MRI & MRS assessment of the role of the tumour microenvironment in response to therapy

Abstract

MRI and MRS techniques are being applied to the characterisation of various aspects of the tumour microenvironment and to the assessment of tumour response to therapy. For example, kinetic parameters describing tumour blood vessel flow and permeability can be derived from dynamic contrast-enhanced MRI data and have been correlated with a positive tumour response to antivascular therapies. The ongoing development and validation of noninvasive, high-resolution anatomical/molecular MR techniques will equip us with the means to detect specific tumour biomarkers early on, and then to monitor the efficacy of cancer treatments efficiently and reliably, all within a clinically relevant time frame. Reliable tumour microenvironment imaging biomarkers will provide obvious advantages by enabling tumour-specific treatment tailoring and potentially improving patient outcome. However, for routine clinical application across many disease types, such imaging biomarkers must be quantitative, robust, reproducible, sufficiently sensitive and cost-effective. These characteristics are all difficult to achieve in practice, but image biomarker development and validation have been greatly facilitated by an increasing number of pertinent preclinical in vivo cancer models. Emphasis must now be placed on discovering whether the preclinical results translate into an improvement in patient care and, therefore, overall survival.

Exploiting tumor metabolism for non-invasive imaging of the therapeutic activity of molecularly targeted anticancer agents

“…82 These various measurements can be performed using the same scanners and during the same imaging examination, thus providing valuable co-registered spatial and temporal information on the additional microenvironmental aspects of therapeutic activity exerted by the targeted agents and helping to understand how these might be related to the metabolic changes induced in tumors.…”

Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

“…First, homeostatic factors that compose up to 90% of the tumor mass in some tumors have great essentiality to influence the level of malignant aggression and treatment outcomes 6. Homeostatic factors render tumor microenvironment also as a therapeutic target besides cancer cells 7. Secondly, necrotic tissues, which comprise 30-80% of a solid tumor and locate always close to the viable cancer cells, can function as a universal anchor for targeting malignancies 8-11.…”

Mapping of amide, amine, and aliphatic peaks in the CEST spectra of murine xenografts at 7 T

“…Methods such as DCE‐MRI and quantitative T 1 /T 2 are well‐established examples, and more recently chemical exchange saturation transfer (CEST) MRI has been applied in the characterization of cancer . It has been hypothesized that changes in CEST contrast reflect changes in the tumor microenvironment . More specifically, altered CEST contrast can represent changes in the local chemical environment of specific metabolites, and has been linked to altered cellular metabolism pathways and apoptosis .…”