Feasibility of 186Re-radioimmunotherapy for treatment in an adjuvant setting of colon cancer.
OBJECTIVE
(186)Re displays abundant intermediate energy beta emission, and possesses an appropriate physical half-life of 3.7 days. We compared the efficacy of radioimmunotherapy (RIT) with an anti-colorectal cancer monoclonal IgG1, (186)Re-A7, with that of RIT employing (131)I in a mouse liver metastasis model.


METHODS
Liver metastases were established by intrasplenic injection of LS180 human colon cancer cells. Based on the results of toxicity assessment with escalated administration doses, 21 MBq (186)Re-A7 and 7 MBq (131)I-A7 were chosen as maximum tolerated doses. In the first experiment, mice underwent RIT at 2 weeks when metastases attain a diameter of several millimeters, and were killed 2 weeks later to assess metastatic burden in the liver. In the second experiment, RIT was conducted at 1 week when metastases of several hundred micrometers in diameter were observed, and survival of mice was examined.


RESULTS
(186)Re-A7 RIT inhibited the growth of liver metastases better than (131)I-A7 RIT ( P<0.02). Furthermore, (186)Re-A7 RIT induced better improvement in survival of mice than (131)I-A7 RIT ( P<0.002). (186)Re-A7 RIT caused slightly more severe myelotoxicity in mice, but they eventually recovered. Radiation dose estimation demonstrated a significant advantage of (186)Re-A7 RIT over (131)I-A7 RIT.


CONCLUSIONS
These results support the use of RIT with (186)Re-MAb in an adjuvant setting in cases involving minimal disease.
Kinuya
Seigo
S
Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takaramachi, 920-8640, Kanazawa, Ishikawa, Japan.
Yokoyama
Kunihiko
K
Izumo
Mishiroku
M
Sorita
Takami
T
Obata
Takashi
T
Mori
Hirofumi
H
Shiba
Kazuhiro
K
Watanabe
Naoto
N
Shuke
Noriyuki
N
Michigishi
Takatoshi
T
Tonami
Norihisa
N
D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012211:Rhenium / Q000008:administration & dosage / Q000627:therapeutic use*
D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D012211:Rhenium