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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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(A,C) Proton density-weighted MR images of two representative xenografts two (A) and three (C) weeks after cell inoculation, respectively. Scale bars=10 mm. (B) 1H MRS spectrum from tumour in A. The selected VOI is indicated by a rectangle. Cho-containing compounds dominate the spectrum. ML signals are also seen. TE=20 ms, 128 averages. (D) 1H MRS spectrum from large tumour seen in C. The VOI (rectangle in C) includes tumour tissue with variable signal intensity. There is a weak Cho signal while MLs dominate. TE=20 ms, 128 averages. B and D are not shown to scale.
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fig1: (A,C) Proton density-weighted MR images of two representative xenografts two (A) and three (C) weeks after cell inoculation, respectively. Scale bars=10 mm. (B) 1H MRS spectrum from tumour in A. The selected VOI is indicated by a rectangle. Cho-containing compounds dominate the spectrum. ML signals are also seen. TE=20 ms, 128 averages. (D) 1H MRS spectrum from large tumour seen in C. The VOI (rectangle in C) includes tumour tissue with variable signal intensity. There is a weak Cho signal while MLs dominate. TE=20 ms, 128 averages. B and D are not shown to scale.

Mentions: Tumours <1.5 ml generally appeared homogeneous but occasionally contained foci with low signal intensity on T2 images. Such low signal areas were seen more often in larger tumours. All tumours >2 ml had a heterogeneous appearance, containing both hyperintense and hypointense areas (Figure 1Figure 1


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)

(A,C) Proton density-weighted MR images of two representative xenografts two (A) and three (C) weeks after cell inoculation, respectively. Scale bars=10 mm. (B) 1H MRS spectrum from tumour in A. The selected VOI is indicated by a rectangle. Cho-containing compounds dominate the spectrum. ML signals are also seen. TE=20 ms, 128 averages. (D) 1H MRS spectrum from large tumour seen in C. The VOI (rectangle in C) includes tumour tissue with variable signal intensity. There is a weak Cho signal while MLs dominate. TE=20 ms, 128 averages. B and D are not shown to scale.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: (A,C) Proton density-weighted MR images of two representative xenografts two (A) and three (C) weeks after cell inoculation, respectively. Scale bars=10 mm. (B) 1H MRS spectrum from tumour in A. The selected VOI is indicated by a rectangle. Cho-containing compounds dominate the spectrum. ML signals are also seen. TE=20 ms, 128 averages. (D) 1H MRS spectrum from large tumour seen in C. The VOI (rectangle in C) includes tumour tissue with variable signal intensity. There is a weak Cho signal while MLs dominate. TE=20 ms, 128 averages. B and D are not shown to scale.
Mentions: Tumours <1.5 ml generally appeared homogeneous but occasionally contained foci with low signal intensity on T2 images. Such low signal areas were seen more often in larger tumours. All tumours >2 ml had a heterogeneous appearance, containing both hyperintense and hypointense areas (Figure 1Figure 1

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