Optimization of monoclonal antibody delivery via the lymphatics: the dose dependence

Journal Article · Tue Apr 01 04:00:00 EST 1986 · Cancer Res.; (United States)

OSTI ID:5619937

Steller, M A; Parker, R J; Covell, D G; Holton, O.D. 3d.; Keenan, A M; Sieber, S M; Weinstein, J N

After interstitial injection in mice, antibody molecules enter local lymphatic vessels, flow with the lymph to regional lymph nodes, and bind to target antigens there. Compared with i.v. administration, delivery via the lymphatics provides a more efficient means for localizing antibody in lymph nodes. An IgG2a (36-7-5) directed against the murine class I major histocompatibility antigen H-2Kk has proved useful for studying the pharmacology of lymphatic delivery. At very low doses, most of the antibody remains at the injection site in Kk-positive animals. As the dose is progressively increased, most effective labeling occurs first in nodes proximal to the injection site and then in the next group of nodes along the lymphatic chain. At higher doses, antibody overflows the lymphatic system and enters the blood-stream via the thoracic duct and other lymphatic-venous connections. Once in the blood, antibody is rapidly cleared, apparently by binding to Kk-bearing cells. These findings indicate that the single-pass distribution of monoclonal antibodies in the lymphatics can be strongly dose dependent, a principle which may be of clinical significance in the improvement of immunolymphoscintigraphic imaging, especially with antibodies directed against normal and malignant lymphoid cells. Monoclonal antibodies directed against normal cell types in the lymph node may be useful for assessing the integrity of lymphatic chains by immunolymphoscintigraphy or, more speculatively, for altering the status of regional immune function. The results presented here indicate that a low or intermediate antibody dose may optimize the signal:noise ratio for imaging. In Kk-negative animals, the percentage of dose taken up in the major organs was essentially independent of the dose administered; there was no evidence for saturable sites of nonspecific binding.

• Research Organization: National Cancer Institute, Bethesda, MD
• OSTI ID: 5619937
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States); ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DIAGNOSTIC USES
EFFICIENCY
INJECTION
INTAKE
LYMPH NODES
LYMPHATIC SYSTEM
MAMMALS
MICE
MOLECULAR WEIGHT
MONOCLONAL ANTIBODIES
RADIOISOTOPE SCANNING
RODENTS
SCINTISCANNING
USES
VERTEBRATES