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; Zhang, Yong; Uehara, Fuminari; Miwa, Shinji; Yano, Shuya; Sato, Shigeo; Murakami, Takashi; Momiyama, Masashi; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M.

doi:10.1089/lap.2013.0418

Cited by 121 publications

(92 citation statements)

References 29 publications

(32 reference statements)

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“…The cumulative effects of PEGylation were to increase dye-conjugated anti-CEA antibody half-life, favorably alter the biodistribution, and significantly increase tumor to background contrast. PEGylated dyes conjugated to tumor-specific antibodies should have an important impact in the development of fluorescence guided surgery of cancer, 1,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] as these dyes offer the possibility of high fidelity-targeted tumor and metastases labeling.…”

Section: Tissue Biodistributionmentioning

confidence: 99%

Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

et al. 2014

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Abstract. Labeling of metastatic tumors can aid in their staging and resection of cancer. Near infrared (NIR) dyes have been used in the clinic for tumor labeling. However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph nodes, which hinders detection of metastasis. In order to overcome these problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude mice. Serum samples were collected at various time points in order to determine serum concentrations and elimination kinetics. Conjugated PEGylated dyes had significantly higher serum dye concentrations than non-PEGylated dyes (p ¼ 0.005 for the 650 dyes and p < 0.001 for the 750 dyes). Human pancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with conjugated PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (p < 0.001 for the 650 dyes; p ¼ 0.01 for 750 dyes). PEGylation of the NIR dyes also decreased their accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific antibody, suggesting their future clinical use in fluorescence-guided surgery.

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Section: Tissue Biodistributionmentioning

confidence: 99%

Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

et al. 2014

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“…Toward the goal of precision oncology, our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI), including pancreatic, [1][2][3][4] breast, 5 ovarian, 6 lung, 7 cervical, 8 colon, [9][10][11] and stomach cancer, 12 sarcoma, [13][14][15][16][17] and melanoma. [18][19][20] In a previous study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared with cisplatinum (CDDP) on a lung-metastatic osteosarcoma PDOX mouse model.…”

Section: Introductionmentioning

confidence: 99%

Intra-arterial administration of tumor-targetingSalmonella typhimuriumA1-R regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

et al. 2017

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Previously, a patient-derived orthotopic xenograft (PDOX) model was established with a lung metastasis from an osteosarcoma patient which developed after adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared with CDDP. In the present report, osteosarcoma tissue was implanted orthotopically in the distal femur of mice which were randomized into the following groups when tumor volume reached approximately 100 mm 3 ; On day 14 after initiation of treatment, all but CDDP significantly inhibited tumor volume growth compared with untreated controls. Control (G1

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“…PDOX models, which were implanted using intact tumor tissue with the technique of surgical orthotopic implantation (SOI) (25,27), were established from patients with colonic (28)(29)(30), pancreatic (21, 31-41), breast (42), ovarian (43), lung (44), and stomach cancer (45), and mesothelioma (46) in the early 1990s, resulting in primary and metastatic tumor growth very similar to that in the patient.…”

Section: Patient-derived Orthotopic Xenograft (Pdox) Mouse Models Of mentioning

confidence: 99%

Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse Models of Cancer

Suetsugu

Shimizu

Saji

et al. 2018

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Abstract. The tumor microenvironment (TME) contains stromal cells in a complex interaction with cancer cells. This relationship has become better understood with the use of fluorescent proteins for in vivo imaging cancer-cell or stromal-cell targeting by potential therapeutics can be visualized. Color-coded imaging enabled the visualization of apparent fusion of cancer and stromal cells. Color-coded imaging is a powerful tool visualizing the interaction of cancer and stromal cells during cancer progression and treatment.In vivo imaging with fluorescent proteins was pioneered by our laboratories and has been particularly useful for studying tumor growth, invasion, cancer-cell trafficking, metastasis, angiogenesis, and other aspects of tumor progression (1-5). Multicolored proteins have allowed the color-coding of cancer cells growing in vivo such as between highly-and poorly-metastatic cells, cancer stem and non-stem cells, and gene transfer between cancer cells (3, 4,(6)(7)(8)(9)(10)(11)(12)(13).The present review focuses on color-coded imaging of cancer and stromal cells in the tumor microenvironment (TME).Transgenic nude mice expressing fluorescent proteins for colorcode imaging of the TME. The green fluorescent protein (GFP)-expressing athymic nude mouse was obtained by crossing nontransgenic nude mice with the transgenic C57/B6 GFP mouse in which the β-actin promoter drives GFP. In the adult GFP nude mice, most organs brightly expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, duodenum, and the entire digestive system from the tongue to the anus; the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The bared skeleton also highly expressed GFP (14).

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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

Abstract: 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.

Cited by 121 publications

References 29 publications

Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

Intra-arterial administration of tumor-targetingSalmonella typhimuriumA1-R regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse Models of Cancer

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