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In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and 67/68Ga-labeled haptens by pretargeting
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
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2012 (English)In: American journal of nuclear medicine and molecular imaging, ISSN 2160-8407, Vol. 2, no 2, 141-150 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2012. Vol. 2, no 2, 141-150 p.
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Medicinal Chemistry Pharmaceutical Sciences Natural Sciences
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URN: urn:nbn:se:uu:diva-188959PubMedID: 23133809OAI: oai:DiVA.org:uu-188959DiVA: diva2:580292
Available from: 2012-12-21 Created: 2012-12-21 Last updated: 2015-03-25Bibliographically approved

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PubMedhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477725/

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Hall, HåkanVelikyan, IrinaMonazzam, AzitaPåhlman, LarsMicke, PatrickWanders, AlkwinLångström, Bengt

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Hall, HåkanVelikyan, IrinaMonazzam, AzitaPåhlman, LarsMicke, PatrickWanders, AlkwinLångström, Bengt
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Preclinical PET PlatformBiomedical Radiation SciencesDepartment of Biochemistry and Organic ChemistryColorectal SurgeryMolecular and Morphological Pathology
Medicinal ChemistryPharmaceutical SciencesNatural Sciences

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