Pretargeted immunoscintigraphy: effect of hapten valency on murine tumor uptake.

Abstract

A method of radioimmunoscintigraphy using bivalent "Janus" haptens with an apparent enhanced affinity ("avidity") for the antibody is described. Janus with 50 micrograms pretargeted Mab WC3A11 resulted in significantly higher murine tumor concentrations (approximately 7%/g) compared to monovalent haptens (approximately 1.4%/g, p < 0.001), and the same high tumor-to-background ratios (approximately 3/1). Janus was synthesized by coupling two molecules of BABE together with a 1,4 butanedithiol linker. Janus itself was rapidly excreted (T1/2b = 42 min) by the kidneys and did not concentrate in any other organs or tissues. Three-step pretargeted immunoscintigraphy (binder, chaser, tracer) with 111In- or 67Ga-Co(III) Janus produced excellent mouse tumor images in 3 hr with high tumor-to-background ratios. The use of short-lived tracers, such as 99mTc and 68Ga, with a T1/2p of hours to image antibodies that localize slowly over several days in vivo is accessible with this new technology.

• Authors: D A Goodwin, C F Meares, M McTigue, W Chaovapong, C I Diamanti, C H Ransone, M J McCall
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 33 Issue 11 Pg. 2006-13 (Nov 1992) ISSN: 0161-5505 [Print] United States
• PMID: 1432163 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Gallium Radioisotopes
• Haptens
• Indium Radioisotopes

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Antibody Affinity
• Gallium Radioisotopes
• Half-Life
• Haptens (immunology)
• In Vitro Techniques
• Indium Radioisotopes
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental (diagnostic imaging)
• Radioimmunodetection (methods)