title: Intraperitoneal radioimmunotherapy in treating peritoneal carcinomatosis of colon cancer in mice compared with systemic radioimmunotherapy.
abstract: Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current investigation, the efficacy of radioimmunotherapy (RIT) with i.p. administration of an anti-colorectal cancer IgG1, 131I-A7, was compared to that with i.v. administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131I-A7 and i.p. administered irrelevant 131I-HPMS-1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long-term survival: untreated mice (n = 11), mice undergoing i.p. RIT with 131I-A7 (n = 11), mice undergoing i.v. RIT with 131I-A7 (n = 11) and mice undergoing non-specific i.p. RIT with 131I-HPMS-1 (n = 5). Intraperitoneal injection of 131I-A7 produced faster and greater tumor accumulation than i.v. injection: 34.2 +/- 16.5% of the injected dose per g (% ID/g) and 11.1 +/- 3.6% ID/g at 2 h, respectively (P < 0.0001). Consequently, cumulative radioactivity in tumors was 1.73-fold higher with i.p. injection. 131I-HPMS-1 did not show specific accumulation. Non-specific RIT with 131I-HPMS-1 (mean survival, 26.0 +/- 2.5 days) did not affect the survival as compared to no treatment (26.7 +/- 1.9 days). Intravenous RIT with 131I-A7 prolonged the survival of mice to 32.8 +/- 1.8 days (P < 0.01). Intraperitoneal RIT with 131I-A7 improved the survival more significantly and attained cure in 2 of 11 mice (P < 0.05 vs. i.v. RIT). In conclusion, i.p. RIT is more beneficial in treating peritoneal carcinomatosis of colon cancer than i.v. RIT in a murine model.
authors.affiliation: Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Radioisotope Center, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan. kinuya@med.kanazawa-u.ac.jp
authors.forename: Seigo
authors.initials: S
authors.lastname: Kinuya
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mori
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
authors.forename: Naoto
authors.initials: N
authors.lastname: Watanabe
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shuke
authors.forename: Hisashi
authors.initials: H
authors.lastname: Bunko
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Michigishi
authors.forename: Norihisa
authors.initials: N
authors.lastname: Tonami
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D010534:Peritoneal Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D010976:Platelet Count; D016499:Radioimmunotherapy / Q000379:methods*; D016019:Survival Analysis; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015431:Weight Loss / Q000528:radiation effects