Hepatobiliary Imaging

Reinhard Kloiber and Gary R. May Introduction

Historically, liver imaging using radionuclides focused on the detection of liver masses. More recently, anatomic imaging modalities including ultrasound, CT and MRI have replaced colloid imaging because of their greater sensitivity and ability to distinguish cystic from solid lesions. Solid masses may nevertheless have a nonspecific appearance on anatomic imaging requiring the use of radiopharmaceuticals that identify certain cell lines, metabolic properties or surface characteristics of specific lesions. The modern technetium-99m labeled hepatobiliary agents retain a pivotal role in studying biliary flow and dynamics.

Radiopharmaceuticals

IDA Analogues

Analogues of technetium-99m labeled iminodiacetic acid (99mTc-IDA) first became available for clinical use in the 1970s and remain the most widely used radiopharmaceuticals for hepatobiliary imaging (Fig. 1). After intravenous injection, these organic anions are taken up by hepatocytes in a manner similar to bilirubin. They are secreted into bile without conjugation. 99mTc-IDA uniformly mixes with bile, thereby becoming a marker of bile flow to the gallbladder and bowel. No significant intestinal reabsorption or enterohepatic cycling occurs. Ideal agents exhibit high extraction efficiency by liver (even in the presence of liver dysfunction), rapid transit, and high concentration in bile. Commercially available 99mTc-disofenin (Hepatolite®) and 99mTc-mebrofenin (Choletec®) meet these criteria.

Colloids

99mTc-sulfur colloid and a variety of other colloids are phagocytosed from the blood stream by Kupffer cells in the liver and other reticuloendothelial cells. Under normal circumstances, 85% of the dose accumulates in liver, 10% in the spleen and the remainder in bone marrow (Fig. 2). Metastases, cysts and abscesses all displace normal Kupffer cells and appear as "cold" defects. Some benign focal liver lesions contain Kupffer cells and the benign nature of the mass can be confirmed by showing colloid uptake within it.

Red Blood Cells

Red blood cells can be labelled with technetium-99m (99mTc-RBC) and are used to identify cavernous hemangiomas within the liver. These consist of large blood filled spaces. Blood flow is generally low in relation to the volume of blood present and filling after intravenous injection of a substance may require a significant period of time. Radiographic contrast material leaks rapidly from the intravascular space

Nuclear Medicine, edited by William D. Leslie and I. David Greenberg. ©2003 Landes Bioscience.

Figure 1. Structure of iminodiacetic acid. The groups on the benzene ring labelled R can be hydrogen or short organic chains. They determine the specific attributes of the analogue such as avidity of uptake by the liver and rates of excretion.

into the extracellular fluid space. Late enhancement of a mass on CT therefore does not prove that the lesion is filled with blood but can also be seen in malignant masses with an expanded extracellular fluid space. 99mTc-RBCs remain confined to the circulation and even hemangiomas that require hours to equilibrate can be correctly diagnosed. (For more on the technique of labelling RBCs, refer to Chapter 4.)

Other tracers

Antibodies

Antibodies directed at characteristic surface antigens selectively expressed by specific neoplasms, such as prostate specific antigen (PSA) or carcinoembryonic antigen (CEA), appear in theory to be the ideal agents. Unfortunately, all antibodies or fragments are metabolized in liver yielding a high background. Mapping of normal tissue with 99mTc-sulfur colloid and subtraction from the antibody images to highlight areas of abnormal binding can improve detectability. Antibody imaging of liver lesions holds theoretical promise but, after years of investigation, is still of limited clinical utility.

Receptor-Specific Agents

The indium-111 labelled pentapeptide analogue of somatostatin (mIn-pentetreotide or octreoscan® binds to receptor-positive carcinoids and a variety of pancreatic islet cell and neuroendocrine tumours. Lesion to liver ratios are often sufficiently high to confirm the nature of metastases (Fig. 3). Extrahepatic sites are demonstrated with even greater sensitivity. The technique is complementary to CT.

Gallium Citrate

Certain neoplasms, including lymphomas, carcinoma of the lung, sarcomas and hepatomas, may exhibit avid uptake of gallium-67 citrate (67Ga). Gallium acts as an iron analogue. It binds to transferrin after intravenous injection and is stored in liver and bone marrow. Small quantities are excreted in bile. Normal liver therefore contains moderately high background activity. Many adenocarcinomas originating in the gastrointestinal and genitourinary tracts show only low grade uptake and metastases appear as photopenic defects relative to normal liver. Imaging characteristics of 67Ga are poor compared with 99mTc and the masses must be substantial in size to be

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