Anti-CEA Pretargeted Immuno-PET Shows Higher Sensitivity Than DOPA PET/CT in Detecting Relapsing Metastatic Medullary Thyroid Carcinoma: Post Hoc Analysis of the iPET-MTC Study

Abstract

Pretargeting parameters for the use of anti-carcinoembryonic antigen (CEA) bispecific monoclonal antibody TF2 and the ⁶⁸Ga-labeled IMP288 peptide for immuno-PET have been optimized in a first-in-humans study performed on medullary thyroid carcinoma (MTC) patients (the iPET-MTC study). The aim of this post hoc analysis was to determine the sensitivity of immuno-PET in relapsing MTC patients, in comparison with conventional imaging and ¹⁸F-l-dihydroxyphenylalanine (¹⁸F-DOPA) PET/CT. Methods: Twenty-five studies were analyzed in 22 patients. All patients underwent immuno-PET 1 and 2 h after ⁶⁸Ga-IMP288 injection pretargeted by TF2, in addition to neck, thoracic, abdominal, and pelvic CT; bone and liver MRI; and ¹⁸F-DOPA PET/CT. The gold standard was histology or confirmation by one other imaging method or by imaging follow-up. Results: In total, 190 lesions were confirmed by the gold standard: 89 in lymph nodes, 14 in lungs, 46 in liver, 37 in bone, and 4 in other sites (subcutaneous tissue, heart, brain, and pancreas). The number of abnormal foci detected by immuno-PET was 210. Among these, 174 (83%) were confirmed as true-positive by the gold standard. Immuno-PET showed a higher overall sensitivity (92%) than ¹⁸F-DOPA PET/CT (65%). Regarding metastatic sites, immuno-PET had a higher sensitivity than CT, ¹⁸F-DOPA PET/CT, or MRI for lymph nodes (98% vs. 83% for CT and 70% for ¹⁸F-DOPA PET/CT), liver (98% vs. 87% for CT, 65% for ¹⁸F-DOPA PET/CT, and 89% for MRI), and bone (92% vs. 64% for ¹⁸F-DOPA PET/CT and 86% for MRI), whereas sensitivity was lower for lung metastases (29% vs. 100% for CT and 14% for ¹⁸F-DOPA PET/CT). Tumor SUV_max at 60 min ranged from 1.2 to 59.0, with intra- and interpatient variability. Conclusion: This post hoc study demonstrates that anti-carcinoembryonic antigen immuno-PET is an effective procedure for detecting metastatic MTC lesions. Immuno-PET showed a higher overall sensitivity than ¹⁸F-DOPA PET/CT for disclosing metastases, except for the lung, where CT remains the most effective examination.

Keywords: MTC; bispecific antibody; carcinoembryonic antigen; immuno-PET; pretargeted radioimmunoimaging.