Abstract A32: Pretargeted immunoPET of CEA-expressing in intraperitoneal human colonic tumor xenografts in nude mice

Abstract

Abstract Objective: Radiolabeled antibodies were being developed commercially for the detection of several cancer types. However, imaging with radiolabeled antibodies require a relatively long interval between injection and imaging acquisition for adequate contrast to develop. The pretargeting method is a 2-step method: a unlabeled bsMAb with affinity for the tumor and a small radiolabeled molecule is injected, followed by the a radiolabeled compound. This aims to optimize the imaging system by specific tumor accumulation and fast blood clearance of the radiopharmacon, which allows imaging within one hour. Short-lived positron emitting radionuclides, e.g. 68Ga (half life: 68 min) match the pharmacokinetics of the small molecule. In this study, pretargeted immunoPET with a bispecific monoclonal anti-carcinoembryonic antigen (CEA) x anti-histamine-succinyl-glycine (HSG) antibody, TF2, and a radiolabeled peptide, IMP288, was compared to 18F-FDG in detecting CEA-expressing tumors in nude mice. Methods: Groups of five BALB/c nude mice were inoculated with CEA-expressing human colonic tumor cells intraperitoneally. One group received 5 MBq 18F-FDG intravenously (i.v.). Another group received TF2 and 5 MBq 68Ga-IMP288 i.v. 16 h later. After one hour PET/CT images were acquired. One day later this was repeated vice versa. Uptake of 68Ga-IMP288 or 18F-FDG in the tumors and other dissected tissues was determined. Results: High, specific tumor uptake of 68Ga-IMP288 (23.4 ± 7.2% ID/g) was observed, with very low accretion in the normal tissues (intestines: 0.50 ± 0.19 % ID/g; liver: 1.83 ± 0.45 % ID/g). This resulted in high tumor-to-background ratios (e.g. tumor-to-intestines 57.5 ± 22.4) and in the clear visualization of the small intra-abdominal tumor lesions (1.5–5 mm), as soon as one hour after the injection of 68Ga-IMP288. 18F-FDG localized efficiently in the tumors (8.7 ± 3.1 % ID/g), but with physiological uptake in various normal tissues (intestines: 2.15 ± 0.61 % ID/g; liver: 2.78 ± 0.52 % ID/g). The low tumor-to-background ratio (e.g. tumor-to-intestines 4.0 ± 0.9) complicated the detection of the tumors. Conclusions: This study indicated that pretargeted immunoPET with TF2 and 68Ga-IMP288 is a specific and sensitive method for detecting colon cancer. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A32