31P NMR spectroscopy of in vivo tumors

Ng, Thian C.; Evanochko, William T.; Hiramoto, Raymond N.; Ghanta, Vithal K.; Lilly, Michael B.; Lawson, Alfred J.; Corbett, Thomas H.; Durant, John R.; Glickson, Jerry D.

doi:10.1016/0022-2364(82)90190-1

Cited by 106 publications

(38 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ovariectomy in animals bearing NMU induced mammary adenocarcinomas caused the phosphorous metabolite ratios (PCr/ NTP, PCr/Pi and NTP/Pi) to increase . These increases may be analogous to a similar rise that has been observed after chemotherapy (Ng et al, 1982, Steen et al, 1988. The underlying mechanism of both these changes is unclear.…”

supporting

confidence: 66%

“…Most therapeutic modalities, including chemotherapy (Evanochko et al, 1984; Steen et al, 1988) and irradiation (Tozer et al, 1989), perturb the energy metabolism of tumours. We have previously shown that in the untreated N-methyl-N-nitrosourea (NMU) induced mammary tumour, high energy phosphates are lost with increasing tumour size , a change that has been seen in other animal tumours (Ng et al, 1982). Ovariectomy in animals bearing NMU induced mammary adenocarcinomas caused the phosphorous metabolite ratios (PCr/ NTP, PCr/Pi and NTP/Pi) to increase .…”

mentioning

confidence: 97%

See 1 more Smart Citation

31P-NMR spectroscopy and histological studies of the response of rat mammary tumours to endocrine therapy

Stubbs

Coombes²,

Griffiths³

et al. 1990

Br J Cancer

View full text Add to dashboard Cite

Summary We have shown by 3'P-NMR spectroscopy that ovariectomy, in N-methyl-N-nitrosourea induced mammary adenocarcinomas, increases signals from phosphocreatine (PCr) relative to nucleoside triphosphate (NTP) before measurable regression (2 days) and for at least a further 13 days. The present study correlates the NMR changes with histological changes in the regressing tumour. Mammary tumours were examined by NMR before, and 2 and 14 days after, ovariectomy or sham-ovariectomy. Sections were taken from five tumours at each time point after operation for histology and for immunocytochemical staining of myoepithelial cells, luminal cells and basement membrane material. The histology showed typical cribriform papillary type mammary adenocarcinomas. The luminal cell population had a high mitotic activity and there was a prominent myoepithelial layer. At 2 days post-ovariectomy no significant change in mitotic activity was observed and no cytological characteristics attributable to ovariectomy could be seen. At 14 days postovariectomy the tumour was indistinguishable from a tubular adenoma, had significantly reduced mitotic activity, a relative increase in myoepithelial cells and basement membrane material. The changes detected by NMR must reflect early metabolic events, perhaps related to the histological changes observed at 14 days after ovariectomy. 31P-NMR spectroscopy may permit early monitoring of endocrine therapy for mammary cancer.3'P-NMR is a non-invasive technique that can be used for monitoring the energetics of tumours in situ either in animals or in patients. Among other metabolities it detects the high energy phosphate compounds, nucleoside triphosphate (NTP) and phosphocreatine (PCr) and their breakdown product, inorganic phosphate (Pi). Most therapeutic modalities, including chemotherapy (Evanochko et al., 1984; Steen et al., 1988) and irradiation (Tozer et al., 1989), perturb the energy metabolism of tumours. We have previously shown that in the untreated N-methyl-N-nitrosourea (NMU) induced mammary tumour, high energy phosphates are lost with increasing tumour size , a change that has been seen in other animal tumours (Ng et al., 1982). Ovariectomy in animals bearing NMU induced mammary adenocarcinomas caused the phosphorous metabolite ratios (PCr/ NTP, PCr/Pi and NTP/Pi) to increase . These increases may be analogous to a similar rise that has been observed after chemotherapy (Ng et al., 1982, Steen et al., 1988. The underlying mechanism of both these changes is unclear. In particular, do they reflect alterations in cell populations (infiltration by host cells, replacement of one tumour cell type by another etc.) or are they predominantly due to alterations in the metabolism of the cells that were present at the start of therapy? It seems clear that changes in cell populations must, at least in some cases, cause changes in the NMR spectrum, but these changes would probably take several days. If metabolic alterations in the original cancer cells can also change tumour high energy phosphates the...

