Lymphoscintigraphy: Radiopharmaceutical selection and methods

Abstract

Lymphoscintigraphy offers the clinician unique access to lymph nodes and lymphatics which otherwise may be unavailable for evaluation by noninvasive means. By deposition of a radioactive lymphoscintigraphic agent in a tissue whose lymphatic drainage requires definition or whose lymph nodes require evaluation, both dynamic and static functional information concerning the patency and anatomy of lymph vessels and nodes may be obtained. There is currently a broad range of radiopharmaceuticals available for lymphoscintigraphy. They fall into 3 ma.jor categories: radiocolloids, radiolabeled macromolecules, and within the macromolecule category, monoclonal antibodies for tumor detection. Uptake into lymphatic vessels is presumed to occur by a common mechanism. Radiolabeled colloids or macromolecules may either enter lymph channels through lymphatic capillaries passively or, in the case of colloids, be phagocytosed by macrophages and transported within lymphatic channels. Depending upon the size of the macromolecule, some blood capillary uptake is believed to occur from the injection site causing higher blood background levels. However, the absence of a basement membrane in lymphatic vessel endothelium permits entrance of molecules into the lymphatics which are excluded by blood capillary endothelium (Wahl et al., 1987). Colloidal particles are trapped in macrophages within the lymph nodes (Peyton, 1981). The accumulation of radiocolloid or radiolabeled macromolecules will depend upon the presence of a functionally intact node. Replacement of nodes by tumor or recent surgery in the area drained by the lymph node group may affect the ability of a lymph node to accumulate the particle or molecule. The nonspecific macromolecules (99”Tclabeled noncolloidal human serum albumin and 99mTc-labeled dextran) generally demonstrate a shorter residence time in the nodes than colloids. Some radiolabeled particles or molecules will pass beyond the draining nodes, eventually draining into the venous system, and, finally, becoming trapped in the reticuloendothelial system. From the lymphatics, access by the macromolecules is eventually gained to the venous system where blood pool activity and renal activity due to clearance through the kidneys may be seen. The selection of the lymphoscintigraphic agent depends upon the information required from the study. Historically, radiocolloids were the first lymphoscintigraphic agents used. Sage et al. (1964) and Fee et al. (1978) used [198Au]gold colloid to study lymphedema and melanoma, respectively. The radioactive gold colloid provided an ideally sized particle (2-10 nm) which permitted relatively rapid clearance from injection sites into lymphatic channels. However, the long physical half-life (2.7 d) and fl radiation emission severely limited the amount of radioactivity which could be administered. Even with the usually administered dose of 15OpCi (5.6 MBq) radiation necrosis at the injection site was reported (Osborne et al., 1983). Ultimately, gold colloid was abandoned because of the unacceptable dosimetry. 99”Tc-sulfur colloid offered an alternative. Although the physical half-life emission characteristics were more suited to human use and y camera imaging, the larger particle size (100 nm to 2 pm) meant that significant numbers of the colloid particles either failed to enter the lymphatic system or entered very slowly. Clearance from the injection site of only 30% over several hours is typical. Thus, in theory, because change in the distribution of this radiocolloid occurs more slowly, dynamic imaging should be less satisfactory with this preparation. Nonetheless, primary lymphedema as well as dermal lymphatic drainage have been explored using this radiocolloid. One alternative has been to filter 99mTc-sulfur colloid through a millipore filter (Sacks et al., 1983). This provides a smaller particle ( -=I 220 nm). %Tc--rhenium colloid provides an average sized particle of 40 nm. Although not available in the U.S., it has been used for lymphoscintigraphy in Europe. In the mid-1960s, Garzon (1965) developed a method to make *Tc-antimony trisulfide colloid. The average particle size of 12 nm is more suited to