TY - JOUR
T1 - Glypican-1 as a target for fluorescence molecular imaging of bladder cancer
AU - Polikarpov, Dmitry M.
AU - Campbell, Douglas H.
AU - Zaslavsky, Alexander B.
AU - Lund, Maria E.
AU - Wu, Angela
AU - Lu, Yanling
AU - Palapattu, Ganesh S.
AU - Walsh, Bradley J.
AU - Zvyagin, Andrei V.
AU - Gillatt, David A.
PY - 2021/12
Y1 - 2021/12
N2 - Objectives: To investigate whether anti-glypican-1 antibody Miltuximab conjugated with near-infrared dye IRDye800CW can be used for in vivo fluorescence imaging of urothelial carcinoma.Methods: The conjugate, Miltuximab-IRDye800CW, was produced and characterized by size exclusion chromatography and flow cytometry with glypican-1-expressing cells. Balb/c nude mice bearing subcutaneous urothelial carcinoma xenografts were intravenously injected with Miltuximab-IRDye800CW or control IgG-IRDye800CW and imaged daily by fluorescence imaging. After 10 days, tumors and major organs were collected for ex vivo study of the conjugate biodistribution, including its accumulation in the tumor.Results: The intravenous injection of Miltuximab-IRDye800CW to tumor-bearing mice showed its specific accumulation in the tumors with the tumor-to-background ratio of 12.7 ± 2.4, which was significantly higher than that in the control group (4.6 ± 0.9, P < 0.005). The ex vivo imaging was consistent with the in vivo findings, with tumors from the mice injected with Miltuximab-IRDye800CW being significantly brighter than the organs or the control tumors.Conclusions: The highly specific accumulation and retention of Miltuximab-IRDye800CW in glypican-1-expressing tumors in vivo shows its high potential for fluorescence imaging of urothelial carcinoma and warrants its further investigation toward clinical translation.
AB - Objectives: To investigate whether anti-glypican-1 antibody Miltuximab conjugated with near-infrared dye IRDye800CW can be used for in vivo fluorescence imaging of urothelial carcinoma.Methods: The conjugate, Miltuximab-IRDye800CW, was produced and characterized by size exclusion chromatography and flow cytometry with glypican-1-expressing cells. Balb/c nude mice bearing subcutaneous urothelial carcinoma xenografts were intravenously injected with Miltuximab-IRDye800CW or control IgG-IRDye800CW and imaged daily by fluorescence imaging. After 10 days, tumors and major organs were collected for ex vivo study of the conjugate biodistribution, including its accumulation in the tumor.Results: The intravenous injection of Miltuximab-IRDye800CW to tumor-bearing mice showed its specific accumulation in the tumors with the tumor-to-background ratio of 12.7 ± 2.4, which was significantly higher than that in the control group (4.6 ± 0.9, P < 0.005). The ex vivo imaging was consistent with the in vivo findings, with tumors from the mice injected with Miltuximab-IRDye800CW being significantly brighter than the organs or the control tumors.Conclusions: The highly specific accumulation and retention of Miltuximab-IRDye800CW in glypican-1-expressing tumors in vivo shows its high potential for fluorescence imaging of urothelial carcinoma and warrants its further investigation toward clinical translation.
KW - fluorescence-guided surgery
KW - glypican-1
KW - molecular imaging
KW - monoclonal antibodies
KW - urinary bladder neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85114455394&partnerID=8YFLogxK
U2 - 10.1111/iju.14683
DO - 10.1111/iju.14683
M3 - Article
C2 - 34498294
AN - SCOPUS:85114455394
SN - 0919-8172
VL - 28
SP - 1290
EP - 1297
JO - International Journal of Urology
JF - International Journal of Urology
IS - 12
ER -