show abstract

supporting

confidence: 66%

mentioning

confidence: 97%

31P-NMR spectroscopy and histological studies of the response of rat mammary tumours to endocrine therapy

Stubbs

Coombes²,

Griffiths³

et al. 1990

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…As a NMR spectrometer transmits a rf pulse, it should be possible to produce hyperthermia using the rf pulse generated by the spectrometer in the magnet. It is also supposed that the effects so produced could be monitored sensitively with the same spectrometer by 31P NMR spectrum measurements as in other therapies (2)(3)(4)(5). Therefore, we intended to generate rf hyperthermia on experimental tumors using the NMR spectrometer with successive monitoring of the effects in the same device in an attempt to find a further application of NMR as well as to obtain informative data for hyperthermia as a cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Radiofrequency hyperthermia with successive monitoring of its effects on tumors using NMR spectroscopy.

Shoji¹,

Higuchi²,

Horikawa³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Radiofrequency (rf) hyperthermia was generated on rat glioma inoculated s.c. in CD Fisher rats by applying the rf pulse using the surface coil in the NMR spectrometer, and the effect was monitored successively in the same spectrometer by measuring 31p NMR spectra and 'H NMR images. In the 31P NMR spectrum at the preirradiation stage, nucleoside triphosphate peaks and a phosphomonoester peak were high and a Pi peak was low. After a rf pulse at a power of 5 W was applied continuously for 60 min, the nucleoside triphosphate peaks decreased and the Pi peak increased immediately, resulting finally in a dominant Pi peak pattern within 30 min in all 10 cases ened. These spectral changes occurred much earlier than the histological changes and lasted for at least 7 days. By the 1H NMR imaging, the necrotic region was detected as a high-intensity lesion in spin echo and inversion recovery images 2 days after the irradiation. There were no changes either in the spectrum or in 1H NMR images in any of 8 cases after irradiation with a rf pulse of <3 W. Thus, we could generate rf hyperthermia with the NMR spectrometer and the effects were monitored sensitively with the same spectrometer. It can be concluded that the NMR device can be used not only for diagnosis but also. as a therapeutic tool.Radiofrequency (rf) hyperthermia is a matter of concern in cancer treatment (1). Though the mechanism and effects of this therapy have been studied extensively, many problems have been left unsolved-for example, the appropriate power of the rf pulse, proper duration of heating, proper design of the rf coil, effectiveness ofcombined therapy, and so on. This is partly due to the lack of an appropriate method for examining the mechanism and for evaluating the effect of the treatment in vivo. Meanwhile, there has been recent, rapid progress in the application ofNMR to the medical field. In the course of looking for new applications ofthe NMR method to the medical field, we took notice of generating rf hyperthermia using a NMR spectrometer. As a NMR spectrometer transmits a rf pulse, it should be possible to produce hyperthermia using the rf pulse generated by the spectrometer in the magnet. It is also supposed that the effects so produced could be monitored sensitively with the same spectrometer by 31P NMR spectrum measurements as in other therapies (2)(3)(4)(5). Therefore, we intended to generate rf hyperthermia on experimental tumors using the NMR spectrometer with successive monitoring of the effects in the same device in an attempt to find a further application of NMR as well as to obtain informative data for hyperthermia as a cancer therapy. MATERIALS AND METHODSExperimental Animals. A total of 54 CD Fisher rats was used for the experiments. A suspension of 106_107 cultured rat glioma (EA285) cells was inoculated s.c. in the lumbar region of the animal (2). Twenty-eight days after inoculating the tumor cells, when the tumors grew to >1.5 cm in diameter, the animals were divided into two groups-a control group and the rf hyperther...

