Tumor paint: a chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci.
Toward the goal of developing an optical imaging contrast agent that will enable surgeons to intraoperatively distinguish cancer foci from adjacent normal tissue, we developed a chlorotoxin:Cy5.5 (CTX:Cy5.5) bioconjugate that emits near-IR fluorescent signal. The probe delineates malignant glioma, medulloblastoma, prostate cancer, intestinal cancer, and sarcoma from adjacent non-neoplastic tissue in mouse models. Metastatic cancer foci as small as a few hundred cells were detected in lymph channels. Specific binding to cancer cells is facilitated by matrix metalloproteinase-2 (MMP-2) as evidenced by reduction of CTX:Cy5.5 binding in vitro and in vivo by a pharmacologic blocker of MMP-2 and induction of CTX:Cy5.5 binding in MCF-7 cells following transfection with a plasmid encoding MMP-2. Mouse studies revealed that CTX:Cy5.5 has favorable biodistribution and toxicity profiles. These studies show that CTX:Cy5.5 has the potential to fundamentally improve intraoperative detection and resection of malignancies.
Veiseh
Mandana
M
Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
Gabikian
Patrik
P
Bahrami
S-Bahram
SB
Veiseh
Omid
O
Zhang
Miqin
M
Hackman
Robert C
RC
Ravanpay
Ali C
AC
Stroud
Mark R
MR
Kusuma
Yumiko
Y
Hansen
Stacey J
SJ
Kwok
Deborah
D
Munoz
Nina M
NM
Sze
Raymond W
RW
Grady
William M
WM
Greenberg
Norman M
NM
Ellenbogen
Richard G
RG
Olson
James M
JM
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D005910:Glioma / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D009369:Neoplasms / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D017785:Photons; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry*
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D012604:Scorpion Venoms; C091539:Chlorotoxin; D020778:Matrix Metalloproteinase 2