Multimodal assessment of early tumor response to chemotherapy: comparison between diffusion-weighted MRI, 1H-MR spectroscopy of choline and USPIO particles targeted at cell death

• Published in: NMR in biomedicine 2012-04, Vol.25 (4), p.514-522
• Main Authors: Radermacher, K. A., Magat, J., Bouzin, C., Laurent, S., Dresselaers, T., Himmelreich, U., Boutry, S., Mahieu, I., Vander Elst, L., Feron, O., Muller, R. N, Jordan, B. F., Gallez, B.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Biomarkers, Tumor - analysis; Cell Line, Tumor; choline; Choline - analysis; Dextrans; Diffusion Magnetic Resonance Imaging - methods; diffusion-weighted imaging; EPR; Liver Neoplasms - diagnosis; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Magnetic Resonance Spectroscopy - methods; Magnetite Nanoparticles; Mice; MR spectroscopy; MRI; Protons; Reproducibility of Results; Sensitivity and Specificity; targeted contrast agent; Treatment Outcome; Tumor response
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.1765

The aim of this study was to determine the value of different magnetic resonance (MR) protocols to assess early tumor response to chemotherapy. We used a murine tumor model (TLT) presenting different degrees of response to three different cytotoxic agents. As shown in survival curves, cyclophosphamide (CP) was the most efficient drug followed by 5‐fluorouracil (5‐FU), whereas the etoposide treatment had little impact on TLT tumors. Three different MR protocols were used at 9.4 Tesla 24 h post‐treatment: diffusion‐weighted (DW)‐MRI, choline measurement by 1H MRS, and contrast‐enhanced MRI using ultrasmall iron oxide nanoparticles (USPIO) targeted at phosphatidylserine. Accumulation of contrast agent in apoptotic tumors was monitored by T2‐weighted images and quantified by EPR spectroscopy. Necrosis and apoptosis were assessed by histology. Large variations were observed in the measurement of choline peak areas and could not be directly correlated to tumor response. Although the targeted USPIO particles were able to significantly differentiate between the efficiency of each cytotoxic agent and best correlated with survival endpoint, they present the main disadvantage of non‐specific tumor accumulation, which could be problematic when transferring the method to the clinic. DW‐MRI presents a better compromise by combining longitudinal studies with a high dynamic range; however, DW‐MRI was unable to show any significant effect for 5‐FU. This study illustrates the need for multimodal imaging in assessing tumor response to treatment to compensate for individual limitations. Copyright © 2011 John Wiley & Sons, Ltd. Non‐invasive assessment of early tumor response to chemotherapy by different magnetic resonance protocols: diffusion‐weighted MRI; choline measurement by 1H MRS and contrast enhanced MRI using ultrasmall iron oxide nanoparticles targeted at phosphatidylserine. This work illustrates the need for multimodal imaging in assessing tumor response to treatment to compensate for individual limitations. The figure shows ADCw maps of tumor‐bearing mice before and 24 h after injection of different cytotoxic treatments.