title: Photoimmunotherapy lowers recurrence after pancreatic cancer surgery in orthotopic nude mouse models.
abstract: BACKGROUND
  Photoimmunotherapy (PIT) is based on the use of a monoclonal antibody specific to cancer epitopes conjugated to a photosensitizer near-infrared phthalocyanine dye (IR700). In this study, PIT with IR700 conjugated to anti-carcinoembryonic antigen (CEA) was used as an adjunct to surgery in orthotopically-implanted human pancreatic cancer in a nude mouse model to eliminate microscopic disease in the post-surgical tumor bed and prevent local as well as metastatic recurrence.
  
  
  METHODS
  Athymic nude mice were orthotopically implanted with the human pancreatic cancer cell line BxPC3 expressing green fluorescent protein. After tumor engraftment, the mice were divided into two groups as follows: bright light surgery (BLS) + anti-CEA-IR700 + 690 nm laser (PIT); and BLS only. Anti-CEA-IR700 (100 μg) was administered to the treatment group via tail-vein injection 24 h before therapy. Tumors were resected, and the surgical bed was treated with intraoperative phototherapy at an intensity of 150 mW/cm(2) for 30 min. Mice were imaged noninvasively for 8 wk using an OV-100 small animal fluorescence imager.
  
  
  RESULTS
  BLS + PIT reduced local recurrence to 1/7 mice from 7/7 mice with BLS-only (P = 0.001) and metastatic recurrence to 2/7 mice compared with 6/7 mice with BLS-only (P = 0.03). Local tumor growth continued at a rapid rate after BLS-only compared with BLS + PIT where almost no local growth occurred. There was a significant difference in tumor size between mice in the BLS + PIT (2.14 mm(2), 95% confidence interval [CI] [-2.06 to 6.34] and BLS-only groups (115.2 mm(2), 95% CI [88.8-141.6]) at 6 wk after surgery (P < 0.001). There was also a significant difference in tumor weight between the BLS + PIT group (6.65 mg, 95% CI [-6.35 to 19.65] and BLS-only group (1100 mg, 95% CI [794-1406] at 8 wk after surgery (P < 0.001).
  
  
  CONCLUSIONS
  PIT holds promise in the treatment of pancreatic cancer and may serve as a useful adjunct to surgery in the eradication of microscopic residual disease that can lead to both local and metastatic recurrence. Further studies are warranted to investigate the potential toxicities of PIT, especially with regard to anastomoses, such as those involved in pancreaticoduodenectomy.
authors: Department of Surgery, University of California San Diego, San Diego, California.
authors: Ali A
authors: AA
authors: Maawy
authors: Department of Surgery, University of California San Diego, San Diego, California; AntiCancer, Inc, San Diego, California; Department of Surgery, Yokohama City University, Yokohama City, Japan.
authors: Yukihiko
authors: Y
authors: Hiroshima
authors: AntiCancer, Inc, San Diego, California.
authors: Yong
authors: Y
authors: Zhang
authors: Aspyrian Therapeutics, San Diego, California.
authors: Miguel
authors: M
authors: Garcia-Guzman
authors: OncoFluor, Inc, San Diego, California.
authors: George A
authors: GA
authors: Luiken
authors: National Institutes of Health, Bethesda, Maryland.
authors: Hisataka
authors: H
authors: Kobayashi
authors: Department of Surgery, University of California San Diego, San Diego, California; AntiCancer, Inc, San Diego, California.
authors: Robert M
authors: RM
authors: Hoffman
authors: Department of Surgery, University of California San Diego, San Diego, California; Department of Surgery, VA Healthcare System, San Diego, California. Electronic address: mbouvet@ucsd.edu.
authors: Michael
authors: M
authors: Bouvet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D054833:Isoindoles; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; C013647:phthalocyanine
keywords: CEA; Orthotopic mouse models; Pancreatic cancer; Photoimmunotherapy; Surgery