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Hollow mesoporous silica nanoparticle (HMSN) has recently gained increasing interests due to their tremendous potential as an attractive nano-platform for cancer imaging and therapy. However, possibly due to the lack of efficient in vivo targeting strategy and well-developed surface engineering techniques, engineering of HMSN for in vivo active tumor targeting, quantitative tumor uptake assessment, multimodality imaging, biodistribution and enhanced drug delivery have not been achieved to date. Here, we report the in vivo tumor targeted positron emission tomography (PET)/near-infrared fluorescence (NIRF) dual-modality imaging and enhanced drug delivery of HMSN using a generally applicable surface engineering technique. Systematic in vitro and in vivo studies have been performed to investigate the stability, tumor targeting efficacy and specificity, biodistribution and drug delivery capability of well-functionalized HMSN nano-conjugates. The highest uptake of TRC105 (which binds to CD105 on tumor neovasculature) conjugated HMSN in the 4T1 murine breast cancer model was ∼10%ID/g, 3 times higher than that of the non-targeted group, making surface engineered HMSN a highly attractive drug delivery nano-platform for future cancer theranostics. [ABSTRACT FROM AUTHOR]

The present study describes a novel method for the low energy cyclotron production and radiochemical isolation of no-carrier-added 132/135La3+ from bulk natBa. This separation strategy combines precipitation and single-column extraction chromatography to afford an overall radiochemical yield (92 ± 2%) and apparent molar activity (22 ± 4 Mbq/nmol) suitable for the radiolabeling of DOTA-conjugated vectors. The produced 132/135La3+ has a radiochemical and radionuclidic purity amenable for 132La/135La-based cancer theranostic applications. Longitudinal PET/CT images acquired using the positron-emitting 132La and ex vivo biodistribution data separately corroborated the accumulation of unchelated 132/135La3+ ions in bone and the liver. [ABSTRACT FROM AUTHOR]

Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64Cu2+ and trivalent cation 44Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery. [ABSTRACT FROM AUTHOR]

Manganese has long been employed as a T 1 -shortening agent in magnetic resonance imaging (MRI) applications, but these techniques are limited by the biotoxicity of bulk-manganese. Positron emission tomography (PET) offers superior contrast sensitivity compared with MRI, and recent preclinical PET studies employing 52g Mn (t 1/2 : 5.6 d, β + : 29%) show promise for a variety of applications including cell tracking, neural tract tracing, immunoPET, and functional β-cell mass quantification. The half-life and confounding gamma emissions of 52g Mn are prohibitive to clinical translation, but the short-lived 51 Mn (t 1/2 : 46 min, β + : 97%) represents a viable alternative. This work develops methods to produce 51 Mn on low-energy medical cyclotrons, characterizes the in vivo behavior of 51 MnCl 2 in mice, and performs preliminary human dosimetry predictions. 51 Mn was produced by proton irradiation of electrodeposited isotopically-enriched 54 Fe targets. Radiochemically isolated 51 MnCl 2 was intravenously administered to ICR mice which were scanned by dynamic and static PET, followed by ex vivo gamma counting. Rapid blood clearance was observed with stable uptake in the pancreas, kidneys, liver, heart, and salivary gland. Dosimetry calculations predict that 370 MBq of 51 Mn in an adult human male would yield an effective dose equivalent of approximately 13.5 mSv, roughly equivalent to a clinical [ 18 F]-FDG procedure.