XFCT-MRI hybrid multimodal contrast agents for complementary imaging.

Multimodal contrast agents in biomedical imaging enable the collection of more comprehensive diagnostic information. In the present work, we design hybrid ruthenium-decorated superparamagnetic iron oxide nanoparticles (NPs) as the contrast agents for both magnetic resonance imaging (MRI) and X-ray fluorescence computed tomography (XFCT). The NPs are synthesized via a one-pot polyol hot injection route, in diethylene glycol. In vivo preclinical studies demonstrate the possibility of correlative bioimaging with these contrast agents. The complementarity allows accurate localization, provided by the high contrast of the soft tissues in MRI combined with the elemental selectivity of XFCT, leading to NP detection with high specificity and resolution. We envision that this multimodal imaging could find future applications for early tumor diagnosis, improved long-term treatment monitoring, and enhanced radiotherapy planning.

Longitudinal In-Vivo X-Ray Fluorescence Computed Tomography With Molybdenum Nanoparticles.

X-ray fluorescence computed tomography (XFCT) with nanoparticles (NPs) as contrast agents shows potential for molecular biomedical imaging with higher spatial resolution than present methods. To date the technique has been demonstrated on phantoms and mice, however, parameters such as radiation dose, exposure times and sensitivity have not yet allowed for high-spatial-resolution in vivo longitudinal imaging, i.e., imaging of the same animal at different time points. Here we show in vivo XFCT with spatial resolution in the 200- [Formula: see text] range in a proof-of-principle longitudinal study where mice are imaged five times each during an eight-week period following tail-vein injection of NPs. We rely on a 24 keV x-ray pencil-beam-based excitation of in-house-synthesized molybdenum oxide NPs (MoO2) to provide the high signal-to-background x-ray fluorescence detection necessary for XFCT imaging with low radiation dose and short exposure times. We quantify the uptake and clearance of NPs in vivo through imaging, and monitor animal well-being over the course of the study with support from histology and DNA stability analysis to assess the impact of x-ray exposure and NPs on animal welfare. We conclude that the presented imaging arrangement has potential for in vivo longitudinal studies, putting emphasis on designing biocompatible NPs as the future focus for active-targeting preclinical XFCT.

Induction of protective CTL immunity against peptide transporter TAP-deficient tumors through dendritic cell vaccination.

A large proportion of human cancers show deficiencies in the MHC class I antigen-processing machinery. Such defects render tumors resistant to immune eradication by tumoricidal CTLs. We recently identified a unique population of CTL that selectively targets tumor immune-escape variants through recognition of MHC-presented peptides, termed TEIPP (T cell epitopes associated with impaired peptide processing), expressed on cells lacking functional TAP-peptide transporters. Previously, we showed that vaccination with TEIPP peptides mediates protection against TAP-deficient tumors. Here, we further explored the concept of TEIPP-targeted therapy using a dendritic cell (DC)-based cellular vaccine. Impairment of TAP function in DC induced the presentation of endogenous TEIPP antigens by MHC class I molecules, and immunization with these DCs protected mice against the outgrowth of TAP-deficient lymphomas and fibrosarcomas. Immune analysis of vaccinated mice revealed strong TEIPP-specific CTL responses, and a crucial role for CD8(+) cells in tumor resistance. Finally, we show that TEIPP antigens could be successfully induced in wild-type DC by introducing the viral TAP inhibitor UL49.5. Our results imply that immune intervention strategies with TAP-inhibited DC could be developed for the treatment of antigen processing-deficient cancers in humans.

The transcriptional map of the common eliminated region 1 (C3CER1) in 3p21.3.

Occurrence of chromosome 3p deletions in a large number of human tumours suggests the existence of uncharted tumour suppressor gene(s). We previously applied a functional assay, named the Elimination test (Et), for the identification of regions containing tumour growth antagonising genes. This resulted in the definition of chromosome 3 common eliminated region 1 (C3CER1) on 3p21.3, which is regularly eliminated from SCID-derived tumours. Systematic genomic sequencing of 11 PAC clones, combined with comparisons of genomic sequence against EST databases and PCR-based cloning of cDNA sequences allowed us to assemble a comprehensive transcriptional map of 1.4 Mb that includes 19 active genes and three processed pseudogenes. We report four novel genes: FYVE and coiled-coil domain containing 1 (FYCO1), transmembrane protein 7 (TMEM7), leucine-rich repeat-containing 2 (LRRC2) and leucine zipper protein 3 (LUZP3). A striking feature of C3CER1 is a presence of a cluster of eight chemokine receptor genes. Based on a new analysis of the microcell hybrid-derived panel of SCID tumours we also redefined the centromeric border of the C3CER1. It is now located within LRRC2 gene, which is a relative of RSP-1 (Ras Suppressor Protein 1). The detailed knowledge of gene content in C3CER1 is a prerequisite for functional analysis of these genes and understanding of their possible role in tumorigenesis.