Purpose: Modern imaging technologies such as CT, PET, SPECT, and MRI employ contrast agents to visualize the tumor microenvironment, providing information on malignancy and response to treatment. Currently, all clinical imaging agents require chemical labeling, i.e. with iodine (CT), radioisotopes (PET/SPECT), or paramagnetic metals (MRI). The goal was to explore the possibility of using simple D‐glucose as an infusable biodegradable MRI agent for cancer detection.Methods: D‐glucose signals were detected using chemical exchange saturation transfer (glucoCEST) MRI of its hydroxyl groups. Feasibility was established in phantoms as well as in vivo using two human breast cancer cell lines, MDA‐MB‐231 and MCF‐7, implanted orthotopically in nude mice. PET and contrast‐enhanced MRI were also acquired.Results: Both tumor types exhibited significant glucoCEST signal enhancement during systemic sugar infusion (mild hyperglycemia), allowing their noninvasive visualization. GlucoCEST showed differences between types, while PET and CE‐MRI did not. Data are discussed in terms of signal contributions from the increased vascular volume in tumors and especially from the acidic extracellular extravascular space (EES), where glucoCEST signal is expected to be enhanced due to a slow down of hydroxyl proton exchange.Conclusions: This observation opens up the possibility for using simple non‐toxic sugars as contrast agents for cancer detection with MRI by employing hydroxyl protons as a natural label. Magn Reson Med, 2012.

Biocompatible nanomaterials and hydrogels have become an important tool for improving cell-based therapies by promoting cell survival and protecting cell transplants from immune rejection. Although their potential benefit has been widely evaluated, at present it is not possible to determine, in vivo, if and how long cells remain viable following their administration without the use of a reporter gene. Here, we report a pH-nanosensor-based magnetic resonance imaging (MRI) technique that can monitor cell death in vivo non-invasively. We demonstrate that specific MRI parameters that change on cell death of microencapsulated hepatocytes are associated with the measured bioluminescence imaging radiance. Moreover, the readout from this pH-sensitive nanosensor can be directly co-registered with high-resolution anatomical images. All of the components of these nanosensors are clinical grade and hence this approach should be a translatable and universal modification of hydrogels.

Recent animal studies have shown that D-glucose is a potential biodegradable magnetic resonance imaging (MRI) contrast agent for imaging glucose uptake in tumors. We show herein the first translation of that use of D-glucose to human studies. Chemical exchange saturation transfer (CEST) MRI at a single frequency offset optimized for detecting hydroxyl protons in D-glucose was used to image dynamic signal changes in the human brain at 7 T during and after D-glucose infusion. Dynamic glucose enhanced (DGE) image data from 4 normal volunteers and 3 glioma patients showed a strong signal enhancement in blood vessels, while a spatially varying enhancement was found in tumors. Areas of enhancement differed spatially between DGE and conventional gadolinium-enhanced imaging, suggesting complementary image information content for these 2 types of agents. In addition, different tumor areas enhanced with D-glucose at different times after infusion, suggesting a sensitivity to perfusion-related properties such as substrate delivery and blood-brain barrier (BBB) permeability. These preliminary results suggest that DGE MRI is feasible for studying glucose uptake in humans, providing a time-dependent set of data that contains information regarding arterial input function, tissue perfusion, glucose transport across the BBB and cell membrane, and glucose metabolism.

Noninvasive detection of exosomal MCT1/CD147 can monitor the progression of glioma, a fatal brain tumor, as a liquid biopsy.

Purpose Chemical exchange saturation transfer (CEST) imaging is a new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through their exchangeable protons. A new technique, variable delay multi‐pulse CEST (VDMP‐CEST), is proposed to eliminate the need for recording full Z‐spectra and performing asymmetry analysis to obtain CEST contrast. Methods The VDMP‐CEST scheme involves acquiring images with two (or more) delays between radiofrequency saturation pulses in pulsed CEST, producing a series of CEST images sensitive to the speed of saturation transfer. Subtracting two images or fitting a time series produces CEST and relayed‐nuclear Overhauser enhancement CEST maps without effects of direct water saturation and, when using low radiofrequency power, minimal magnetization transfer contrast interference. Results When applied to several model systems (bovine serum albumin, crosslinked bovine serum albumin, l‐glutamic acid) and in vivo on healthy rat brain, VDMP‐CEST showed sensitivity to slow to intermediate range magnetization transfer processes (rate < 100–150 Hz), such as amide proton transfer and relayed nuclear Overhauser enhancement‐CEST. Images for these contrasts could be acquired in short scan times by using a single radiofrequency frequency. Conclusions VDMP‐CEST provides an approach to detect CEST effect by sensitizing saturation experiments to slower exchange processes without interference of direct water saturation and without need to acquire Z‐spectra and perform asymmetry analysis. Magn Reson Med 71:1798–1812, 2014.