Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system.
BACKGROUND
Fluorescence-guided surgery (FGS) can enable successful cancer surgery where bright-light surgery often cannot. There are three important issues for FGS going forward toward the clinic: (a) proper tumor labeling, (b) a simple portable imaging system for the operating room, and (c) patient-like mouse models in which to develop the technology. The present report addresses all three.


METHODS
Patient colon tumors were initially established subcutaneously in nonobese diabetic (NOD)/severe combined immune deficiency (SCID) mice immediately after surgery. The tumors were then harvested from NOD/SCID mice and passed orthotopically in nude mice to make patient-derived orthotopic xenograft (PDOX) models. Eight weeks after orthotopic implantation, a monoclonal anti-carcinoembryonic antigen (CEA) antibody conjugated with AlexaFluor 488 (Molecular Probes Inc., Eugene, OR) was delivered to the PDOX models as a single intravenous dose 24 hours before laparotomy. A hand-held portable fluorescence imaging device was used.


RESULTS
The primary tumor was clearly visible at laparotomy with the portable fluorescence imaging system. Frozen section microscopy of the resected specimen demonstrated that the anti-CEA antibody selectively labeled cancer cells in the colon cancer PDOX. The tumor was completely resected under fluorescence navigation. Histologic evaluation of the resected specimen demonstrated that cancer cells were not present in the margins, indicating successful tumor resection. The FGS animals remained tumor free for over 6 months.


CONCLUSIONS
The results of the present report indicate that FGS using a fluorophore-conjugated anti-CEA antibody and portable imaging system improves efficacy of resection for CEA-positive colorectal cancer. These data provide the basis for clinical trials.
1 AntiCancer, Inc. , San Diego, California.
Yukihiko
Y
Hiroshima
Ali
A
Maawy
Cristina A
CA
Metildi
Yong
Y
Zhang
Fuminari
F
Uehara
Shinji
S
Miwa
Shuya
S
Yano
Sho
S
Sato
Takashi
T
Murakami
Masashi
M
Momiyama
Takashi
T
Chishima
Kuniya
K
Tanaka
Michael
M
Bouvet
Itaru
I
Endo
Robert M
RM
Hoffman
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D002272:Carcinoembryonic Antigen / Q000276:immunology; D003110:Colonic Neoplasms / Q000473:pathology* / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006834:Hydrazines; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D061848:Optical Imaging / Q000379:methods*; D025321:Surgery, Computer-Assisted / Q000379:methods*; D014183:Transplantation, Heterologous
C417561:Alexa 488 hydrazide; D000888:Antibodies, Anti-Idiotypic; D002272:Carcinoembryonic Antigen; D006834:Hydrazines