Subcutaneous and intravenous delivery of diagnostic agents to the lymphatic system: applications in lymphoscintigraphy and indirect lymphography

Lymph node status is important in the staging of many malignancies. Althoug h tissue characterization by histologic analysis of biopsy samples may impr ove staging, noninvasive staging is more acceptable to both patients and cl inicians. Several imaging techniques may serve this goal. Modern noninvasiv e techniques such as computed tomography and magnetic resonance detect lymp h node abnormality by nodal enlargement, but that does not always imply mal ignant involvement. On the other hand, many nodes are infiltrated or replac ed by tumour without change in size. This becomes a serious diagnostic defe ct by these modalities. Consequently, attention has been focused to develop contrast agents and radiolabelled complexes for better cancer detection as well as characterization of individual tumours in lymph nodes. For deliver y of such materials to regional lymph nodes one can take advantage from the distinct physiological function of the lymphatic capillaries. The thin-wal led and fenestrated lymphatic microvessel is easily penetrated by particula te and macromolecular agents after injection into the extracellular space. Once inside the vessel, materials that are transported with the lymph eithe r specifically target certain nodal elements (e.g. neoplastic cells) or bec ome cleared by macrophages located in the lymph nodes. Indeed, interstitial delivery of diagnostic agents have been of benefit in determining regional spread of cancer and assessing lymphatic function either by lymphoscintigr aphy or indirect lymphography. On the other hand, development of contrast m aterials that can reach lymph nodes after a single intravenous injection is highly desirable because of the large number of lymph nodes in the body an d access being difficult to most of them. Today, a number of contrast agent s exist that can reach a vast array of lymph nodes in the body, particularl y those that are not readily accessible for histologic evaluation, after a single intravascular injection to help distinguish between normal and tumou r-bearing nodes or reactive and metastatic nodes with magnetic resonance. I n this article we critically examine advantages and limitations of both sub cutaneous and intravenous routes of injection for the delivery of diagnosti c agents to the lymphatic system. (C) 1999 Elsevier Science BN. All rights reserved.