show abstract

“…Surface coil 31P-NMR spectra of subcutaneously grown or induced tumours in the rat represent a slowly changing steady state as the tumour increases in size. We conclude that increasing numbers of hypoxic tumour cells, rather than large areas of necrotic tissue, contribute largely to the NMR spectrum.3'P-NMR spectroscopy has been used to monitor growth and response to therapy in several experimental tumour lines (Ng et al, 1982; Steen et al, 1988;Wehrle et al, 1987;Rodrigues et al, 1988;Tozer et al, 1989). Tumour response to various types of chemotherapy and X-irradiation therapy often involves the reversal of the changes seen during untreated progression; the treated tumour appears more highly energised (i.e.…”

mentioning

confidence: 99%

“…Most tumours described in the literature have shown a fall in high energy phosphates with increasing age and size which is usually attributed to increasing hypoxic or necrotic fractions (Ng et al, 1982;Rofstad et al, 1988a). Other factors, such as host cell invasion, oedema, haemorrhage and cyst formation, will also affect the spectrum.…”

mentioning

confidence: 99%

Growth studies of subcutaneous rat tumours: comparison of 31P-NMR spectroscopy, acid extracts and histology

Stubbs

Rodrigues²,

Griffiths³

1989

Br J Cancer

View full text Add to dashboard Cite

Summary 31P-NMR surface coil spectra of three subcutaneously implanted rat tumours (Morris hepatoma 7777, GH3 prolactinoma, Walker carcinosarcoma) and an N-methyl-N-nitrosourea induced rat mammary adenocarcinoma at different stages of growth were obtained and compared with histological sections taken immediately after NMR acquisitions. Metabolite ratios (phosphocreatine (PCr)/Pnucleoside triphosphate (PNTP), PCr/Pi, PNTP/Pi) calculated from the NMR spectra were compared with ratios obtained from acid extracts of tumours of similar size. Measurements of creatine and ADP were also made. Three of the tumours showed positive correlations between increasing tumour size and decreasing metabolite ratios measured both by NMR and in extracts, whereas the Walker carcinosarcoma showed no correlation between size and any parameters measured. Phosphorus metabolite ratios, measured in extracts of skin overlying the tumours, indicated a fall in high energy phosphate when there was histological evidence of skin invasion by the tumour. Surface coil 31P-NMR spectra of subcutaneously grown or induced tumours in the rat represent a slowly changing steady state as the tumour increases in size. We conclude that increasing numbers of hypoxic tumour cells, rather than large areas of necrotic tissue, contribute largely to the NMR spectrum.3'P-NMR spectroscopy has been used to monitor growth and response to therapy in several experimental tumour lines (Ng et al., 1982; Steen et al., 1988;Wehrle et al., 1987;Rodrigues et al., 1988;Tozer et al., 1989). Tumour response to various types of chemotherapy and X-irradiation therapy often involves the reversal of the changes seen during untreated progression; the treated tumour appears more highly energised (i.e. has increased phosphocreatine/pnucleoside triphosphate (PCr/PNTP), PCr/Pi or PNTP/Pi; see Methods) than before treatment.The changes in the 3'P-NMR spectra that occur as animal tumours grow could be due to several causes. Most tumours described in the literature have shown a fall in high energy phosphates with increasing age and size which is usually attributed to increasing hypoxic or necrotic fractions (Ng et al., 1982;Rofstad et al., 1988a). Other factors, such as host cell invasion, oedema, haemorrhage and cyst formation, will also affect the spectrum.Our recent studies (Stubbs et al., 1988a(Stubbs et al., , 1989 on the contribution of rat skin to surface coil spectra of subcutaneous tumours suggest that this, too, could be important in studies on animals.If the tumour invades and destroys the skin (and particularly the panniculus carnosus muscle which forms a major part of rodent skin) the skin contribution to the 3'P-NMR spectrum will decrease with increasing tumour size. In order to elucidate these processes we have embarked on a series of studies of tumour growth.Here we report the results of NMR studies of a variety of subcutaneously implanted rat tumours in vivo, at different time points in their growth, where we have compared the NMR spectra with histological sections of the t...

show abstract

31P NMR spectroscopy of in vivo tumors

Cited by 106 publications

References 18 publications

31P-NMR spectroscopy and histological studies of the response of rat mammary tumours to endocrine therapy

31P-NMR spectroscopy and histological studies of the response of rat mammary tumours to endocrine therapy

Radiofrequency hyperthermia with successive monitoring of its effects on tumors using NMR spectroscopy.

Growth studies of subcutaneous rat tumours: comparison of 31P-NMR spectroscopy, acid extracts and histology

Contact Info

Product

Resources

About