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, T.H.; Durant, John R.; Glickson, Jerry D.

doi:10.1016/0730-725x(84)90147-4

Cited by 12 publications

(15 citation statements)

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“…A low hypoxic fraction (c. 1-5%) has been previously measured in RIF-I tumours (Moulder and Rockwell, 1984;Maxwell et al, 1989 (Warren, 1979;Jain and Ward-Hartley, 1984 (Bhujwalla, 1988;Rofstad et al, 1988a), other transplanted tumours (Ng et al, 1982;Evanochko et al, 1984;Okunieff et al, 1986;Vaupel et al, 1989b) and human tumour xenografts (Rofstad et al, 1988b). A significant decrease of pH with tumour growth was only found for the faster growing RIF-1 and T404 tumours.…”

Section: Discussion Study 1: Unperturbed Growthmentioning

confidence: 75%

“…Previous reports suggest that the decline in bioenergetic status with tumour growth is consistent with the tumour vasculature becoming incapable of providing a nutritive blood supply to the rapidly expanding tissue (Ng et al, 1982;Evanochko et al, 1984;Okunieff et al, 1986;Bhujwalla, 1988;Rofstad et al, 1988a;Vaupel et al, 1989b). This results in a decrease in average cellular oxygen concentrations and the development of hypoxic tissue.…”

Section: Discussion Study 1: Unperturbed Growthmentioning

confidence: 92%

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31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models

Robinson

Boogaart²,

Maxwell³

et al. 1998

Br J Cancer

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Summary The objective of this study was first to determine whether three slowly growing early-generation murine transplantable tumours, the T40 fibrosarcoma, Ti 15 mammary carcinoma and T237 lung carcinoma, exhibit patterns of energetics and blood flow during growth that are different from those of the faster growing RIF-1 fibrosarcoma. Serial measurements were made with 31P-magnetic resonance spectroscopy (MRS), relating to nutritive blood flow and 2H-magnetic resonance imaging (MRI), which is sensitive to both nutritive and largevessel (non-nutritive) flow. All four tumour lines showed a decrease in fiNTP/Pi and pH with growth; however, each line showed a different pattern of blood flow that did not correlate with the decrease in energetics. Qualitative histological analysis strongly correlated with the 2H-MRI. Second, their response to 5 mg kg-' hydralazine i.v. was monitored by 31P-MRS. A marked decrease in f3NTP/Pi and pH was observed in both the RIF-1 fibrosarcoma and the third-generation T115 mammary carcinoma after hydralazine challenge. In contrast, the fourth generation T40 fibrosarcoma and T237 lung carcinoma showed no change in 31P-MRS parameters. However, a fifth-generation T237 cohort, which grew approximately three times faster than fourth-generation T237 cohorts, exhibited a significant deterioration in PNTP/Pi and pH in response to hydralazine. These data are consistent with a decoupling between large-vessel and nutritive blood flow and indicate that earlygeneration transplants that have a slow growth rate and vascular tone are more appropriate models of human tumour vasculature than more rapidly growing, repeatedly transplanted tumours.

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Section: Discussion Study 1: Unperturbed Growthmentioning

confidence: 75%

Section: Discussion Study 1: Unperturbed Growthmentioning

confidence: 92%

31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models

Robinson

Boogaart²,

Maxwell³

et al. 1998

Br J Cancer

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“…The potential utility of in vivo magnetic resonance spectroscopy (MRS) for detection of therapeutic response of cancers has been explored by a number of investigators (9)(10)(11)(12)(13)(14)(15)(16)(17). In vivo 1 H MRS detects a number of tumor phospholipid and bioenergetic metabolites associated with cell proliferation or degradation (9,14,18,19).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Monitoring Response to Chemotherapy of Human Diffuse Large B-Cell Lymphoma Xenografts in SCID Mice by 1H and 31P MRS

