The Scope E-Newsletter September 2009 Solomon, Wall Lead Innovative Clinical Trial to Image Amyloidosis

Patients with primary (AL) amyloidosis throughout North America are coming to the UT Graduate School of Medicine to participate in an on-going clinical trial under the direction of Alan Solomon, MD, Program Director, Human Immunology and Cancer Program, and Jonathan Wall, PhD, Director, Preclinical and Diagnostic Molecular Imaging Laboratory. The U.S. Food and Drug Administration-sponsored study, "Radioimmunoimaging of AL Amyloidosis," intends to determine if a radiolabeled anti-amyloid monoclonal antibody can be used to image by PET/CT amyloid deposits in such patients with primary (AL) amyloidosis.

Drs. Solomon and Wall and their radiochemist colleague, Stephen Kennel, PhD, have shown that when the antibody designated 11-1F4 was attached to a positron-emitting isotope, iodine 124, and given to mice bearing human amyloid tumors it bound to this material as visualized by PET/CT scans. This discovery led to an application to the FDA for permission to test in up to 30 patients whether the radiolabeled antibody would visualize amyloid deposits in the heart, liver, kidney or other affected organs of patients with AL amyloidosis. In 2008, the FDA gave their approval to proceed with the study, which is supported by a two-year grant from their Office of Orphan Products Development Research Grants Program and provides $200,000 per year to cover costs of the study, including the isotope and participant travel. If successful, this will be the first FDA-approved means to image this type of amyloid in the U.S.

To date, with the assistance of highly trained, dedicated nursing and medical personnel in the University of Tennessee Medical Center's Nuclear Medicine Department, who are responsible for administering the product and performing the PET/CT scans using Siemens's latest and highly sensitive instrument, 15 patients have been studied, with dramatic results in at least eight. Dr. Solomon is still recruiting patients who have been diagnosed with AL amyloidosis for the imaging study and he may be contacted directly about participation.

Additionally, the UT investigators also showed that under experimental conditions, larger doses of the 11-1F4 antibody could eliminate the amyloid tumors in the animals and thus this agent has potential as a novel means of treating patients with AL amyloidosis. This finding and the results from the radioimmunoimaging trial recently led the National Cancer Institute's Drug Development Group to allocate $3 million to the production and testing of the antibody for an eventual clinical trial, estimated to begin in 18 months.

"This research is being done solely here, in this one place, UT Graduate School of Medicine at University of Tennessee Medical Center, and it's really a remarkable accomplishment," said Dr. Solomon.