TY - JOUR
T1 - Intraoperative molecular fluorescence imaging of pancreatic cancer by targeting vascular endothelial growth factor
T2 - A multicenter feasibility dose-escalation study
AU - Sibinga Mulder, Babs G
AU - Koller, Marjory
AU - Duiker, Evelien W
AU - Farina Sarasqueta, Arantza
AU - Burggraaf, Jakubus
AU - de Meijer, Vincent E
AU - Vahrmeijer, Alexander L
AU - Hoogwater, Frederik J H
AU - Bonsing, Bert A
AU - van Dam, Gooitzen M
AU - Mieog, Sven
AU - Pranger, Bobby K
N1 - Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2023/1
Y1 - 2023/1
N2 - Rationale: Tumor visualization with near-infrared fluorescence (NIRF) imaging could aid exploration and resection of pancreatic cancer by visualizing the tumor in real time. Conjugation of the near-infrared fluorophore IRDye800CW to the monoclonal antibody bevacizumab enables targeting of vascular endothelial growth factor-A (VEGF-A). The aim of this study was to determine if intraoperative tumor-specific imaging of pancreatic cancer with the fluorescent tracer bevacizumab-800CW is feasible and safe. Materials and Methods: In this multicenter, dose escalation phase I trial patients with suspicion of pancreatic ductal adenocarcinoma (PDAC) were administered bevacizumab-800CW (4.5mg, 10mg or 25mg) three days before surgery. Safety monitoring encompassed allergic or anaphylactic reactions and serious adverse events attributed to bevacizumab-800CW. Intraoperative NIRF imaging was performed immediately after laparotomy, just before and after resection of the specimen. Postoperatively, fluorescence signals on the axial slices and formalin-fixed paraffin-embedded tissue blocks from the resected specimens were correlated to histology. Subsequently, tumor-to-background ratios (TBR) were calculated. Results: Ten patients with clinically suspected PDAC were enrolled in the study. Four of the resected specimens were confirmed PDACs; other malignancies were distal cholangiocarcinoma, ampullary carcinoma and neuroendocrine tumors. No serious adverse events were related to bevacizumab-800CW. In vivo tumor visualization with NIRF imaging differed per tumor type and was non-conclusive. Ex vivo TBRs were 1.3, 1.5 and 2.5 for 4.5mg, 10mg and 25mg groups, respectively. Conclusion: NIRF guided surgery in patients with suspect PDAC using bevacizumab-IRDye800CW is feasible and safe. However, suboptimal TBRs were obtained because no clear distinction between pancreatic cancer from normal or inflamed pancreatic tissue was achieved. Therefore, a more tumor-specific tracer other than bevacizumab-IRDye800CW for PDAC is preferred.
AB - Rationale: Tumor visualization with near-infrared fluorescence (NIRF) imaging could aid exploration and resection of pancreatic cancer by visualizing the tumor in real time. Conjugation of the near-infrared fluorophore IRDye800CW to the monoclonal antibody bevacizumab enables targeting of vascular endothelial growth factor-A (VEGF-A). The aim of this study was to determine if intraoperative tumor-specific imaging of pancreatic cancer with the fluorescent tracer bevacizumab-800CW is feasible and safe. Materials and Methods: In this multicenter, dose escalation phase I trial patients with suspicion of pancreatic ductal adenocarcinoma (PDAC) were administered bevacizumab-800CW (4.5mg, 10mg or 25mg) three days before surgery. Safety monitoring encompassed allergic or anaphylactic reactions and serious adverse events attributed to bevacizumab-800CW. Intraoperative NIRF imaging was performed immediately after laparotomy, just before and after resection of the specimen. Postoperatively, fluorescence signals on the axial slices and formalin-fixed paraffin-embedded tissue blocks from the resected specimens were correlated to histology. Subsequently, tumor-to-background ratios (TBR) were calculated. Results: Ten patients with clinically suspected PDAC were enrolled in the study. Four of the resected specimens were confirmed PDACs; other malignancies were distal cholangiocarcinoma, ampullary carcinoma and neuroendocrine tumors. No serious adverse events were related to bevacizumab-800CW. In vivo tumor visualization with NIRF imaging differed per tumor type and was non-conclusive. Ex vivo TBRs were 1.3, 1.5 and 2.5 for 4.5mg, 10mg and 25mg groups, respectively. Conclusion: NIRF guided surgery in patients with suspect PDAC using bevacizumab-IRDye800CW is feasible and safe. However, suboptimal TBRs were obtained because no clear distinction between pancreatic cancer from normal or inflamed pancreatic tissue was achieved. Therefore, a more tumor-specific tracer other than bevacizumab-IRDye800CW for PDAC is preferred.
U2 - 10.2967/jnumed.121.263773
DO - 10.2967/jnumed.121.263773
M3 - Article
C2 - 35680414
SN - 0161-5505
VL - 64
SP - 82
EP - 89
JO - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
IS - 1
ER -