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.
(18)F-Fluorodeoxyglucose ((18)F-FDG) is the most common molecular imaging agent in oncology, with a high sensitivity and specificity for detecting several cancers. Antibodies could enhance specificity; therefore, procedures were developed for radiolabeling a small ( approximately 1451 Da) hapten peptide with (68)Ga or (18)F to compare their specificity with (18)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 x 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)F-labeled IMP-449 distributed similarly in the tumor and normal tissues as the (68)Ga-labeled IMP-288, indicating that either radiolabeled hapten peptide could be used. Thus, pretargeted immuno-PET does exceptionally well with short-lived radionuclides and is a highly sensitive procedure that is more specific than (18)F-FDG-PET. Mol Cancer Ther; 9(4); 1019-27. (c)2010 AACR.
Schoffelen
Rafke
R
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. r.schoffelen@nucmed.umcn.nl
Sharkey
Robert M
RM
Goldenberg
David M
DM
Franssen
Gerben
G
McBride
William J
WJ
Rossi
Edmund A
EA
Chang
Chien-Hsing
CH
Laverman
Peter
P
Disselhorst
Jonathan A
JA
Eek
Annemarie
A
van der Graaf
Winette T A
WT
Oyen
Wim J G
WJ
Boerman
Otto C
OC
D000818:Animals; D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes; D006241:Haptens / Q000276:immunology*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D049268:Positron-Emission Tomography; D014018:Tissue Distribution / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen; C515662:DOTA-tyrosyl-lysyl(histaminyl-succinyl-glycyl)-glutamyl-lysyl(histaminyl-succinyl-glycyl)amide; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D006241:Haptens; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D019788:Fluorodeoxyglucose F18