Initial Clinical Results of a Novel Immuno-PET Theranostic Probe in HER2-negative Breast Cancer

Caroline Rousseau (1) , David M Goldenberg (2, 3) , Mathilde Colombié (4, 5) , Jean-Charles Sébille (4, 5) , Philippe Meingan (4, 6) , Ludovic Ferrer (1, 7, 4) , Pierre Baumgartner (4, 8) , Evelyne M Cerato (9) , Damien Masson (10) , Mario Campone (11, 4, 12) , Aurore Rauscher (8) , Vincent Fleury (5) , Catherine Labbé (6) , Alain Faivre-Chauvet (5, 12) , Jean-Sebastien Fresnel (4, 11) , Claire Toquet (13) , Jacques Barbet (14) , Robert M Sharkey (3) , Loïc Campion (15, 16) , Françoise Kraeber-Bodéré (1, 5)

1 CRCINA-ÉQUIPE 13 - Nuclear Oncology
2 IBC Pharmaceuticals Inc [Morris Plains, NJ, USA]
3 Immunomedics Inc. [Morris Plains, NJ, USA]
4 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
5 Service de Médecine Nucléaire [Nantes]
6 Service de Radiologie [Nantes]
7 GIP Arronax - Département de Physique [Nantes]
8 Pharmacie Centrale - PHU 11 Pharmacie [CHU Nantes]
9 (DRCI) - Délégation à la Recherche Clinique et à l'Enovation [Nantes]
10 Département de Biologie des Cancers [ICO, Nantes]
11 Institut d'oncologie de l'Ouest [CHU Nantes]
12 CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
13 Département de Pathologie [CHU Nantes]
14 Institut de Recherche Public - ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain]
15 CRCINA-ÉQUIPE 11 - Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression
16 Hôtel Dieu - Plateforme de Biométrie [CHU Nantes]

Purpose: This prospective study evaluated the imaging performance of a novel immunological pretargeting positron-emission tomorgraphy (immuno-PET) method in patients with HER2-negative, carcinoembryonic antigen (CEA)-positive, metastatic breast cancer (BC), compared to computed tomography (CT), bone magnetic resonance imaging (MRI), and 18Fluorodeoxyglucose PET (FDG-PET). Patients and Methods: Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq 68Ga-IMP288, a histamine-succinyl-glycine peptide given following initial targeting of a trivalent anti-CEA, bispecific, anti-peptide antibody. The gold standards were histology and imaging follow-up. Tumor standard uptake values (SUVmax and SUVmean) were measured, and tumor burden analyzed using Total Tumor Volume (TTV) and Total Lesion Activity (TLA). Results: Total lesion sensitivity of immuno-PET and FDG-PET was 94.7% (1116/1178) and 89.6% (1056/1178), respectively. Immuno-PET had a somewhat higher sensitivity than CT and FDG-PET in lymph nodes (92.4% vs 69.7% and 89.4%, respectively) and liver metastases (97.3% vs 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI and FDG-PET for bone lesions (95.8% vs 90.7% and 89.3%, respectively). In contrast to FDG-PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUVmax, SUVmean, and TTV, TLA was significantly higher with immuno-PET compared to FDG PET (P = 0.009). Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by 68Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive, metastatic BC patients, and warrants further research.

Mots clés: bispecific antibody; Radioimmunoimaging; Oncology: Breast; PET/CT; Breast cancer; Immuno-PET; gallium-68; pretargeting

Domaines: Cancer

Caroline Rousseau, David M Goldenberg, Mathilde Colombié, Jean-Charles Sébille, Philippe Meingan, et al.. Initial Clinical Results of a Novel Immuno-PET Theranostic Probe in HER2-negative Breast Cancer. Journal of Nuclear Medicine, 2020, pp.jnumed.119.236000. ⟨10.2967/jnumed.119.236000⟩. ⟨inserm-02512957⟩