Metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model is inhibited by neoadjuvant chemotherapy in combination with fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore

• Published in: PloS one 2014-12, Vol.9 (12), p.e114310-e114310
• Main Authors: Hiroshima, Yukihiko, Maawy, Ali, Zhang, Yong, Murakami, Takashi, Momiyama, Masashi, Mori, Ryutaro, Matsuyama, Ryusei, Katz, Matthew H G, Fleming, Jason B, Chishima, Takashi, Tanaka, Kuniya, Ichikawa, Yasushi, Endo, Itaru, Hoffman, Robert M, Bouvet, Michael
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Adenocarcinoma; Adjuvant chemotherapy; Animals; Antigens; Antineoplastic Agents - therapeutic use; Biopsy; CA-19-9 Antigen - immunology; Cancer patients; Cancer therapies; Chemotherapy; Chemotherapy, Adjuvant; Colorectal cancer; Combined Modality Therapy; Fluorescence; Fluorescent Dyes - chemistry; Gemcitabine; Heterografts; Humans; Medicine; Medicine and Health Sciences; Metastases; Metastasis; Mice; Mice, Nude; Neoplasm Metastasis; Ostomy; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Pancreaticoduodenectomy; Patients; Recurrence (Disease); Research and Analysis Methods; Surgery; Tumors; University graduates; Xenografts; Xenotransplantation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0114310

The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS+NAC; FGS only; and FGS+NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS had no benefit over BLS to prevent metastatic recurrence. NAC in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence.