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Current Radiopharmaceuticals

Editor-in-Chief

ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

99mTc-Labeled Nanobodies: A New Type of Targeted Probes for Imaging Antigen Expression

Author(s): Vicky Caveliers, Virna Cortez-Retamozo, Tony Lahoutte, Lea Olive Tchouate Gainkam, Sophie Hernot, Ann Packeu, Filip De Vos, Chris Vanhove, Serge Muyldermans, Patrick De Baetselier and Hilde Revets

Volume 1, Issue 1, 2008

Page: [37 - 41] Pages: 5

DOI: 10.2174/1874471010801010037

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Abstract

Introduction: The development of specific radiolabeled probes towards molecular markers in vivo has gained interest as targeted imaging allows for a more accurate detection of diseases. We investigate the feasibility of targeted imaging of cancer antigens using the variable domain of single chain camelid antibodies (Nanobodies®) labeled with 99mTechnetium. Nanobodies against carcinoembryonic antigen (CEA) were used as a model. Methods: His6-CEA1 Nanobodies were generated and labeled with 99mTc at their His-tag using Tc(I)-tricarbonyl (Isolink, Mallinckrodt, B.V., Petten, The Netherlands). The normal biodistribution was assessed in healthy athymic mice by ex vivo analysis at 1 and 3 h. In vivo targeting was evaluated in the same mouse model bearing the CEA-positive LS174T tumour or a CEA-negative A431 (human skin carcinoma) control tumour. Pinhole SPECT imaging was performed at 3 hours after intravenous injection of 90 MBq 99mTc-His6-CEA1 using a dual-headed gamma camera equipped with pinhole collimators. Results: Radiolabeling efficiency was > 95%. General biodistribution showed intense renal uptake and marked liver accumulation. Using pinhole-SPECT, the average uptake of 99mTc- His6-CEA1 in LS174T (CEA positive) was significantly higher compared to the A431 (CEA negative) control tumour: respectively 3.2 ± 0.6 %IA/cm3 and 1.1 ± 0.2 %IA/cm3 (p < 0.05). Conclusion: This study presents effective labeling of Nanobodies with 99mTc using Tc(I)-carbonyl chemistry and shows their potential as a new type of specific probes for imaging antigen expression.

Keywords: Nanobody, carcinoembryonic antigen, Tc(I)-carbonyl chemistry, imaging, tumor targeting


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