MR in oncology drug development

Abstract

This article reviews the use of MR in preclinical and clinical experiments to aid drug development. In particular it concentrates on the use of MR to study tumor microvasculature following treatment with anti-vascular agents and the use of MRS to study tumor metabolism following treatment with a variety of anti-cancer agents. The advantages and disadvantages of a variety of techniques including contrast-and noncontrast-enhanced methods are discussed and the data from clinical trials using these techniques are reviewed. Despite the consensus documents produced to date for both dynamic contrastenhanced MRI and MRS, most of the trials reported used alternative methods, and different nomenclature for the MR parameters used. This continues to inhibit the comparison between novel therapeutics and between different trials with the same compound. Comprehensive data from multicenter trials on the reproducibility of techniques is still lacking in the literature and the implications of the available data on clinical trial design is also discussed.

The magnetic resonance shutter speed discriminates vascular properties of malignant and benign breast tumors in vivo

“…This far outweighs the tiny incidence [0.00045% of the Ͼ30 million patients who have received a particular, suspect CR (34)] of serious reaction to CR administration, and which correlates with preexisting kidney compromise. We expect the SSM to also significantly quantify the proven DCE-MRI ability to detect very early responses to anticancer therapeutic interventions with approved drugs (16) and in drug discovery (35,36). And the SSM has much more to teach us.…”

Fundamentals of tracer kinetics for dynamic contrast‐enhanced MRI

“…In DCE MRI, a commonly used metric that relates to the central volume principle is the initial area under curve, IAUC (17)(18)(19), which computes the area under C tiss (t) up to a stipulated time t max that encompasses a major portion of C tiss (t) (typically, t max % 60-100 sec after tracer injection). When normalized by the corresponding area under…”

“…In DCE MRI of tumors, IAUC norm would be indicative of the combined volumes of m p and m e , and several studies have shown its usefulness as a potential biomarker in antiangiogenic drug trials (17)(18)(19). Other modifications to the IAUC metric have also been proposed, which can be sensitive to different tissue parameters (29).…”

“…As the presence of gadolinium leads to shortening of both T 1 and T 2 relaxation times in the tissue, resulting in signal enhancement in T 1 -weighted images and signal loss in T 2 -(and T2 Ã -) weighted images, dynamic MRI can be performed using either T 1 -weighted imaging sequences (12)(13)(14)(15)(16)(17)(18)(19) or T 2 -(T2 Ã -) weighted sequences (20)(21)(22)(23)(24). While the former is commonly known as DCE MRI, the latter is called dynamic susceptibility contrast-enhanced (DSC) MRI.…”

“…However, in most tissues (except the brain, testes, and retina), and especially in tumors, low-molecular weight gadolinium contrast agents readily pass into the interstitial space during first pass and T 1 -weighted DCE MRI is sensitive to the leakage of contrast agents in the interstitial space, as well as those remaining in the vascular space. Recent few years have seen a rapid increase in the use of T 1 -weighted DCE MRI for assessment of tumor angiogenesis in clinical trials (17)(18)(19).…”