PT  - JOURNAL ARTICLE
AU  - Babs G Sibinga Mulder
AU  - Marjory Koller
AU  - Evelien W. Duiker
AU  - Arantza Farina Sarasqueta
AU  - Jakobus Burggraaf
AU  - Vincent E. de Meijer
AU  - Alex L Vahrmeijer
AU  - Frederik J.H. Hoogwater
AU  - Bert A. Bonsing
AU  - Gooitzen M. van Dam
AU  - Sven Mieog
AU  - Bobby K. Pranger
TI  - Intraoperative molecular fluorescence imaging of pancreatic cancer by targeting vascular endothelial growth factor: A multicenter feasibility dose-escalation study
AID  - 10.2967/jnumed.121.263773
DP  - 2022 Jun 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.121.263773
4099  - http://jnm.snmjournals.org/content/early/2022/06/09/jnumed.121.263773.short
4100  - http://jnm.snmjournals.org/content/early/2022/06/09/jnumed.121.263773.full
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.