Magnetic Targeted Carriers Offer Site-Specific Drug Delivery

SAN DIEGO—External magnets are being used to guide a novel, intra-arterially administered chemotherapy delivery vehicle directly to the tumor site (see illustration ). Scott C. Goodwin, MD, chief of vascular and interventional radiology, UCLA Medical Center, reported results of an ongoing phase I/II study of this new regional therapy technique at the annual scientific meeting of the Society of Cardiovascular & Interventional Radiology.

The product, MTC-DOX, currently being tested in primary liver cancer patients, is under development by San Diego-based FeRx Incorporated. It consists of doxorubicin adsorbed to the company’s proprietary Magnetic Targeted Carriers (MTCs).

MTCs are microparticles ranging from 1 to 2 microns in size, composed of elemental iron and activated carbon, which serve as delivery vehicles for the site-specific targeting, retention, and sustained release of the pharmaceutical. The iron component provides the needed magnetic character, while the carbon component provides carrying capacity for the drug. The MTCs are manufactured at the company’s facility in Arvada, Colorado.

“With MTCs, we hope to get a significant amount of toxic cancer-killing drugs to remain in the tumor, rather than spreading throughout the body, thereby reducing side effects such as nausea and hair loss,” Dr. Goodwin said. “Our early results make us hopeful that site-specific drug delivery with MTCs will improve response rates of anticancer drugs, while at the same time reducing the complications of chemotherapy.”

Dr. Goodwin presented data on 14 patients with advanced hepatocellular carcinoma who received a single dose of MTC-DOX via intra-arterial infusion. Doses ranged from 3 mg doxorubicin/37.5 mg MTCs to 18 mg doxorubicin/225 mg MTCs.

The drug solution is mixed with the vialed MTCs just prior to administration. The agent is then given via a catheter placed in a subsegmental branch of a hepatic artery feeding the tumor to be treated.

In this study, delivery was targeted to a single lesion in a specific hepatic segment, using a small, externally positioned magnet (5 kilogauss) to creat a localized magnetic field within the body over the tumor site. The physical force created by the magnetic field induces transport (extravasation) of the MTCs through the vascular wall (see Figure 1).

The external magnet remains in place for about 15 minutes after dosing. Upon removal of the magnet, the MTCs do not recirculate but are retained in the tissue where the drug then desorbs from the MTCs, leading to sustained release of the particles at the desired site.

Angiography was performed before and after dosing, and patients underwent baseline and 28-day follow-up CT and magnetic resonance (MR) images to document tumor size and number of lesions as well as MTC particle distribution. In patients with multiple lesions, the non-targeted lesions were used as controls.

Dr. Goodwin reported that MR im-ages have shown deposition of the particles solely in the selected site, as seen in Figures 2 and 3. The MTC-DOX is seen as darkened areas within the liver. This is due to the iron component of MTC, which acts as a negative contrast agent in MR imaging.

“After 28 days, MRI results show that the particles remain in the targeted site with no redistribution,” Dr. Goodwin said. Angiography has shown no significant arterial embolization (see the illustration ), and no study-related deaths have occurred.

This preliminary report shows that of the first 14 patients, one patient had a partial response (greater than 50% tumor reduction), and two patients had a minor response (25% to 50% tumor reduction). Five patients had stable disease, and six had disease progression.

FeRx plans to initiate phase II trials of MTC-DOX later this year to further assess dosing, safety, and efficacy in patients with primary liver cancer, and also plans to expand the development program to other solid tumors.