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

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 (Po0.05). There was an inverse correlation between the ML/Cho ratio and the viable tumour fraction (r ¼ À0.86, Po0.001). 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 (Po0.05). 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.

Cyclooxygenase-2 Is Expressed in Neuroblastoma, and Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Tumor Growth In vivo

“…Moreover, 1 H MRS typically shows increased content of PUFAs and methylene groups of mobile lipids in cancer cells undergoing therapy-induced cell death (7,9). We therefore investigated the possibility of monitoring the levels of PUFAs with 1 H MRS in neuroblastoma cells treated with NSAIDs.…”

Quantification of phosphocholine and glycerophosphocholine with31P edited1H NMR spectroscopy

“…11 However, one of the most studied connections has been with cancer. [12][13][14][15][16][17][18] In general, the concentrations of choline-compounds are elevated in cancer and, more importantly, ex vivo studies of tissue extract samples suggest that the ratio of the phosphoryl derivatives indicates the status of the disease. [19][20][21] The signals of the methyl [-N(CH 3 ) 3 ] protons has been used to differentiate choline (3.185 ppm) from PC (3.208 ppm) and GPC (3.212 ppm) in ex vivo analyses.…”

Oncoproteomics of Neuroblastoma: A Blueprint for Future Progress

“…This technologic platform is quickly becoming an expanding area of cancer research as it has the applicability to aid in tumor diagnosis through the discovery of new markers, improve taxonomic classification by generating accurate metabolic tumor profiles, and aid in the identification of novel anti-cancer targets and screening of compounds for anti-proliferative effects [96]. With respect to NB, proton magnetic resonance spectroscopy ( 1 H-MRS) has been demonstrated to estimate in vivo tumor viability and response to various chemotherapeutic agents in preclinical models [97,98].…”