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    Novel MRI technique detects metastases in PCa patients

    Accuracy, less-invasive nature appear to allow more efficient staging, better outcomes

    A benign adenopathy is difficult to see with conventional MRI (photo A - top). After injection of ferumoxtran-10, the adenopathy is clearly visible 24 to 36 hours later (photo B - second). The difference between benign nodes and malignant nodes is also clearly visible with the MRI agent (third and bottom), allowing for better staging of the nodes. (Photos courtesy of Mukesh Harisinghani, MD)
    Seattle-A new study by American and Dutch researchers suggests that high-resolution magnetic resonance imaging studies using an iron-oxide-containing contrast agent offer the ability to produce a very accurate localization of tumor metastases in prostate cancer patients.

    "These new imaging techniques allow us to clearly distinguish between benign and malignant nodes and to construct three-dimensional maps to guide surgical planning," said lead author Mukesh Harisinghani, MD, assistant professor of radiology at Massachusetts General Hospital and Harvard Medical School, Boston. "This approach also has the potential to be applied to a wide variety of malignancies.

    "And eventually, we could go beyond staging the disease to offering treatments using lymphotropic agents that could attack the metastases without the systemic effects of other chemotherapy drugs."

    Increased sensitivity of MRI Researchers at Massachusetts General Hospital and the University Medical Center in Nijmegen, the Netherlands, conducted a study with 80 patients to investigate whether highly lymphotropic superparamagnetic nanoparticles could be used with MRI to reveal small nodal metastases.

    The researchers used an iron oxide imaging agent known as ferumoxtran-10 (Combidex, Advanced Magnetics, Inc., Cambridge, MA), which currently is being evaluated for approval by the FDA. The agent was reconstituted in normal saline and injected at a dose of 2.6 mg of iron/kg of body weight over a period of about 30 minutes.

    Each institution enrolled 40 patients with presurgical clinical stage T1, T2, or T3 prostate cancer who underwent surgical lymph node resection or biopsy. All patients were examined by MRI before and 24 hours after the administration of ferumoxtran-10. A total of 334 lymph nodes were imaged in the 80 patients. The imaging results were then correlated to the various histopathological findings.

    The researchers found that, on a patient-by-patient basis, the addition of ferumoxtran-10 increased the sensitivity of MRI from 45.5% to 100%, with a specificity of 95.7%.

    The MR studies indicated that, of the 334 lymph nodes, 271 (81.1%) of the imaged nodes were benign. Detectable metastases were found in 63 nodes (18.9%) from 33 patients (41%). All of these diagnoses were confirmed by pathological examination of the removed nodes.

    Of the 63 malignant nodes, 17 measured less than 5 mm, 28 were 5 to 10 mm, and 18 exceeded 10 mm. The researchers concluded that, overall, 71.4% of the malignant nodes would not have fulfilled the traditional imaging criteria for malignancy.

    "The high accuracy and less invasive nature of this method will allow us to stage our prostate cancer patients more efficiently," said co-author Shahin Tabatabaei, MD, a urologist at Massachusetts General Hospital. "This technique may revolutionize the diagnosis and treatment of prostate cancer and probably other genitourinary malignancies."

    Evolution of diagnosis, Tx Dr. Tabatabaei said his team has planned large-scale, controlled follow-up studies.

    "This is important to urologists," Dr. Tabatabaei told Urology Times. "It will significantly shift the paradigm for diagnosis (lymph node status) and treatment of genitourinary cancers."

    Dr. Harisinghani said the research marks a tremendous leap from what has been used previously for nodal staging. The imaging technique could have wide applications.

    "In bladder and testicular cancer, knowing the nodal status before surgery is very important. So for urologists, this new technique would provide better staging and hopefully better outcomes," he said.

    Hevig Hricak, MD, professor and chairman of radiology at Memorial Sloan-Kettering Cancer Center, New York, said the new contrast agent provides a "roadmap" that will greatly help urologists. However, she said more studies would be required to determine exactly how and where it should be used, and the current technology does have some drawbacks.

    "You have to inject it one day and image another day. So, it is not that easy on the patient. They have to come to the hospital one day and then come back the next," Dr. Hricak said.

    Richard D. Williams, MD, professor and chairman of the department of urology at the University of Iowa, Iowa City, said he agreed with Dr. Hricak, adding that this imaging technique offers a great deal of promise and may greatly improve prostate cancer management. However, more research is needed.

    "What we have now is imprecise and not good enough for pre-management decisions on patients, unless they have extensive disease," Dr. Williams told Urology Times. "It is an advance. It sounds like it has great promise, and it deserves a bigger study at more institutions to corroborate the data."