In vivo³¹P MRS of experimental tumours

Abstract

More than 50% of cancers fail to respond to any individual treatment and tumour follow-up after treatment plays a major role in routine therapy planning and pharmacological research. Today, MRS is the only technological approach providing non-invasive access to tumour biochemistry. Ten years ago, expectations were raised concerning 31P MRS as an exciting and promising technical approach to the study of tumours. However the expectations have not always come to fruition. How close are we now to seeing routine 31P NMR in clinical oncology? This review of the 127 published papers shows spectroscopy results in more than 150 experimental animal tumour models. These tumour/host/treatment systems provide us with a useful basis to evaluate the current state of the art, summarize the basic knowledge presently available, determine the key points underlying the present disappointment of some clinical oncologists and stimulate new basic research. The information collected concerns the discussion of the reliability of experimental models in oncology, the technical improvement of magnetic resonance technology and the monitoring of bioenergetic status, pH regulation and phospholipid metabolism in treated and untreated tumours. Recent advances (two-thirds of the papers have been published in the last 5 years) seem to provide more optimistic perspectives than those generally accepted a few years ago, in the depressing period following early pioneering work.

Choline Kinase Is a Novel Oncogene that Potentiates RhoA-Induced Carcinogenesis

“…Furthermore, choline kinase activation is associated with variable indicators of greater malignancy in breast tumors (2). Consistent with these findings, nuclear magnetic resonance techniques have shown elevated levels of phosphorylcholine in human tumoral tissues with respect to their normal counterparts (3,4), whereas choline kinase is activated by several growth factors (5,6) and oncogenes (7)(8)(9)(10). All these observations constitute the basis of the design of a new antitumoral strategy focused on specifically interfering with choline kinase activity.…”

Inhibition of choline kinase as a specific cytotoxic strategy in oncogene-transformed cells

“…A glycerophosphocholine (GPC) to PCho switch appeared to be an early phenotypic change during carcinogenesis, independent of cell-doubling time and without differences in high-energy phosphates, rates of glucose consumption and aerobic glycolysis (Ting et al, 1996;Aboagye and Bhujwalla, 1999). Additional NMR studies also find high levels of phosphomonoesters (PCho and/or PEtn) in tumors when compared to the corresponding normal tissues (de Certaines et al, 1993;Smith et al, 1993;Bhakoo et al, 1996). Finally, increased ChoK activity has been demonstrated in human tumors (Ramirez de Molina et al, 2002a, c), and a functional relationship between Ras proteins and ChoK has been established (Ramirez de Molina et al, 2002b).…”

18F-fluorocholine for prostate cancer imaging: a systematic review of the literature

“…15,16 Alterations in choline metabolism have been demonstrated to be a common metabolic change in many cancers and are thought to reflect increased demands from proliferating cancer cells, but also may reflect changes in alterations in choline uptake and retention due to alterations in choline transport and the activity of choline kinase. [17][18][19] When labeled with 11 C, both choline and acetate substrates can be used to image PCa with PET and PET/CT. 11 C-acetate and 11 C-choline PET have been reported to be more sensitive than 18 F-FDG PET in the detection of primary lesions, regional lymph node and bone metastases.…”