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

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

Sensitivities evaluation of five radiopharmaceuticals in four common medullary thyroid carcinoma metastatic sites on PET/CT: a network meta-analysis and systematic review

“…After the comprehensive computerized search was performed and references lists were extensively crosschecked, our research yielded 1618 records on or before April 11, 2022, including 411 articles from Pubmed, 739 articles from Web of Science, 460 articles in Embase, 8 articles from Cochrane Library, 5 articles from references. Excluding the duplicates, unrelated topics, unoriginal clinical studies, non-English articles, and studies without original data, 19 full-text articles [3,12,17,19,[31][32][33][34][35][36][37][38][39][40][41][42][43][44] were assessed for possibly eligible. Finally, 9 studies [3,19,[32][33][34]37,39,41,44] were selected because of the eligibility for the systematic review and network meta-analysis.…”

ImmunoPET: Antibody-Based PET Imaging in Solid Tumors

“…The first clinical trial of pretargeted PET with TF2, a bispecific trivalent mAb of anti-CEA × anti-HSG, in relapsing MTC patients showed high tumor uptake ( 285 ). Moreover, the TF2 probe had superior sensitivity over [ 18 F]fluoro-l-dopa ([ 18 F]FDOPA) PET/CT ( 148 , 286 ) and CT ( 286 ) in detecting metastatic lesions.…”

Pretargeting: A Path Forward for Radioimmunotherapy

“…In the last 2 y, additional clinical studies with TF2/ 68 Ga-IMP288 were performed on CRC (113) and HER2-negative/CEA-positive metastatic breast cancer patients (114). In 2021, Bodet-Milin et al reported clinical data using TF2/ 68 Ga-IMP288 in MTC patients, demonstrating improved sensitivity for metastatic lesion detection over 18 F-L-dihydroxyphenylalanine PET/CT (115). Select examples of recent clinical PRID studies with TF2/IMP288 are shown in Figure 4.…”