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SUMMARY:Detecting early tumour responses to therapy using magnetic resonan
 ce imaging and hyperpolarized spectroscopy - Professor Kevin M. Brindle\, 
 Dept. of Biochemistry\, University of Cambridge
DTSTART:20071024T153000Z
DTEND:20071024T163000Z
UID:TALK8028@talks.cam.ac.uk
CONTACT:6490
DESCRIPTION:We have been developing non-invasive and clinically applicable
  magnetic resonance-based methods for detecting the early responses of tum
 ours to therapy.  A primary focus has been on the development of methods f
 or detecting tumour cell death\, since the level of tumour cell death imme
 diately after drug treatment has been shown\, in preclinical and clinical 
 studies\, to be a good prognostic indicator for treatment outcome.  Thus a
 n oncologist may get an indication of whether a particular drug is working
  very early during treatment\, possibly within 24-48 hours\, and long befo
 re there is any evidence of tumour shrinkage.\n\nThe primary focus of our 
 work has been the development of a targeted MRI contrast agent that binds 
 to dying cells and recent progress with this agent will be described.\n\nM
 ore recently\, we have started to work with dynamic nuclear polarization (
 DNP) of 13C-labelled cell substrates\, which offers gains in sensitivity o
 f more than 104-fold\, allowing sub second acquisition of 13C spectral dat
 a in vivo.  Using DNP MRSI we have studied the metabolism of hyperpolarize
 d [1-13C] pyruvate in an EL-4 lymphoma cells and in implanted EL-4 tumors\
 , before and after treatment with the chemotherapeutic drug\, etoposide. T
 here was a significant reduction in lactate dehydrogenase-catalyzed exchan
 ge of 13C label between pyruvate and lactate in tumors 24 h after drug tre
 atment.  Images of intratumoral 13C pyruvate and 13C lactate showed a mark
 ed reduction in intensity in lactate/pyruvate ratiometric images. The decr
 ease in exchange can be explained by a reduction in the lactate concentrat
 ion in the tumor\, a reduction in cellularity\, and possibly decreases in 
 intracellular coenzyme (NAD(H)) and lactate dehydrogenase concentrations. 
  The absence of any background 13C signal means that specific images of en
 zyme activity can be acquired. The lack of ionizing radiation\, the use of
  an endogenous metabolite and a single imaging modality makes DNP 13C MRI 
 an attractive potential tool for imaging the early responses of tumours to
  treatment in the clinic.\n
LOCATION:Lecture Theatre 1\, Department of Veterinary Medicine
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