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Preclinical Studies and Early Drug Development: In Vitro and In Vivo Assays and Models

Metabolic characterization by in vivo proton magnetic resonance spectroscopy (PMRS) - predicts the post treatment status of the soft tissue sarcomas?

Himalayan Institute of Medical Sciences, Dehardun, Uttaranchal,India, India and All India Institute of Medical Sciences,, New Delhi, India, India

Abstract

B5

Objective: It is always very difficult to assign a grade which is the most important prognostic factor in soft tissue sarcoma. It is not also easy to measure the therapeutic efficacy which is also because of its heterogenity. The aim of this study is to evaluate the correlation of in vivo proton magnetic resonance spectroscopic findings with histopathological features at different states of soft tissue sarcomas in (pretreatment and post treatment).Methods: PMRS Study was performed at 1.5Tesla MRI machine with a surface coil appropriate for the location of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterized the heterogeneity of the tumor in 15 cases by using point - resolved spectroscopic sequence (PRESS) with echo time TR=2000 / TE = 30, 135 & 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered as significant. MRS results and histopathology findings were correlated and P < 0.001, considered being significantResults: Choline peak was found in 17 out of 17 patients with malignant soft tissue tumors where as three patient with benign and five treated malignant soft tissue tumour patients with no residual disease did not show any choline. Out of nine patients having suspected residual or recurrent diseases four patients had significant choline peak in this study. In vivo Spectroscopy here shows sensitivity, specificity, (p < 0.001), positive predictive value, negative predictive value and accuracy of 100% each.Conclusion: In vivo PMRS study can differentiate the malignant from benign soft tissue tumor, tumour heterogeneity (especially CSI) and tumour activity in recurrent and / or residual soft tissue sarcoma. This may be a good adjunct to clinical and pathological diagnosis to assess post treatment status of the disease and further major study is required to validate the method for routine clinical use.