MRI offers in-depth, biodynamic view of cellular therapy

Nov 1, 2005

In ongoing clinical trials of dendritic cell vaccines, only a limited proportion of patients have responded successfully. This may be because of inadequate delivery, as dendritic cells must migrate throughout the vascular and lymphatic systems to be effective. Dutch and U.S. researchers have suggested that MRI can be very useful for tracking these cells.

For the time being, only scintigraphy is approved by the Food and Drug Administration for monitoring dendritic cell movement, explained I. Jolanda de Vries and colleagues from Radboud University Nijmegen Medical Centre in Nijmegen, Netherlands, and the Johns Hopkins University School of Medicine in Baltimore. Unfortunately, scintigraphy has its shortcomings, such as a lack of anatomic detail and poor spatial resolution.

"In contrast, MRI is well suited to obtain three-dimensional, whole-body, high-resolution images and is widely used in clinical practice," the group wrote. "We found that cells could be labeled with [(ultrasmall) paramagnetic iron oxide particles or SPIO] with high efficiency without affecting their function" (Nature Biotechnology, October 30, 2005).

In their experimental study on eight patients with stage III melanoma, the researchers obtained MR images before surgery, generated high-resolution 7-tesla images of resected lymph nodes, and correlated results with scintigraphy and immunohistopathology.

Under ultrasound guidance, the patients received intranodal injections of indium-111 and SPIO-labeled dendritic cells before radical dissection of regional lymph nodes. Images were obtained on a 3-tesla MR system (Magnetom Trio, Siemens Medical Solutions, Erlangen, Germany), and the protocol included T2^*-weighting with an average echo time of 15 msec, as well as turbo spin-echo imaging using a short echo time of 18 msec.

Ex vivo MRI of the lymph nodes was performed using a 7-tesla MR spectrometer (Surrey Medical Imaging Systems, Guildford, U.K.). In vivo and ex vivo planar scintigraphic images were acquired with a gamma camera (ECAM, Siemens Medical Solutions). Finally, sections of the radioactive resected lymph nodes were stained with Prussian blue to detect SPIO-labeled cells.

According to the results, "a comparison of gradient-echo images before and after cell injection showed that the injected SPIO-labeled dendritic cells result in a significant decrease in signal intensity at the injection site." Additionally, in the spin-echo images, lymph nodes appeared as dark-gray structures versus white on gradient-echo images.

In one patient, scintigraphy identified four positive lymph nodes, whereas MR picked up one additional hot spot. The latter turned out to be two separate nodes with the second one lying close to the injection site, they authors wrote.

"In contrast to MRI ... scintigraphy cannot distinguish between correct and incorrect intranodal injections, leading to erroneous classification of injection sites as lymph nodes," they added.

"We demonstrated that MRI is at least as sensitive as scintigraphic imaging for detecting dendritic cell migration in vivo," the authors stated, reiterating the modality's strengths of anatomical background contrast, precise anatomical localization of SPIO-labeled cells at the injection site as well as after migration, high spatial resolution for finding separate lymph nodes, and a lack of saturation of images. They also pointed out that they used a routine MRI protocol that could be reproduced on any system.

In what the authors called an "interesting" secondary finding, they discovered that in only half of the cases were the dendritic cells correctly injected despite sonographic guidance by an experienced radiologist. This bolsters the case of using MRI to monitor cell treatment, they wrote.

By Shalmali Pal
AuntMinnie.com staff writer
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