HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wall, J. S. Articles by Solomon, A. Search for Related Content PubMed PubMed Citation Articles by Wall, J. S. Articles by Solomon, A.

Radioimaging of Light Chain Amyloid with a Fibril-Reactive Monoclonal Antibody

¹ Human Immunology and Cancer Program, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee; ² Engineering Science and Technology Group, Oak Ridge National Laboratory, Oak Ridge, Tennessee; ³ Department of Computer Science, University of Tennessee, Knoxville, Tennessee; and ⁴ Cancer Imaging and Tracer Development Research Program, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee

Correspondence: For correspondence or reprints contact: Jonathan S. Wall, PhD, University of Tennessee Graduate School of Medicine, 1924 Alcoa Hwy., Knoxville, TN 37920. E-mail: jwall{at}mc.utmck.edu

Currently, there are no available means in the United States to document objectively the location and extent of amyloid deposits in patients with systemic forms of amyloidosis. To address this limitation, we have developed a novel diagnostic strategy, namely, the use of a radiolabeled fibril-reactive murine monoclonal antibody (mAb) as an amyloid-specific imaging agent. The goal of this study was to determine the pharmacokinetics, biodistribution, and ability of this reagent to target the type of amyloid that is formed from immunoglobulin light chains, that is, AL. Methods: Subcutaneous tumors (amyloidomas) were induced in BALB/c mice by injection of human AL fibrils. The IgG1 mAb designated 11-1F4 and an isotype-matched control antibody were radioiodinated, and the pharmacokinetics and localization of these reagents were determined from blood and tissue samples. Amyloidoma-bearing animals that received ¹²⁵I- or ¹²⁴I-labeled antibodies were imaged by whole-body small-animal SPECT/CT or small-animal PET/CT technology, respectively. Results: Radioiodinated mAb 11-1F4 retained immunoreactivity, as evidenced by its subnanomolar affinity for light chains immobilized on 96-well microtiter plates and for beads conjugated with a light chain–related peptide. Additionally, after intravenous administration, the labeled reagents had the expected biologic half-life of murine IgG1, with monoexponential whole-body clearance kinetics. In the amyloidoma mouse model, ¹²⁵I-11-1F4 was predominately localized in the tumors, as demonstrated in biodistribution and autoradiographic analyses. The mean uptake of this reagent, that is, the percentage injected dose per gram of tissue, 72 h after injection was significantly higher for amyloid than for skeletal muscle, spleen, kidney, heart, liver, or other tissue samples. Notably, the accumulation within the amyloidomas of ¹²⁵I- or ¹²⁴I-11-1F4 was readily visible in the fused small-animal SPECT/CT or small-animal PET/CT images, respectively. Conclusion: Our studies demonstrate the amyloid-imaging capability of a radiolabeled fibril-reactive mAb and provide the basis for a clinical trial designed to determine its diagnostic potential in patients with AL amyloidosis and other systemic amyloidoses.

Key Words: amyloid • immunoimaging • small-animal SPECT/CT • small-animal PET/CT

COPYRIGHT © 2006 by the Society of Nuclear Medicine, Inc.

Related articles in JNM:

This Month in JNM

JNM 2006 47: 9a-10a. [Full Text]  

This article has been cited by other articles:

				B. P.C. Hazenberg, M. H. van Rijswijk, M. N. Lub-de Hooge, E. Vellenga, E. B. Haagsma, M. D. Posthumus, and P. L. Jager Diagnostic Performance and Prognostic Value of Extravascular Retention of 123I-Labeled Serum Amyloid P Component in Systemic Amyloidosis J. Nucl. Med., June 1, 2007; 48(6): 865 - 872. [Abstract] [Full Text] [PDF]