Sm. Moghimi et B. Bonnemain, Subcutaneous and intravenous delivery of diagnostic agents to the lymphatic system: applications in lymphoscintigraphy and indirect lymphography, ADV DRUG DE, 37(1-3), 1999, pp. 295-312
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.