Metabolic imaging in tumours by means of bioluminescence

Abstract

The development of metabolic imaging in normal or tumour tissue sections using bioluminescence detection makes it possible to study the relation between their histology and the spatial distribution of metabolites, e.g. ATP, glucose and lactate. Previous method usng photographic film for imaging these metabolites in normal brain and tumour sections (Hossmann et al., 1986;Paschen, 1990) were often very time consuming and not always reproducible owing to the poor resolution obtained. This drawback has been largly overcome through the introduction of high resolution single photon imaging (Muller-Kiieser et al., 1988), to the ectent that metabolite levels can be quantified in absolute values. This technique has clearly demonstrated that metabolites are distributed much more heterogeneously in tumours than in normal tissues, where the pattern is of a more homogeneous nature. This finding is not unexpected in view of the chaotic vasculature frequently seen within tumours (Konerding et al., 1989a, b). As a result, solid tumours often show areas with a restric blood perfusion and poor nutritve supply. Such regional differences may be of relevance to radiobioogical hypoxia in viable tumour areas. In addition, the use of biolumiescence can help to distinguish between viable and necrotic regions in tumours not possible with other conventional biochemical techniques. Such methods produce only average values for the whole tissue in question and are unable to give details as to their spatial distribution in the regions of interest or 'hotspots'.Since ghlcs metabolism is very important for energy production in tumours (Streffer, 1994), it was of interest to investigate possible correlations between the distribution of ghluose, lactate and ATP in a number of different tumour entities, including a squamous head and neck carcnoma, a melanoma, a rectum carcinoma and a murine mammary adenocarcinoma maintained as xenotransplants on nude mice using the novel methodology of photon imaging. We compared the metabolic distributions in cryosections from these xenotransplants with those in normal heart muscle. Materls aud mhodsTwnours All tumours were maintained as xenografts on nude mice (NMRI strain) as described previously (Steinberg et al.,

Growth as a solid tumor or reduced glucose concentrations in culture reversibly induce CD44-mediated hyaluronan recognition by Chinese hamster ovary cells.

“…Further study will be required to establish whether local glucose concentrations or some other aspect of the tumor environment induced HA recognition in CHO-K1 cells. However, the 250 g/ml (1.4 mM) concentration of glucose that was effective is one that can be achieved in hypoglycemia or within tumors (72,73). Interaction of cells with certain cytokines might have the opposite effect, i.e., reduce HA recognition via CD44.…”

Fatigue associated with cancer and its treatment

“…ATP concentrations may be relatively low in certain areas of tumors themselves [35, 65,66,111]. Compromised blood supply to tumors results in oxygen-depleted areas of the tumors, associated with deprivation of nutrients and energy and a hostile metabolic microenvironment (i.e.…”

Arimidex inhibition on proliferation of human breast solid tumors measured by ATP bioluminescence

“…(Harvey, 1998) Four fold to six fold higher estrogen levels are observed in tumors than in plasma of postmenopausal patients with breast cancer. (Tamulevicius and Streffer, 1995). Progesterone is an important regulator of growth in breast tissues as it controls cell division and differentiation.…”

“…(Harvey, 1998;Lake and Hudis, 2002;Spigel and Burstein, 2002) It provides a significant source of estrogen mediating tumor proliferation in postmenopausal women. Since intratumoral aromatase produces estrogen in situ, it is the target for successful inhibitor treatment (Tamulevicius and Streffer, 1995).…”