Natural D-glucose as a biodegradable MRI contrast agent for detecting cancer.
OBJECTIVE
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.
Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kannie W Y
KW
Chan
Michael T
MT
McMahon
Yoshinori
Y
Kato
Guanshu
G
Liu
Jeff W M
JW
Bulte
Zaver M
ZM
Bhujwalla
Dmitri
D
Artemov
Peter C M
PC
van Zijl
D020341:Absorbable Implants; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D005240:Feasibility Studies; D005260:Female; D005947:Glucose; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D003287:Contrast Media; D005947:Glucose