title: Radioimmunotherapy with 186Re-labeled monoclonal antibody to treat liver metastases of colon cancer cells in nude mice.
abstract: The efficacy of radioimmunotherapy (RIT) in the treatment of minimal disease has been previously shown, despite the limitation of beta-emitters suggested by a mathematical model. In the present study, the efficacy of RIT with an anti-colorectal cancer IgG1 A7 conjugated with 186Re was examined in a liver metastasis model established by intrasplenic inoculation of human colon cancer cells. In this model, small metastases of less than 1 mm in diameter can be observed 1 week after cell inoculation. Metastases attain a diameter of several millimeters at 2 weeks. 186Re-A7 accumulated exclusively in metastases, displaying a value of 24.1 +/- 8.7% ID/g 2 days after the injection. 186Re-A7 accumulation in liver metastases increased with decreasing size. RIT with 7 MBq 186Re-A7 at 2 weeks significantly suppressed the growth of metastases; weight of metastases 4 weeks after cell inoculation was 5.96 +/- 0.87 g in nontreated control mice and 1.25 +/- 0.75 g in mice receiving 186Re-A7 RIT (p < 0.0001). RIT at 1 week more effectively inhibited metastatic growth to 0.08 +/- 0.05 g (p < 0.002 vs. RIT at 2 weeks). RIT with a class-matched irrelevant MAb 186Re-HPMS-1 at 1 week after cell inoculation somewhat suppressed metastatic growth, 3.39 +/- 0.25 g at 4 weeks, as compared with the control; however, 186Re-HPMS-1 RIT was far less effective than 186Re-A7 RIT (p < 0.0001). These results support the use of RIT with 186Re-MAb in an adjuvant setting in cases involving minimal disease. Factors such as higher and homogeneous MAb accumulation in small nodules, better perfusion, and subsequent better oxygenation likely compensate for the loss of beta radiation outside small metastases.
authors.affiliation: Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan. kinuya@med.kanazawa-u.ac.jp
authors.forename: Seigo
authors.initials: S
authors.lastname: Kinuya
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kawashima
authors.forename: Mishiroku
authors.initials: M
authors.lastname: Izumo
authors.forename: Takami
authors.initials: T
authors.lastname: Sorita
authors.forename: Takashi
authors.initials: T
authors.lastname: Obata
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; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D012211:Rhenium / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D012211:Rhenium