Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody

Jonathan Wall, Stephen Kennel, Mike Paulus, Jens Gregor, Tina Richey, James Avenell, Jeffrey Yap, David Townsend, Deborah T. Weiss, Alan Solomon

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 wholebody 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.

Original languageEnglish (US)
Pages (from-to)2016-2024
Number of pages9
JournalJournal of Nuclear Medicine
Volume47
Issue number12
StatePublished - Dec 1 2006

Fingerprint

Amyloid
Monoclonal Antibodies
Light
Amyloidosis
Pharmacokinetics
Immunoglobulin G
Immunoglobulin Light Chains
Injections
Antibodies
Amyloid Plaques
Intravenous Administration
Half-Life
Neoplasms
Skeletal Muscle
Spleen
Clinical Trials
Technology
Kidney
Peptides
Liver

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody. / Wall, Jonathan; Kennel, Stephen; Paulus, Mike; Gregor, Jens; Richey, Tina; Avenell, James; Yap, Jeffrey; Townsend, David; Weiss, Deborah T.; Solomon, Alan.

In: Journal of Nuclear Medicine, Vol. 47, No. 12, 01.12.2006, p. 2016-2024.

Research output: Contribution to journalArticle

Wall, J, Kennel, S, Paulus, M, Gregor, J, Richey, T, Avenell, J, Yap, J, Townsend, D, Weiss, DT & Solomon, A 2006, 'Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody', Journal of Nuclear Medicine, vol. 47, no. 12, pp. 2016-2024.
Wall, Jonathan ; Kennel, Stephen ; Paulus, Mike ; Gregor, Jens ; Richey, Tina ; Avenell, James ; Yap, Jeffrey ; Townsend, David ; Weiss, Deborah T. ; Solomon, Alan. / Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody. In: Journal of Nuclear Medicine. 2006 ; Vol. 47, No. 12. pp. 2016-2024.
@article{22f84d4b17224ff6a383b175fc022cc1,
title = "Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody",
abstract = "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 wholebody 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.",
author = "Jonathan Wall and Stephen Kennel and Mike Paulus and Jens Gregor and Tina Richey and James Avenell and Jeffrey Yap and David Townsend and Weiss, {Deborah T.} and Alan Solomon",
year = "2006",
month = "12",
day = "1",
language = "English (US)",
volume = "47",
pages = "2016--2024",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "12",

}

TY - JOUR

T1 - Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody

AU - Wall, Jonathan

AU - Kennel, Stephen

AU - Paulus, Mike

AU - Gregor, Jens

AU - Richey, Tina

AU - Avenell, James

AU - Yap, Jeffrey

AU - Townsend, David

AU - Weiss, Deborah T.

AU - Solomon, Alan

PY - 2006/12/1

Y1 - 2006/12/1

N2 - 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 wholebody 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.

AB - 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 wholebody 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.

UR - http://www.scopus.com/inward/record.url?scp=34250335813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250335813&partnerID=8YFLogxK

M3 - Article

VL - 47

SP - 2016

EP - 2024

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 12

ER -