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Am J Nucl Med Mol Imaging 2012;2(2):141-150.
Original Article
In vitro autoradiography of carcinoembryonic antigen in tissue from patients with
colorectal cancer using multifunctional antibody TF2 and 68/67Ga-labeled haptens
by pretargeting
Hakan Hall, Irina Velikyan, Elisabeth Blom, Johan Ulin, Azita Monazzam, Lars Pahlman, Patrick Micke, Alkwin Wanders, William
McBride, David M. Goldenberg, Bengt Langstrom
Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala, Sweden; Department of Radiology,
Oncology and Radiation Science, Uppsala University, Uppsala, Sweden; Uppsala PET Center, Uppsala University Hospital,
Uppsala, Sweden; Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden; Odense University
Hospital, Department of Nuclear Medicine, PET & Cyclotron Unit, University of Southern Denmark, Institute of Clinical Research,
Odense, Denmark; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Oncology and Pathology,
Uppsala University, Uppsala, Sweden; Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains,
New Jersey, USA; Imperial College, Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, London, UK
Received November 29, 2011; accepted December 5, 2011; Epub March 28, 2012; Published April 15, 2012
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, [67/68Ga]Ga-IMP461 and [67/68Ga]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 67Ga or 68Ga. 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 [67/68Ga]Ga-IMP461 and
[67/68Ga]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 67/68Ga-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
67Ga and SPECT or 68Ga and PET. (ajnmmi1111004).
Keywords: Autoradiography, carcinoembryonic antigen, CEA, colorectal cancer, Ga-67, Ga-68, pretargeting
Address all correspondence to:
Dr. Hakan Hall
Department of Medicinal Chemistry, Preclinical PET Platform
Uppsala University, Dag Hammarskjölds väg 14C
Uppsala Science Park, SE-751 83 Uppsala, Sweden.
Tel: +46 (0)18 471 5309
E-mail: hakan.hall@pet.medchem.uu.se
Original Article
In vitro autoradiography of carcinoembryonic antigen in tissue from patients with
colorectal cancer using multifunctional antibody TF2 and 68/67Ga-labeled haptens
by pretargeting
Hakan Hall, Irina Velikyan, Elisabeth Blom, Johan Ulin, Azita Monazzam, Lars Pahlman, Patrick Micke, Alkwin Wanders, William
McBride, David M. Goldenberg, Bengt Langstrom
Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala, Sweden; Department of Radiology,
Oncology and Radiation Science, Uppsala University, Uppsala, Sweden; Uppsala PET Center, Uppsala University Hospital,
Uppsala, Sweden; Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden; Odense University
Hospital, Department of Nuclear Medicine, PET & Cyclotron Unit, University of Southern Denmark, Institute of Clinical Research,
Odense, Denmark; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Oncology and Pathology,
Uppsala University, Uppsala, Sweden; Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains,
New Jersey, USA; Imperial College, Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, London, UK
Received November 29, 2011; accepted December 5, 2011; Epub March 28, 2012; Published April 15, 2012
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, [67/68Ga]Ga-IMP461 and [67/68Ga]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 67Ga or 68Ga. 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 [67/68Ga]Ga-IMP461 and
[67/68Ga]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 67/68Ga-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
67Ga and SPECT or 68Ga and PET. (ajnmmi1111004).
Keywords: Autoradiography, carcinoembryonic antigen, CEA, colorectal cancer, Ga-67, Ga-68, pretargeting
Address all correspondence to:
Dr. Hakan Hall
Department of Medicinal Chemistry, Preclinical PET Platform
Uppsala University, Dag Hammarskjölds väg 14C
Uppsala Science Park, SE-751 83 Uppsala, Sweden.
Tel: +46 (0)18 471 5309
E-mail: hakan.hall@pet.medchem.uu.se
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