Exploiting Lymphocyte Traffic to Deliver Radioactivity or Ricin to Lymphatic Tissues

• DOI: 10.1007/978-1-4613-2463-8_83
• Publication Date: 2011-10-01T23:06:36Z
• Authors: W. L. Ford; A. J. S. Davies; M. Birch; J. A. Forrester; D. McIntosh; H. Sharma; S. Sparshott; C. Wood
• Keywords: Radioisotopes; Time Factors; Cell Movement; Lymphoid Tissue; Macrophages; Cell Adhesion; Animals; Lymph Nodes; Lymphocytes; Ricin; Indium; Spleen; Rats

After injection into the bloodstream lymphocytes localize in the traffic areas of the spleen and lymph nodes where they reach a concentration approximately 500 times greater than the concentration averaged over the whole body and about 25,000 times the concentration in most non-lymphatic tissues such as muscle. This selective localization develops rapidly so that under physiological conditions over 90% of lymphocytes leave the blood stream to enter lymphatic tissues within one hour1Can this remarkable process be exploited in order to target drugs to certain sites? Two current projects in the Manchester Immunology department have the common objective of examining the practicability of using lymphocytes in order to carry, deposit and concentrate materials in lymphatic tissues. For this principle to be effective three conditions require to be fulfilled - 1) the material must be suitable for “loading” into lymphocytes in vitro; 2) loaded lymphocytes must remain capable of their normal migratory behaviour for at least 30–60 min so that they enter the lymphatic tissues after intravenous injection; 3) when the loaded cells have reached the organ they must release the material in such a form that it affects neighbouring cells. It may be taken up by macrophages and so retained in the tissue.