TY - JOUR
T1 - Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer
T2 - a phase I feasibility study
AU - Lamberts, Laetitia E
AU - Koch, Maximillian
AU - de Jong, Johannes S
AU - Adams, Arthur
AU - Glatz, Juergen
AU - Kranendonk, Marriette E G
AU - Terwisscha van Scheltinga, Anton G T
AU - Jansen, Liesbeth
AU - de Vries, Jakob
AU - Lub-de Hooge, Marjolijn N
AU - Schroder, Carolien P
AU - Jorritsma-Smit, Annelies
AU - Linssen, Matthijs D
AU - de Boer, Esther
AU - van der Vegt, Bert
AU - Nagengast, Wouter B
AU - Elias, Sjoerd G
AU - Oliveira, Sabrina
AU - Witkamp, Arjen
AU - Mali, Willem P Th M
AU - van der Wall, Elsken
AU - Van Diest, Paul J
AU - de Vries, Elisabeth G
AU - Ntziachristos, Vasilis
AU - van Dam, Gooitzen M
N1 - Copyright ©2017, American Association for Cancer Research.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - PURPOSE: to provide proof of principle of safety, breast tumor-specific uptake and positive tumor margin assessment of the systemically administered near-infrared fluorescent (NIRF) tracer bevacizumab-IRDye800CW targeting vascular endothelial growth factor (VEGF)-A in breast cancer patients.EXPERIMENTAL DESIGN: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and co-registration of tumor tissue and healthy tissue.RESULTS: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared to those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two out of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level.CONCLUSIONS: Our study shows that systemic administration of the bevacizumab-IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor-margin uptake as evaluated by a systematic validation methodology. The findings are a step towards a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in tumor tissue.
AB - PURPOSE: to provide proof of principle of safety, breast tumor-specific uptake and positive tumor margin assessment of the systemically administered near-infrared fluorescent (NIRF) tracer bevacizumab-IRDye800CW targeting vascular endothelial growth factor (VEGF)-A in breast cancer patients.EXPERIMENTAL DESIGN: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and co-registration of tumor tissue and healthy tissue.RESULTS: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared to those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two out of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level.CONCLUSIONS: Our study shows that systemic administration of the bevacizumab-IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor-margin uptake as evaluated by a systematic validation methodology. The findings are a step towards a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in tumor tissue.
U2 - 10.1158/1078-0432.CCR-16-0437
DO - 10.1158/1078-0432.CCR-16-0437
M3 - Article
C2 - 28119364
SN - 1078-0432
VL - 23
SP - 2730
EP - 2741
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -
