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Exp Clin Endocrinol Diabetes 2005; 113(7): 381-387
DOI: 10.1055/s-2005-865716
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Quantitative Evaluation of a Monoclonal Antibody and its Fragment as Potential Markers for Pancreatic Beta Cell Mass

C. S. Hampe1 , A. R. Wallen1 , M. Schlosser2 , M. Ziegler3 , I. R. Sweet1
  • 1Department of Medicine, University of Washington, Seattle, Washington, USA
  • 2Institute of Pathophysiology, Ernst Moritz Arndt University of Greifswald, Karlsburg, Germany
  • 3Institute of Diabetes „Gerhardt Katsch“, Karlsburg, Germany
Further Information

Publication History

Received: October 13, 2004 First decision: February 2, 2005

Accepted: April 28, 2005

Publication Date:
18 July 2005 (online)

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Abstract

Antibodies, due to their high specificities and retention, represent potential beta cell imaging agents, however their slow clearance from the blood may preclude their use. Antibody fragments (Fabs) have much higher clearance and if they can be made with similar binding characteristics, would be more efficacious agents. An existing beta cell specific antibody (K14D10) and its Fab were evaluated with a previously developed screening assay. The Fab and the intact immunoglobulin (IgG) had similar affinities (6 - 20 nM), binding sites (300 000 - 700 000 sites/cell), and binding kinetics (t1/2 = 8 - 18 minutes) for beta cells. However, the cellular specificity was far below the estimated requisite values needed to overcome the very low beta cell mass in the pancreas. The Fab cleared the blood twice as fast as the IgG, but did not preferentially accumulate into pancreas. Thus, generation of Fabs from IgGs with high beta cell binding and blood clearance appears feasible, but in order for molecules to be useful for tracking beta cell mass, antibodies of greater cellular specificity will have to be used.

Key words

Beta cell mass - monoclonal antibodies - Fab - PET

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Ian R. Sweet

University of Washington

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Email: isweet@u.washington.edu