title: Biodistribution and tumor imaging of an anti-CEA single-chain antibody-albumin fusion protein.
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 [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.
authors.affiliation: Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA. pyazaki@coh.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Yazaki
authors.forename: Thewodros
authors.initials: T
authors.lastname: Kassa
authors.forename: Chia-wei
authors.initials: CW
authors.lastname: Cheung
authors.forename: Desiree M
authors.initials: DM
authors.lastname: Crow
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sherman
authors.forename: James R
authors.initials: JR
authors.lastname: Bading
authors.forename: Anne-Line J
authors.initials: AL
authors.lastname: Anderson
authors.forename: David
authors.initials: D
authors.lastname: Colcher
authors.forename: Andrew
authors.initials: A
authors.lastname: Raubitschek
mesh_terms: D000418:Albumins / Q000235:genetics / Q000493:pharmacokinetics*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods; D016719:Radioimmunodetection / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000276:immunology; D014183:Transplantation, Heterologous
chemical_list: D000418:Albumins; D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D007135:Immunoglobulin Variable Region; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins