title: In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and (67/68Ga)-labeled haptens by pretargeting.
abstract: The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from patients with colorectal cancer with trivalent bispecific antibody TF2 and two hapten molecules, [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485 by means of pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala University Hospital, were frozen fresh and cryosectioned. The two hapten molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA) were labeled with (67)Ga or (68)Ga. The autoradiography was conducted by incubating the tissue samples with the bispecific antibody TF2, followed by washing and incubation with one of the radiolabeled hapten molecules. After washing, drying and exposure to phosphor imager plates, the autoradiograms were analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced binding was found in the tissue from colorectal cancer using the bispecific antibody TF2 and either of the haptens [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485. Distinct binding was also detected in the epithelium of most samples of neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is concluded that pretargeting CEA with the bispecific antibody TF2 followed by the addition of (67/68)Ga-labeled hapten is extremely sensitive for visualizing this marker for colorectal cancer. This methodology is therefore a very specific complement to other histochemical techniques in the diagnosis of biopsies or in samples taken from surgery. Use of the pretargeting technique in vivo may also be an advance in diagnosing patients with colorectal cancer, either using (67)Ga and SPECT or (68)Ga and PET.
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University Uppsala, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Hall
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blom
authors.forename: Johan
authors.initials: J
authors.lastname: Ulin
authors.forename: Azita
authors.initials: A
authors.lastname: Monazzam
authors.forename: Lars
authors.initials: L
authors.lastname: Påhlman
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.forename: Alkwin
authors.initials: A
authors.lastname: Wanders
authors.forename: William
authors.initials: W
authors.lastname: McBride
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
keywords: Autoradiography; CEA; Ga-67; Ga-68; carcinoembryonic antigen; colorectal cancer; pretargeting