title: Quantitative immuno-positron emission tomography imaging of HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody.
abstract: Positron emission tomography (PET) provides an effective means of both diagnosing/staging several types of cancer and evaluating efficacy of treatment. To date, the only U.S. Food and Drug Administration-approved radiotracer for oncologic PET is (18)F-fluoro-deoxyglucose, which measures glucose accumulation as a surrogate for malignant activity. Engineered antibody fragments have been developed with the appropriate targeting specificity and systemic elimination properties predicted to allow for effective imaging of cancer based on expression of tumor associated antigens. We evaluated a small engineered antibody fragment specific for the HER2 receptor tyrosine kinase (C6.5 diabody) for its ability to function as a PET radiotracer when labeled with iodine-124. Our studies revealed HER2-dependent imaging of mouse tumor xenografts with a time-dependent increase in tumor-to-background signal over the course of the experiments. Radioiodination via an indirect method attenuated uptake of radioiodine in tissues that express the Na/I symporter without affecting the ability to image the tumor xenografts. In addition, we validated a method for using a clinical PET/computed tomography scanner to quantify tumor uptake in small-animal model systems; quantitation of the tumor targeting by PET correlated with traditional necropsy-based analysis at all time points analyzed. Thus, diabodies may represent an effective molecular structure for development of novel PET radiotracers.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Robinson
authors.forename: Mohan
authors.initials: M
authors.lastname: Doss
authors.forename: Calvin
authors.initials: C
authors.lastname: Shaller
authors.forename: Deepa
authors.initials: D
authors.lastname: Narayanan
authors.forename: James D
authors.initials: JD
authors.lastname: Marks
authors.forename: Lee P
authors.initials: LP
authors.lastname: Adler
authors.forename: Dinko E
authors.initials: DE
authors.lastname: González Trotter
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Adams
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000493:pharmacokinetics; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases