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

Yukihiko Hiroshima, Ali Maawy, Cristina A. Metildi, Yong Zhang, Fuminari Uehara, Shinji Miwa, Shuuya Yano, Sho Sato, Takashi Murakami, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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. Materials and 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 prsent 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.

Original languageEnglish
Pages (from-to)241-247
Number of pages7
JournalJournal of Laparoendoscopic and Advanced Surgical Techniques
Volume24
Issue number4
DOIs
Publication statusPublished - Apr 1 2014
Externally publishedYes

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Carcinoembryonic Antigen
Heterografts
Colonic Neoplasms
Fluorescence
Antibodies
Neoplasms
Severe Combined Immunodeficiency
Optical Imaging
Laparotomy
Molecular Probes
Frozen Sections
Operating Rooms
Nude Mice
Microscopy
Colorectal Neoplasms
Colon
Hand
Clinical Trials
Technology
Light

ASJC Scopus subject areas

  • Surgery

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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. / Hiroshima, Yukihiko; Maawy, Ali; Metildi, Cristina A.; Zhang, Yong; Uehara, Fuminari; Miwa, Shinji; Yano, Shuuya; Sato, Sho; Murakami, Takashi; Momiyama, Masashi; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M.

In: Journal of Laparoendoscopic and Advanced Surgical Techniques, Vol. 24, No. 4, 01.04.2014, p. 241-247.

Research output: Contribution to journalArticle

Hiroshima, Y, Maawy, A, Metildi, CA, Zhang, Y, Uehara, F, Miwa, S, Yano, S, Sato, S, Murakami, T, Momiyama, M, Chishima, T, Tanaka, K, Bouvet, M, Endo, I & Hoffman, RM 2014, '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', Journal of Laparoendoscopic and Advanced Surgical Techniques, vol. 24, no. 4, pp. 241-247. https://doi.org/10.1089/lap.2013.0418
Hiroshima, Yukihiko ; Maawy, Ali ; Metildi, Cristina A. ; Zhang, Yong ; Uehara, Fuminari ; Miwa, Shinji ; Yano, Shuuya ; Sato, Sho ; Murakami, Takashi ; Momiyama, Masashi ; Chishima, Takashi ; Tanaka, Kuniya ; Bouvet, Michael ; Endo, Itaru ; Hoffman, Robert M. / 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. In: Journal of Laparoendoscopic and Advanced Surgical Techniques. 2014 ; Vol. 24, No. 4. pp. 241-247.
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abstract = "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. Materials and 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{\circledR} 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 prsent 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.",
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AU - Maawy, Ali

AU - Metildi, Cristina A.

AU - Zhang, Yong

AU - Uehara, Fuminari

AU - Miwa, Shinji

AU - Yano, Shuuya

AU - Sato, Sho

AU - Murakami, Takashi

AU - Momiyama, Masashi

AU - Chishima, Takashi

AU - Tanaka, Kuniya

AU - Bouvet, Michael

AU - Endo, Itaru

AU - Hoffman, Robert M.

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N2 - 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. Materials and 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 prsent 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.

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