Charalambos Tsoukalas1, Simonetta Geninatti-Crich2, Anastasios Gaitanis3, Theodoros Tsotakos1, Maria Paravatou-Petsotas1, Silvio Aime2, Rogelio Jiménez-Juárez4,5, Constantinos D Anagnostopoulos3, Kristina Djanashvili5, Penelope Bouziotis6. 1. Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", Aghia Paraskevi, 153 10, Athens, Greece. 2. Department of Molecular Biotechnology and Health Sciences, University of Turin, via Nizza 52, Torino, Italy. 3. Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Street, 115 27, Athens, Greece. 4. Department of Organic Chemistry, National School of Biological Sciences, National Polytechnical Institute, Prolongación de Carpio y Plan de Ayala S/N, 11340, Mexico D.F., Mexico. 5. Department of Biotechnology, Delft University of Technology, Van der Maasweg, 2629 HZ, Delft, Netherlands. 6. Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", Aghia Paraskevi, 153 10, Athens, Greece. bouzioti@rrp.demokritos.gr.
Abstract
PURPOSE: The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia). PROCEDURES: The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [68Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCID mice injected with [68Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent. RESULTS: The affinity of [68Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [68Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection. CONCLUSIONS: Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.
PURPOSE: The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia). PROCEDURES: The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [68Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCIDmice injected with [68Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent. RESULTS: The affinity of [68Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCIDmice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [68Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection. CONCLUSIONS: Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.
Authors: Aurélie Cazet; Sylvain Julien; Marie Bobowski; Marie-Ange Krzewinski-Recchi; Anne Harduin-Lepers; Sophie Groux-Degroote; Philippe Delannoy Journal: Carbohydr Res Date: 2010-02-04 Impact factor: 2.104
Authors: Kristina Djanashvili; Gerben A Koning; Astrid J G M van der Meer; Hubert Th Wolterbeek; Joop A Peters Journal: Contrast Media Mol Imaging Date: 2007 Jan-Feb Impact factor: 3.161
Authors: Barbara J Fueger; Johannes Czernin; Isabel Hildebrandt; Chris Tran; Benjamin S Halpern; David Stout; Michael E Phelps; Wolfgang A Weber Journal: J Nucl Med Date: 2006-06 Impact factor: 10.057