Intraperitoneal radioimmunotherapy in treating peritoneal carcinomatosis of colon cancer in mice compared with systemic radioimmunotherapy.
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.
Kinuya
Seigo
S
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
Li
Xiao-Feng
XF
Yokoyama
Kunihiko
K
Mori
Hirofumi
H
Shiba
Kazuhiro
K
Watanabe
Naoto
N
Shuke
Noriyuki
N
Bunko
Hisashi
H
Michigishi
Takatoshi
T
Tonami
Norihisa
N
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