Sensitivity of pretargeted immunoPET using 68Ga-peptide to detect colonic carcinoma liver metastases in a murine xenograft model: Comparison with 18FDG PET-CT
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Fanny Foubert1,2, Sébastien Gouard1, Catherine Saï-Maurel1, Michel Chérel1,3, Alain Faivre-Chauvet1,4, David M. Goldenberg5,6, Jacques Barbet1,7, Clément Bailly1,4, Caroline Bodet-Milin1,3,4, Thomas Carlier1,4, Françoise Kraeber-Bodéré1,3,4, Yann Touchefeu1,2,* and Eric Frampas1,8,*
1CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France
2Hepato-Gastroenterology Department, Institut des Maladies de l’Appareil Digestif, University Hospital, Nantes, France
3Nuclear Medicine Department, ICO René Gauducheau Cancer Center, Saint Herblain, France
4Nuclear Medicine Department, University Hospital, Nantes, France
5IBC Pharmaceuticals Inc., Morris Plains, New Jersey, USA
6Immunomedics Inc., Morris Plains, New Jersey, USA
7GIP ARRONAX, Saint-Herblain, Nantes, France
8Radiology Department, University Hospital, Nantes, France
*These authors have contributed equally to this work
Eric Frampas, email: Eric.firstname.lastname@example.org
Keywords: carcinoembryonic antigen; colonic cancer; liver metastases; 18FDG-PET; immuno-PET
Received: December 06, 2017 Accepted: May 12, 2018 Published: June 08, 2018
Purpose: The aim of this study was to compare the performances pretargeted immunoPET 68Ga-PETimaging (68Ga-pPET) with anti carcino-embryonic antigen (CEA) and anti-histamine-succinyl-glycine (HSG) recombinant humanized bispecific monoclonal antibody (TF2) and 68Ga-labeled HSG peptide (IMP288) to conventional 18FDG-PET in an orthotopic murine model of liver metastases of human colonic cancer.
Methods: Hepatic tumor burden following intra-portal injection of luciferase-transfected LS174T cells in nude mice was confirmed using bioluminescence. One group of animals was injected intravenously with TF2 and with 68Ga-IMP288 24 hours later (n=8). Another group received 18FDG (n=8), and a third had both imaging modalities (n=7). PET acquisitions started 1 hour after injection of the radioconjugate. Biodistributions in tumors and normal tissues were assessed one hour after imaging.
Results: Tumor/organ ratios were significantly higher with 68Ga-pPET compared to 18FDG-PET (P<0.05) with both imaging and biodistribution data. 68Ga-pPET sensitivity for tumor detection was 67% vs. 31% with 18FDG PET (P=0.049). For tumors less than 200 mg, the sensitivity was 44% with 68Ga-pPET vs. 0% for 18FDG PET (P=0.031). A strong correlation was demonstrated between tumor uptakes measured on PET images and biodistribution analyses (r2=0.85).
Conclusion: 68Ga-pPET was more sensitive than 18FDG-PET for the detection of human colonic liver metastases in an orthotopic murine xenograft model. Improved tumor/organ ratios support the use of pretargeting method for imaging and therapy of CEA-expressing tumors.
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