Huang¹,

Nelson²,

Pickup³

et al. 2007

Academic Radiology

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Rationale and Objectives-A reliable non-invasive method for in vivo detection of early therapeutic response of non-Hodgkin's lymphoma (NHL) patients would be of great clinical value. This study evaluates the feasibility of 1 H and 31 P magnetic resonance spectroscopy (MRS) for in vivo detection of response to combination chemotherapy of human diffuse large B-cell lymphoma (DLCL2) xenografts in SCID mice.Materials and Methods. C-ombination chemotherapy with Cyclophosphamide, Hydroxydoxorubicin, Oncovin, Prednisone, and Bryostatin 1 (CHOPB) was administered to tumorbearing SCID mice weekly for up to four cycles. Spectroscopic studies were performed before the initiation of treatment and after each cycle of the CHOPB. Proton MRS for detection of lactate and total choline was performed using a selective multiple-quantum-coherence-transfer (Sel-MQC) and a spin-echo-enhanced Sel-MQC (SEE-Sel-MQC) pulse sequence, respectively. Phosphorus-31 MRS utilizing a non-localized single-pulse sequence without proton decoupling was performed on these animals.Results-Significant decreases in lactate and total choline were detected in the DLCL2 tumors after one cycle of CHOPB chemotherapy. The ratio of phosphomonoesters to β-nucleoside triphosphate (PME/βNTP, measured by 31 P MRS) significantly decreased in the CHOPB treated tumors after two cycles of CHOPB. The control tumors did not exhibit any significant changes in either of these metabolites.Conclusions-This study demonstrates that 1 H MRS and 31 P MRS can detect in vivo therapeutic response of NHL tumors and that lactate and choline offer a number of advantages over PMEs as markers of early therapeutic response.

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“…The paradoxical increase in NTP and PCr after chemotherapy in HT-29 human colon cancer cells 2 h after exposure to 104 M doses of nitrogen mustard resembles increases in NTP observed at varying times in other systems with a variety of DNA-damaging agents including doxorubicin, cyclophosphamide, cisplatin and BCNU (Ng et al, 1982;Cohen et al, 1987;Werhle et al, 1987;Steen, 1989;Neeman et al, 1990;Berghmans et al, 1992). Steen has coined the term 'cellular activation' to describe this phenomenon (Steen, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…In 31p MRS spectra of regressing tumours in vivo, a frequent observation was a reduction in the ratio of high-energy to inorganic phosphate (ATP/Pi) (Evanochko, 1984;Naruse et al, 1985;Glickson et al, 1987;Smith et al, 1991), as might be expected with cells whose vital functions have been disrupted. However, other 31p MRS studies (Cohen et al, 1987;Werhle et al, 1987;Steen, 1989;Neeman et al, 1990;Berghmans et al, 1992;Ng et al, 1982) showed paradoxical increases in ATP/Pi or ATP posttreatment/ATP pretreatment peak ratios. These changes were observed from a few minutes to 16 h after drug administration, in both small and large tumours, animal and human tumours, in vitro and in vivo, and after administration of a variety of drugs, including doxorubicin, cyclophosphamide, cisplatin and BCNUeach of which in some way affects DNA structure.…”

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confidence: 97%

Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cells

Boddie

Constantinou²,

Williams³

et al. 1998

Br J Cancer

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Summary We hypothesized that unexplained increases in nucleoside triphosphates (NTP) observed by 31 magnetic resonance spectroscopy (MRS) after treatment of tumours by DNA-damaging agents were related to chemotherapy-induced up-regulation of the bcl-2 gene and DNA damage prevention and repair processes. To test this hypothesis, we treated HT-29 cells with 10-4 M nitrogen mustard (HN2) and performed sequential perchloric acid extractions in replicate over 0-18 h. By reference to an intemal standard (methylene diphosphonic acid), absolute changes in 31P-detectable high-energy phosphates in these extracts were determined and correlated with changes in bcl-2 protein levels, cell viability, cell cycle, apoptosis and total cellular glutathione (GSH) (an important defence against DNA damage from alkylating agents). After HN2 administration, bcl-2 protein levels in the HT-29 cell line rose at 2 h. Cell viability declined to 25% within 18 h, but apoptosis measured using fluorescence techniques remained in the 1-4% range. Increased cell division was noted at 4 h. Two high-energy interconvertible phosphates, NTP (P < 0.006) and phosphocreatine (PCr) (P < 0.0002), increased at 2 h concurrently with increased levels of bcl-2 protein and glutathione. This study demonstrates that bcl-2 and glutathione are up-regulated by HN2 and links this to a previously unexplained 31p MRS phenomenon: increased NTP after chemotherapy.

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31P NMR spectroscopy of in vivo tumors

Cited by 12 publications

References 0 publications

31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models

31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models

In Vivo Monitoring Response to Chemotherapy of Human Diffuse Large B-Cell Lymphoma Xenografts in SCID Mice by 1H and 31P MRS

Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cells

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