Pretargeted Immuno–Positron Emission Tomography Imaging of Carcinoembryonic Antigen–Expressing Tumors with a Bispecific Antibody and a 68Ga- and 18F-Labeled Hapten Peptide in Mice with Human Tumor Xenografts

Abstract

F-FDG for detecting tumors using a pretargeting procedure. Mice were implanted with carcinoembryonic antigen (CEA; CEACAM5)-expressing LS174T human colonic tumors and a CEA-negative tumor, or an inflammation was induced in thigh muscle. A bispecific monoclonal anti-CEA × anti-hapten antibody was given to mice, and 16 hours later, 5 MBq of 68 Ga-or 18 F-labeled hapten peptides were administered intravenously. Within 1 hour, tissues showed high and specific targeting of 68 Ga-IMP-288, with 10.7 ± 3.6% ID/g uptake in the tumor and very low uptake in normal tissues (e.g., tumor-to-blood ratio of 69.9 ± 32.3), in a CEA-negative tumor (0.35 ± 0.35% ID/g), and inflamed muscle (0.72 ± 0.20% ID/g). 18 F-FDG localized efficiently in the tumor (7.42 ± 0.20% ID/g) but also in the inflamed muscle (4.07 ± 1.13% ID/g) and in several normal tissues; thus, pretargeted 68 Ga-IMP-288 provided better specificity and sensitivity.Positron emission tomography (PET)/computed tomography images reinforced the improved specificity of the pretargeting method.18

Pretargeted 177Lu Radioimmunotherapy of Carcinoembryonic Antigen–Expressing Human Colonic Tumors in Mice

“…In this model system, in which small tumor xenografts were used, the amount of radioactivity that could be delivered in a single treatment was limited by the amount and specific activity of IMP288 that could be given with antigen-saturating amounts of the bsMAb. We recently reported an evaluation of this same pretargeting system for PET using 68 Ga-and 18 F-labeled peptides (18) and found, as in that study, that 5 nmol (800 mg) of TF2 saturated the amount of antigen in LS174T tumors. Thus, this amount of bsmAb is the upper limit that should be used in this pretargeting setting (28).…”

“…IMP288 was labeled with 111 In (Covidien) at a specific activity of 32 MBq/nmol and with 177 Lu (IDB Holland BV) at a specific activity of 86 MBq/nmol, and radiolabeling was performed as described previously (18).…”

“…Furthermore, 111 In-IMP288 and 177 Lu-IMP288 were analyzed by reversed-phase high-performance liquid chromatography as described previously (18).…”

“…Thus, the peptide can be radiolabeled stably with a variety of radionuclides, such as 111 In and 99m Tc for SPECT (13); 18 F and 68 Ga for PET (15)(16)(17)(18); or 131 I, 90 Y, and 177 Lu for pretargeted radioimmunotherapy (PRIT) (19).…”

Pretargeted Radioimmunotherapy of Prostate Cancer with an Anti-TROP-2×Anti-HSG Bispecific Antibody and a 177Lu-Labeled Peptide

“…Radiolabeling was performed essentially as described previously by Schoffelen et al 12 Prior to i.v. injection, the preparation was diluted at least 2.5 times with 0.5% bovine serum albumin (BSA; Sigma-Aldrich) in phosphate-buffered saline (PBS).…”