RT Journal Article
SR Electronic
T1 Fluorescence-Guided Visualization of Soft-Tissue Sarcomas by Targeting Vascular Endothelial Growth Factor A: A Phase 1 Single-Center Clinical Trial
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 342
OP 347
DO 10.2967/jnumed.120.245696
VO 62
IS 3
A1 Pieter J. Steinkamp
A1 Bobby K. Pranger
A1 Mei-Fang Li
A1 Matthijs D. Linssen
A1 Floris J. Voskuil
A1 Lukas B. Been
A1 Barbara L. van Leeuwen
A1 Albert J.H. Suurmeijer
A1 Wouter B. Nagengast
A1 Schelto Kruijff
A1 Robert J. van Ginkel
A1 Gooitzen M. van Dam
YR 2021
UL http://jnm.snmjournals.org/content/62/3/342.abstract
AB Resection of soft-tissue sarcoma (STS) is accompanied by a high rate of tumor-positive surgical margins (14%–34%), which potentially lead to decreased disease-free survival. Vascular endothelial growth factor A is overexpressed in malignant tumors, including STS, and can be targeted with bevacizumab-800CW during fluorescence-guided surgery for real-time tumor detection. In this phase 1 clinical trial, we determined the feasibility, safety, and optimal dose of bevacizumab-800CW for fluorescence-guided surgery in STS for in vivo and ex vivo tumor detection. Methods: Patients with a histopathologic diagnosis of STS were included. In the dose-escalation phase, patients received bevacizumab-800CW intravenously 3 d before surgery (10, 25, and 50 mg; n = 8). In the subsequent dose-expansion phase, 7 additional patients received bevacizumab-800CW at the optimal dose. Fluorescence images were obtained in vivo and ex vivo during all stages of standard care. The optimal dose was determined by calculating in vivo and ex vivo tumor-to-background ratios (TBR) and correlating these results with histopathology. Results: Fifteen patients with STS completed this study. All tumors could be visualized during in vivo and ex vivo imaging. The optimal bevacizumab-800CW dose proved to be 10 mg, with a median in vivo TBR of 2.0 (±0.58) and a median ex vivo TBR of 2.67 (±1.6). All 7 tumor-positive margins could be observed in real time after surgical resection. Conclusion: GS using 10 mg of bevacizumab-800CW is feasible and safe for intraoperative imaging of STS, potentially allowing tumor detection and margin assessment during surgery. An additional follow-up phase 2 study is needed to confirm the diagnostic accuracy.