chinese children.

BACKGROUND: Parent-child exercises involve children and parents to do workout together and have positive effects on physical and mental health. We developed a mobile app on parent-child exercises called Family Move, which combines coaching videos with game features such as points and level system to enhance the health and wellbeing of both children and parents through parent-child exercises. This pilot pre-post study investigated whether the Family Move app-based intervention had a positive effect on children's health-related quality of life (HRQOL), psychosocial wellbeing, and physical activity (PA) level. METHODS: We recruited 67 parent-child pairs. During the 8-week intervention, these pairs were invited to perform parent-child exercises using the Family Move app. Points were automatically added to the user account after viewing a coaching video. In-game ranking was available to enhance user engagement. Parent proxy-report questionnaires on children's HRQOL, psychosocial wellbeing, and PA were administered at baseline and 1- and 6-month follow-up. Paired samples t-tests were conducted to evaluate post-intervention changes in child outcomes (HRQOL, psychosocial wellbeing, and PA). Multiple linear regressions were used to examine these changes as a function of in-game ranking. RESULTS: 52 (78%) viewed at least one coaching video in the Family Move app. Children's PA level significantly increased at 1-month (d = 0.32, p = 0.030) and 6-month (d = 0.30, p = 0.042) follow-up, whereas their psychosocial problems declined at 6-month follow-up (d = 0.35, p = 0.005). Higher in-game ranking was significantly associated with fewer psychosocial problems at 1-month follow-up (ß = - 0.15, p = 0.030). CONCLUSIONS: Our findings suggest that the Family Move app could be a possible intervention to increase children's PA level and psychosocial wellbeing through parent-child exercise. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03279354 , registered September 11, 2017 (Prospectively registered).

Conscious Control Is Associated With Freezing of Mechanical Degrees of Freedom During Motor Learning.

This study investigated whether conscious control is associated with freezing of mechanical degrees of freedom during motor learning. Participants practiced a throwing task using either error-strewn or error-reduced practice protocols, which encourage high or low levels of conscious control, respectively. After 24 hr, participants engaged in a series of delayed retention and transfer tests. Furthermore, propensity for conscious control was assessed using participants' ratings and freezing was gauged through movement variability of the throwing arm. Performance was defined by mean radial error. In the error-strewn group, propensity for conscious control was positively associated with both freezing and performance. In the error-reduced group, propensity for conscious control was negatively associated with performance, but not with freezing. These results suggest that conscious control is associated with freezing of mechanical degrees of freedom during motor learning.

Movement pattern components and mastery of an object control skill with error-reduced learning.

OBJECTIVES: This paper reports the effects of error-reduced learning on movement components and mastery of overhand throwing in children with and without intellectual disability. METHODS: Secondary data analysis was performed on two samples of children (typically developing, TD; intellectual disability, ID) who practiced overhand throwing in either an error-reduced (ER) or error-strewn (ES) condition. Movement pattern components were assessed using a sub-skill of Test of Gross Motor Development-2. RESULTS: In TD participants, ER learners displayed improved follow-through while ES learners did not. Among children with ID, ER learners displayed greater improvements of hip/shoulder rotation and follow-through, than ES learners. Discriminant function analysis confirmed that changes in these components differentiated learning groups. Greater percentage of ER, compared to ES, participants progressed to mastery. CONCLUSIONS: With suppressed errors, the follow-through component of overhand throwing is likely to emerge, particularly in children with inferior abilities, and cognitive limitations. Error-reduced learning facilitates mastery.