An ultrasmall superparamagnetic iron oxide (USPIO) preparation was evaluated as a potential intravenous contrast agent for lymph nodes. Relaxation time measurements and magnetic resonance (MR) imaging were performed in rats with normal lymph nodes and in rats with lymph node metastases. In normal animals, lymph node relaxation times decreased maximally within 24-48 hours after intravenous administration of USPIO. Twenty-four hours after administration, the T2 of normal lymph nodes had decreased from 74 msec +/- 2.2 to 30 msec +/- 0.7 (USPIO, 40 mumol of iron per kilogram) or 15 msec +/- 0.0 (200 mumol Fe/kg), whereas the T2 of metastatic nodes did not change. MR imaging of the animal model of nodal metastases confirmed the hypothesis that intravenously administered USPIO decreases signal intensity of normal but not metastatic nodes. A single intravenous administration of USPIO may allow detection of nodal metastases on the basis of signal intensity characteristics rather than the currently used, insensitive size characteristics.

The authors developed and evaluated a polymer as a contrast agent for magnetic resonance (MR) angiography. The agent consists of a monomethoxy ether of poly(ethylene glycol) covalently attached to poly(L-lysine) (PL), with PL serving as the carrier of gadolinium diethylenetriaminepentaacetic acid (DTPA). Immunogenicity and toxicity studies were performed in mice, and biokinetic and metabolic studies were performed in rats. Dose response studies were performed with a three-dimensional time-of-flight sequence in eight rats. No permanent immune response was elicited against Gd-DTPA or the carrier molecule, and accumulation in organs of the reiculoendothelial system was minimal. The blood half-life of the agent was 14 hours. A dose of 20 mumol of gadolinium per kilogram of body weight was sufficient to increase the vessel-muscle ratio by four- to fivefold. Contrast was substantially improved and remained unchanged 2 hours after contrast medium administration, and good visualization of four orders of vasculature was allowed.

Echo-planar imaging appears promising for quantification of breast lesion enhancement. Microvessel data indicate that tumor angiogenesis affects enhancement.

The potential of superparamagnetic ferrite particles as a contrast agent for magnetic resonance (MR) imaging was studied by in vitro MR spectroscopy and in vivo MR imaging in laboratory animals. After aqueous preparations of ferrite particles were administered intravenously, MR spectroscopy showed greatly decreased T2 relaxation times of liver and spleen, with only minimally altered T1, and no changes in lung, kidney, or muscle. Effects occurred within 30 minutes of injection and persisted for more than 6 months. MR imaging with pulse sequences that provide T2-dependent contrast demonstrated that ferrite produced profound signal loss from liver, spleen, and bone marrow. Sequestration of ferrite particles in hepatic reticuloendothelial cells was confirmed by means of light and electron microscopy. Because ferrite has a potent effect on MR signal and exhibits tissue-specific localization, it warrants further study as a contrast agent for MR imaging of the reticuloendothelial system (i.e., liver, spleen, and bone marrow).

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