Biodistribution and tumor imaging of an anti-CEA single-chain antibody-albumin fusion protein
| Autor: | Desiree Crow, Thewodros Kassa, Paul J. Yazaki, David Colcher, James R. Bading, Andrew Raubitschek, Chia-Wei Cheung, Anne-Line Anderson, Mark A. Sherman |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Biodistribution Pathology medicine.medical_specialty Immunoconjugates Antibodies Neoplasm Recombinant Fusion Proteins Transplantation Heterologous Immunoglobulin Variable Region Mice Nude Article Iodine Radioisotopes Mice Carcinoembryonic antigen Antigen In vivo Albumins medicine Animals Humans Radiology Nuclear Medicine and imaging Tissue Distribution biology Chemistry Indium Radioisotopes Albumin Molecular biology Fusion protein Carcinoembryonic Antigen Transplantation Radioimmunodetection Positron-Emission Tomography biology.protein Molecular Medicine Female Antibody Radiopharmaceuticals Colorectal Neoplasms Neoplasm Transplantation |
| Zdroj: | Nuclear medicine and biology. 35(2) |
| ISSN: | 0969-8051 |
| Popis: | 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 [125 I]-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 [111 In]-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 [64 Cu]-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. |
| Databáze: | OpenAIRE |
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