Noninvasive real-time monitoring of intracellular cancer cell metabolism and response to lonidamine treatment using diffusion weighted proton magnetic resonance spectroscopy
Y. Mardor et al., Noninvasive real-time monitoring of intracellular cancer cell metabolism and response to lonidamine treatment using diffusion weighted proton magnetic resonance spectroscopy, CANCER RES, 60(18), 2000, pp. 5179-5186
We have used diffusion-weighted proton magnetic resonance spectroscopy (DWM
RS) to noninvasively selectively observe only the intracellular metabolites
of breast cancer and melanoma cell lines irt vitro in real time. Breast ca
ncer cell lines representing different stages in breast cancer progression
were chosen for study. Intracellular biochemical profiles of six cell lines
perfused in alginate beads were obtained, Spectral differences between gro
ups of cell lines, including choline, lactate, and threonine peaks, were in
vestigated, We also monitored response to the antineoplastic agent, lonidam
ine (LND), as a function of time and drug concentration in perfused cancer
cells. Previous studies reported that this drug induced intracellular acidi
fication and lactate accumulation. Diffusion weighted proton spectra demons
trated a 2- to 9-fold increase in the intracellular lactate signal as a res
ponse to LND treatment in several cancer cell lines. These results are cons
istent,vith the hypothesis that the principal mechanism of LM) in some canc
er cells is marked inhibition of lactate transport. Moreover, we have shown
that there is a factor of two to three between the response of melanoma ce
lls and that of some types of breast cancer cells. The higher sensitivity o
f the melanoma cells, as predicted by proton DWMRS, was correlated with cha
nges in water-suppressed magnetic resonance spectra and confirmed by a biol
ogical assay. This study demonstrates the feasibility of using DWMRS for mo
nitoring intracellular metabolism and for studying the effects and mechanis
ms of action of anticancer drugs, We believe that this method can be used f
or noninvasive clinical applications, such as the differentiation between b
enign and malignant tissue, real-time monitoring of response to therapy, do
se response, and toxicity effects.