Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy in a murine tumour in vivo.
Nuclear magnetic resonance (NMR) non-invasively measures the apparent diffusion coefficient (ADC) of water, which is sensitive to the biophysical characteristics of tissue. Because anti-cancer treatment alters tumour pathophysiology, tumour ADC may be altered by treatment. In order to test this hypothesis, ADC was measured in s.c. implanted murine RIF-1 tumours before and up to 9 days after treatment with cyclophosphamide. A dose-dependent, reversible increase in tumour ADC was observed after cyclophosphamide treatment, which is consistent with an increase in the fraction of interstitial water due to treatment-induced cell death. Because tumour water ADC is increased substantially at a time when there is no change in tumour volume for a dose which produces minimal cell kill, its measurement could provide a novel means for early detection of response to anti-cancer therapy. If the changes in ADC observed in the present study are evident for commonly used anti-cancer therapies in different tumour types and specific to a therapeutic response, the approach could be broadly applicable as a response predictor since magnetic resonance imaging can be used to measure ADC in human tumours.
Zhao
M
M
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Pipe
J G
JG
Bonnett
J
J
Evelhoch
J L
JL
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002463:Cell Membrane Permeability; D003520:Cyclophosphamide / Q000494:pharmacology; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D005354:Fibrosarcoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D011522:Protons; D014867:Water / Q000378:metabolism*
D018906:Antineoplastic Agents, Alkylating; D011522:Protons; D014867:Water; D003520:Cyclophosphamide