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Noninvasive estimation of tumour viability in a xenograft model of human neuroblastoma with proton magnetic resonance spectroscopy (1H MRS).

Lindskog M, Kogner P, Ponthan F, Schweinhardt P, Sandstedt B, Heiden T, Helms G, Spenger C - Br. J. Cancer (2003)

Bottom Line: The spectroscopic findings were compared to tumour morphology, proliferation and viable tumour tissue fraction.The results showed that signals from choline (Cho)-containing compounds and mobile lipids (MLs) dominated the spectra.Higher ML/Cho ratios concomitant with pronounced histological changes were seen in spectra from tumours treated with the antiangiogenic drug TNP-470, compared to untreated control tumours (P<0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Woman and Child Health, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.

ABSTRACT
The aim of the study was to evaluate proton magnetic resonance spectroscopy ((1)H MRS) for noninvasive biological characterisation of neuroblastoma xenografts in vivo. For designing the experiments, human neuroblastoma xenografts growing subcutaneously in nude rats were analysed in vivo with (1)H MRS and magnetic resonance imaging at 4.7 T. The effects of spontaneous tumour growth and antiangiogenesis treatment, respectively, on spectral characteristics were evaluated. The spectroscopic findings were compared to tumour morphology, proliferation and viable tumour tissue fraction. The results showed that signals from choline (Cho)-containing compounds and mobile lipids (MLs) dominated the spectra. The individual ML/Cho ratios for both treated and untreated tumours were positively correlated with tumour volume (P<0.05). There was an inverse correlation between the ML/Cho ratio and the viable tumour fraction (r=-0.86, P<0.001). Higher ML/Cho ratios concomitant with pronounced histological changes were seen in spectra from tumours treated with the antiangiogenic drug TNP-470, compared to untreated control tumours (P<0.05). In conclusion, the ML/Cho ratio obtained in vivo by (1)H MRS enabled accurate assessment of the viable tumour fraction in a human neuroblastoma xenograft model. (1)H MRS also revealed early metabolic effects of antiangiogenesis treatment. (1)H MRS could prove useful as a tool to monitor experimental therapy in preclinical models of neuroblastoma, and possibly also in children.

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Control spectra from skeletal muscle in a nude rat. The resonance of creatine/phosphocreatine (Cre) at 3.0 ppm was not detectable in neuroblastomas. Cho=choline, Lip=lipids. TE=20 ms, 64 averages.
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fig3: Control spectra from skeletal muscle in a nude rat. The resonance of creatine/phosphocreatine (Cre) at 3.0 ppm was not detectable in neuroblastomas. Cho=choline, Lip=lipids. TE=20 ms, 64 averages.

Mentions: Spectra from small xenografts (V<1.5 ml) typically had intense Cho signals together with moderate ML levels (Figure 1b). A small peak at 3.0 ppm, compatible with creatine/phosphocreatine, seemed to be present in most tumours but could not be unequivocally separated from Cho and was therefore not analysed further. The putative neuronal marker NAA (N-acetyl-aspartate) (Urenjak et al, 1992) with a chemical shift of 2.0 ppm was not distinguishable at short TEs where lipid signals overlapped with this spectral region. Neither intermediate (TE=135 ms) nor long (TE=172 ms) TEs (where lipid signals are fully relaxed) could support any presence of NAA in the xenografts (Figure 2). Spectra obtained from large tumours (V>2 ml) generally displayed a ML peak of high intensity at 1.2–1.4 ppm, a variable lipid peak at 0.9 ppm and a less prominent Cho signal (Figure 1 and Figure 2). Control spectra obtained from skeletal muscle showed a prominent creatine peak (only weakly present in tumour spectra) and a modest Cho signal (Figure 3Figure 3


Noninvasive estimation of tumour viability in a xenograft model of human neuroblastoma with proton magnetic resonance spectroscopy (1H MRS).

Lindskog M, Kogner P, Ponthan F, Schweinhardt P, Sandstedt B, Heiden T, Helms G, Spenger C - Br. J. Cancer (2003)

Control spectra from skeletal muscle in a nude rat. The resonance of creatine/phosphocreatine (Cre) at 3.0 ppm was not detectable in neuroblastomas. Cho=choline, Lip=lipids. TE=20 ms, 64 averages.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747540&req=5

fig3: Control spectra from skeletal muscle in a nude rat. The resonance of creatine/phosphocreatine (Cre) at 3.0 ppm was not detectable in neuroblastomas. Cho=choline, Lip=lipids. TE=20 ms, 64 averages.
Mentions: Spectra from small xenografts (V<1.5 ml) typically had intense Cho signals together with moderate ML levels (Figure 1b). A small peak at 3.0 ppm, compatible with creatine/phosphocreatine, seemed to be present in most tumours but could not be unequivocally separated from Cho and was therefore not analysed further. The putative neuronal marker NAA (N-acetyl-aspartate) (Urenjak et al, 1992) with a chemical shift of 2.0 ppm was not distinguishable at short TEs where lipid signals overlapped with this spectral region. Neither intermediate (TE=135 ms) nor long (TE=172 ms) TEs (where lipid signals are fully relaxed) could support any presence of NAA in the xenografts (Figure 2). Spectra obtained from large tumours (V>2 ml) generally displayed a ML peak of high intensity at 1.2–1.4 ppm, a variable lipid peak at 0.9 ppm and a less prominent Cho signal (Figure 1 and Figure 2). Control spectra obtained from skeletal muscle showed a prominent creatine peak (only weakly present in tumour spectra) and a modest Cho signal (Figure 3Figure 3

Bottom Line: The spectroscopic findings were compared to tumour morphology, proliferation and viable tumour tissue fraction.The results showed that signals from choline (Cho)-containing compounds and mobile lipids (MLs) dominated the spectra.Higher ML/Cho ratios concomitant with pronounced histological changes were seen in spectra from tumours treated with the antiangiogenic drug TNP-470, compared to untreated control tumours (P<0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Woman and Child Health, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.

ABSTRACT
The aim of the study was to evaluate proton magnetic resonance spectroscopy ((1)H MRS) for noninvasive biological characterisation of neuroblastoma xenografts in vivo. For designing the experiments, human neuroblastoma xenografts growing subcutaneously in nude rats were analysed in vivo with (1)H MRS and magnetic resonance imaging at 4.7 T. The effects of spontaneous tumour growth and antiangiogenesis treatment, respectively, on spectral characteristics were evaluated. The spectroscopic findings were compared to tumour morphology, proliferation and viable tumour tissue fraction. The results showed that signals from choline (Cho)-containing compounds and mobile lipids (MLs) dominated the spectra. The individual ML/Cho ratios for both treated and untreated tumours were positively correlated with tumour volume (P<0.05). There was an inverse correlation between the ML/Cho ratio and the viable tumour fraction (r=-0.86, P<0.001). Higher ML/Cho ratios concomitant with pronounced histological changes were seen in spectra from tumours treated with the antiangiogenic drug TNP-470, compared to untreated control tumours (P<0.05). In conclusion, the ML/Cho ratio obtained in vivo by (1)H MRS enabled accurate assessment of the viable tumour fraction in a human neuroblastoma xenograft model. (1)H MRS also revealed early metabolic effects of antiangiogenesis treatment. (1)H MRS could prove useful as a tool to monitor experimental therapy in preclinical models of neuroblastoma, and possibly also in children.

Show MeSH
Related in: MedlinePlus