Sensitivity of pretargeted immunoPET using 68Ga-peptide to detect colonic carcinoma liver metastases in a murine xenograft model: Comparison with 18FDG PET-CT

Abstract

// Fanny Foubert 1, 2 , Sébastien Gouard 1 , Catherine Saï-Maurel 1 , Michel Chérel 1, 3 , Alain Faivre-Chauvet 1, 4 , David M. Goldenberg 5, 6 , Jacques Barbet 1, 7 , Clément Bailly 1, 4 , Caroline Bodet-Milin 1, 3, 4 , Thomas Carlier 1, 4 , Françoise Kraeber-Bodéré 1, 3, 4 , Yann Touchefeu 1, 2, * and Eric Frampas 1, 8, * 1 CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France 2 Hepato-Gastroenterology Department, Institut des Maladies de l’Appareil Digestif, University Hospital, Nantes, France 3 Nuclear Medicine Department, ICO René Gauducheau Cancer Center, Saint Herblain, France 4 Nuclear Medicine Department, University Hospital, Nantes, France 5 IBC Pharmaceuticals Inc., Morris Plains, New Jersey, USA 6 Immunomedics Inc., Morris Plains, New Jersey, USA 7 GIP ARRONAX, Saint-Herblain, Nantes, France 8 Radiology Department, University Hospital, Nantes, France * These authors have contributed equally to this work Correspondence to: Eric Frampas, email: Eric.frampas@chu-nantes.fr Keywords: carcinoembryonic antigen; colonic cancer; liver metastases; 18 FDG-PET; immuno-PET Received: December 06, 2017      Accepted: May 12, 2018      Published: June 08, 2018 ABSTRACT Purpose: The aim of this study was to compare the performances pretargeted immunoPET 68 Ga-PETimaging ( 68 Ga-pPET) with anti carcino-embryonic antigen (CEA) and anti-histamine-succinyl-glycine (HSG) recombinant humanized bispecific monoclonal antibody (TF2) and 68 Ga-labeled HSG peptide (IMP288) to conventional 18 FDG-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 68 Ga-IMP288 24 hours later (n=8). Another group received 18 FDG (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 68 Ga-pPET compared to 18 FDG-PET ( P <0.05) with both imaging and biodistribution data. 68 Ga-pPET sensitivity for tumor detection was 67% vs. 31% with 18 FDG PET ( P =0.049). For tumors less than 200 mg, the sensitivity was 44% with 68 Ga-pPET vs. 0% for 18 FDG PET ( P =0.031). A strong correlation was demonstrated between tumor uptakes measured on PET images and biodistribution analyses (r 2 =0.85). Conclusion: 68 Ga-pPET was more sensitive than 18 FDG-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.