Biodistribution and tumor imaging of an anti-CEA single-chain antibody–albumin fusion protein

Yazaki, Paul J.; Kassa, Thewodros; Cheung, Chia-wei; Crow, Desiree M.; Sherman, Mark A.; Bading, James R.; Anderson, Anne-Line J.; Colcher, David; Raubitschek, Andrew

doi:10.1016/j.nucmedbio.2007.10.010

Next »Nuclear Medicine and Biology
Volume 35, Issue 2 , Pages 151-158, February 2008

Biodistribution and tumor imaging of an anti-CEA single-chain antibody–albumin fusion protein☆

Paul J. Yazaki
- Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
- Corresponding author. Tel.: +1 626 256 4673; fax: +1 626 301 8280.
Thewodros Kassa
- Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
Chia-wei Cheung
- Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
Desiree M. Crow
- Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
Mark A. Sherman
- Division of Information Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
James R. Bading
- Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
Anne-Line J. Anderson
- Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
David Colcher
- Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
Andrew Raubitschek
- Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA

Received 15 August 2007; received in revised form 19 October 2007; accepted 24 October 2007.

Abstract

Albumin fusion proteins have demonstrated the ability to prolong the in vivo half-life of small therapeutic proteins/peptides in the circulation and thereby potentially increase their therapeutic efficacy. To evaluate if this format can be employed for antibody-based imaging, an anticarcinoembryonic antigen (CEA) single-chain antibody(scFv)–albumin fusion protein was designed, expressed and radiolabeled for biodistribution and imaging studies in athymic mice bearing human colorectal carcinoma LS-174T xenografts. The [¹²⁵I]-T84.66 fusion protein demonstrated rapid tumor uptake of 12.3% injected dose per gram (ID/g) at 4 h that reached a plateau of 22.7% ID/g by 18 h. This was a dramatic increase in tumor uptake compared to 4.9% ID/g for the scFv alone. The radiometal [¹¹¹In]-labeled version resulted in higher tumor uptake, 37.2% ID/g at 18 h, which persisted at the tumor site with tumor: blood ratios reaching 18:1 and with normal tissues showing limited uptake. Based on these favorable imaging properties, a pilot [⁶⁴Cu]-positron emission tomography imaging study was performed with promising results.

The anti-CEA T84.66 scFv–albumin fusion protein demonstrates highly specific tumor uptake that is comparable to cognate recombinant antibody fragments. The radiometal-labeled version, which shows lower normal tissue accumulation than these recombinant antibodies, provides a promising and novel platform for antibody-based imaging agents.

Keywords: Albumin-fusion protein, CEA, Colorectal cancer, Imaging