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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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Significant inverse correlation between ML/Cho-ratio and viable tumour fraction in human neuroblastoma xenografts (r=−0.86, P<0.001) (data pooled from TNP and control groups).
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fig6: Significant inverse correlation between ML/Cho-ratio and viable tumour fraction in human neuroblastoma xenografts (r=−0.86, P<0.001) (data pooled from TNP and control groups).

Mentions: The ML/Cho ratio was significantly correlated with tumour volume for both treated and untreated tumours (r=0.75, P<0.05 and r=0.73, P<0.05, respectively) (Figure 5A). In the treatment group ML/Cho ratios increased faster with tumour volume than in untreated animals (P<0.05). Viable tumour fraction was negatively correlated to tumour volume in untreated animals (r=0.88, P<0.001) (Figure 5B). In treated animals there was a tendency towards a similar correlation (P=0.058). Comparison with histological findings revealed a significant inverse correlation between the ML/Cho ratio and the viable tumour cell fraction (r=−0.86, P<0.001) (Figure 6Figure 6


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)

Significant inverse correlation between ML/Cho-ratio and viable tumour fraction in human neuroblastoma xenografts (r=−0.86, P<0.001) (data pooled from TNP and control groups).
© Copyright Policy
Related In: Results  -  Collection

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

fig6: Significant inverse correlation between ML/Cho-ratio and viable tumour fraction in human neuroblastoma xenografts (r=−0.86, P<0.001) (data pooled from TNP and control groups).
Mentions: The ML/Cho ratio was significantly correlated with tumour volume for both treated and untreated tumours (r=0.75, P<0.05 and r=0.73, P<0.05, respectively) (Figure 5A). In the treatment group ML/Cho ratios increased faster with tumour volume than in untreated animals (P<0.05). Viable tumour fraction was negatively correlated to tumour volume in untreated animals (r=0.88, P<0.001) (Figure 5B). In treated animals there was a tendency towards a similar correlation (P=0.058). Comparison with histological findings revealed a significant inverse correlation between the ML/Cho ratio and the viable tumour cell fraction (r=−0.86, P<0.001) (Figure 6Figure 6

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